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Enrollment Starts in Randomized Phase II Panc Trial
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-prnews-1781272559.html?x=0&.v=20
Oncolytics Biotech® Inc. Announces Start of Enrollment in Randomized Phase II Pancreatic Cancer Study
Press Release Source: Oncolytics Biotech Inc. On Wednesday February 16, 2011, 7:30 am EST
CALGARY, Feb. 16 /PRNewswire-FirstCall/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC.to - News) announced today that enrollment has begun in a 2-Arm randomized Phase II study of carboplatin, paclitaxel plus REOLYSIN® versus carboplatin and paclitaxel alone in the first line treatment of patients with recurrent or metastatic pancreatic cancer. The Principal Investigator is Dr. Tanios Bekaii-Saab, Medical Director of Gastrointestinal Oncology at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. The Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, is sponsoring the trial under its Clinical Trials Agreement with Oncolytics, while Oncolytics will provide clinical supplies of REOLYSIN.
"Pancreatic cancer has seen very little progress over the last few decades," said Dr. Tanios Bekaii-Saab, principal investigator. "This clinical trial will allow us to evaluate a promising new treatment for pancreatic cancer with the goal of improving long-term survival for patients who typically have a poor prognosis."
The study is an open-label, multi-institution, 2-Arm Phase II randomized study of patients with metastatic pancreatic cancer. Patients will be randomized to receive either carboplatin, paclitaxel plus REOLYSIN (Arm A) or carboplatin and paclitaxel alone (Arm B). Patients in both arms will receive treatment every three weeks (21-day cycles). Patients in both arms will be receiving standard intravenous doses of paclitaxel and carboplatin on day one only. In Arm A, patients will also receive intravenous REOLYSIN at a dose of 3x1010 TCID50 on days one through five. Tumor response assessment will be done by CT scan and conducted every eight weeks. Patients that progress on carboplatin and paclitaxel (Arm B) will have REOLYSIN added. If patients experience significant toxicity related to carboplatin and/or paclitaxel they may continue with single agent REOLYSIN.
The primary objective of the trial is to assess improvement in progression-free survival with REOLYSIN, carboplatin and paclitaxel relative to carboplatin and paclitaxel alone in patients with metastatic pancreatic cancer. The primary endpoint is progression free survival in both arms. Secondary endpoints include overall response rate and overall survival. The study is expected to enroll approximately 70 patients.
About Pancreatic Cancer
The American Cancer Society estimates that 43,140 Americans were diagnosed with pancreatic cancer and an estimated 36,800 Americans were expected to die from the disease in 2010. The prognosis for patients diagnosed with pancreatic cancer, regardless of stage, is generally poor; the relative five-year survival rate for all stages combined is approximately 6%.
About The Ohio State University Comprehensive Cancer Center
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
About the NCI
The U.S. National Cancer Institute (NCI) is part of the National Institutes of Health and the U.S. Department of Health and Human Services. NCI's main responsibilities include coordinating the National Cancer Program; conducting and supporting cancer-related research; training physicians and scientists; and disseminating state-of-the-art information about cancer detection, diagnosis, treatment, prevention, control, palliative care, and survivorship.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Oncolytics at BIO CEO & Investor Conference
To be webcast
http://www.integratir.com/newsrelease.asp?news=2131024284&ticker=T.ONC&lang=EN
CALGARY, AB, February 10, 2011 --- Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX: ONC, NASDAQ: ONCY), will present a corporate overview of the Company at the 13th Annual BIO CEO & Investor Conference on Monday, February 14th, 2011 at 4:00 p.m. ET. Hosted by the Biotechnology Industry Organization (BIO), the 13th Annual CEO & Investor Conference will take place February 14th and 15th at the Waldorf-Astoria Hotel in New York.
A live audio link to the webcast presentation is available at:
http://www.veracast.com/webcasts/bio/ceoinvestor2011/61114431.cfm
, or on the company's website at www.oncolyticsbiotech.com. It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
About the BIO CEO and Investor Conference
Now in its thirteenth year, the BIO CEO & Investor Conference 2011 is the largest independent investor conference focused on publicly-traded biotechnology companies. Each year the BIO CEO & Investor Conference provides a neutral forum where institutional investors, industry analysts, and senior biotechnology executives have the opportunity to shape the future investment landscape of the biotechnology industry. The conference features issue-oriented plenary sessions, educational sessions focused on hot therapeutic areas and key business issues, company presentations, one-on-one meetings, and networking opportunities. For more information, visit http://www.bio.org/bioceo.
FOR FURTHER INFORMATION PLEASE CONTACT:
The Equicom Group
Nick Hurst
300 5th Ave. SW, 10th Floor
Calgary, Alberta T2P 3C4
Tel: 403.218.2835
Fax: 403.218.2830
nhurst@equicomgroup.com
The Investor Relations Group
Erika Moran
11 Stone St, 3rd Floor
New York, NY 10004
Tel: 212.825.3210
Fax: 212.825.3229
emoran@investorrelationsgroup.com
Pediatric Blood/Cancer: Oncolytic Virotherapy reaches Adolescence
http://onlinelibrary.wiley.com/doi/10.1002/pbc.22724/full
http://solvingkidscancer.org/fileread?t=project_articles&i=8
Scientific field review including Jennerex, Biovex and Oncolytics
Abstract
Lytic viruses kill cells as a consequence of their normal replication life cycle. The idea of harnessing viruses to kill cancer cells arose over a century ago, before viruses were even discovered, from medical case reports of infections associated with cancer remissions. Since then, there has been no shortage of hype, hope, or fear regarding the prospect of oncolytic virotherapy for cancer. Early developments in the field included encouraging antitumor efficacy both in animal studies in the 1920s–1940s and in human clinical trials in the 1950s–1970s. Despite its long-standing history, oncolytic virotherapy was an idea ahead of its time. Without needed advances in molecular biology, virology, immunology, and clinical research ethics, early clinical trials resulted in infectious complications and were fraught with controversial research conduct, so that enthusiasm in the medical community waned. Oncolytic virotherapy is now experiencing a major growth spurt, having sustained numerous laboratory advances and undergone multiple encouraging adult clinical trials, and is now witnessing the emergence of pediatric trials. Here we review the history and salient biology of the field, including preclinical and clinical data, with a special emphasis on those agents now being tested in pediatric cancer patients. Pediatric Blood Cancer. 2010;55:1253–1263. © 2010 Wiley-Liss, Inc.
Molecular Therapy Editorial on Oncolytic Viruses and Reolysin
Oncolytic Viruses: An Approved Product on the Horizon?
http://www.nature.com/mt/journal/v18/n2/full/mt2009314a.html
Editorial
Molecular Therapy (2010) 18 2, 233–234. doi:10.1038/mt.2009.314
John Bell
Associate Editor
Looking back over the past 15 years of oncolytic virus (OV) research, I cannot help being impressed by the creativity, ingenuity, and passion of those committed to seeing this platform succeed. Clever ideas that have led to novel targeting strategies, deciphering and exploitation of host–virus interactions, and innovative ways to deliver viruses to tumor beds are only a few of the basic science discoveries that have fueled excitement in the field.1,2,3 However, just as in professional sports where “winning is everything,” all that really matters in the end is what happens in the clinic. OVs captured the imagination of the scientific community, the public, and, perhaps unfortunately, even Hollywood—lest we forget “I Am Legend.” The excitement of being able to create miniature biological machines that can specifically target and kill tumor cells while leaving normal tissues unscathed perhaps raised unrealistic expectations about how rapidly these therapeutics could be implemented in the clinic. In reality, our ability to generate new and exciting replicating virus–based therapeutics has rapidly outstripped the resources available to test them in the clinic in a timely fashion. Indeed, what has continued to fuel the skepticism that OVs will ever be more than an interesting academic exercise has been the paucity of clinical activity in early-phase trials.
In a recent review, Ivy et al. pointed out that more than 44 small-molecule inhibitors of vascular endothelial growth factor receptor signaling are in development—many in phase III studies.4 Will we ever see the day when 44 OVs are in clinical development? Unlikely. There are tremendous differences between these therapeutic platforms, perhaps the most important being the complexity of the biological interactions between the virus and the patient. Steve Russell, Eva Galanis, and colleagues at the Mayo Clinic have developed a model for OV development that takes into account the challenges of developing a complex biological agent. They have created infrastructure “in house” that allows them to develop and control their therapeutics at the earliest stages when the platform is most vulnerable and requires nurturing in terms of engineering, manufacturing, and clinical testing. Their approach is to develop, in the academic setting, multiple viral products through at least phase I and possibly early phase II testing. The products that show safety, signs of efficacy, and/or targeting will be passed off to an industrial partner(s) for the pivotal trials.
Phase III studies are not for the faint of heart—they are expensive, time-consuming, and, if negative, can spell the end of a promising therapeutic. The OV field needs a winner, and three companies have compelling phase II data that they believe justifies carrying their products into phase III. The Biovex product OncoVEXGM-CSF (herpesvirus-expressing granulocyte macrophage-colony-stimulating factor) had a 26% objective response rate in a phase II trial of malignant melanoma patients. Particularly encouraging were responses at both injected and distant tumor sites, including visceral lesions, implying that there was systemic activity.5 Biovex has now entered an international phase III study under the US Food and Drug Administration (FDA) Special Protocol Assessment process for patients with stage III and IV malignant melanoma.
Oncolytics Biotech has been developing Reolysin (reovirus type III) for more than a decade, sponsoring 10 clinical trials designed to test safety and efficacy in a variety of indications and routes of administration. Recently, Hardev Pandha, Kevin Harrington, and Alan Melcher have championed this platform at both the preclinical and clinical levels.6,7 Pandha reports that their work demonstrates that “multi-dosing with Reolysin in an outpatient setting is both safe and feasible, results in minimal shedding and despite high seropositivity to reovirus in the community we have observed significant antitumor effects.” Oncolytics Biotech has obtained from the FDA a Special Protocol Assessment to conduct a phase III trial testing intravenous administration of reovirus in combination with paclitaxel and carboplatin in patients with head and neck cancer.
David Kirn, the chief executive officer of Jennerex Biotherapeutics, has “seen it all,” having been responsible for the clinical testing of the adenovirus Onyx-015 and been a longtime champion of the OV platform. His company is focusing on the development of vaccinia virus–based therapeutics, with the lead product, JX-594, showing exciting systemic responses in phase I trials in a spectrum of solid tumors and in phase II trials in hepatocellular carcinoma.8 James Burke, a key investigator in the Jennerex trials, is particularly excited about the potential of activating antitumor immunity in patients during oncolysis. According to Burke, “JX 594—and armed OV therapies in general—represent an opportunity to further harness the immune system to fight cancer. Perhaps more important than direct anticancer oncolysis, these viruses may allow the creation of autologous cancer vaccines in vivo—eliminating the costly, time-consuming, and labor-intensive method of creating cancer vaccine ex vivo—not to mention the possibility of increased relevance immunologically and in terms of activity.”
Jennerex plans to initiate phase III trials in liver cancer in 2010. Kirn feels confident that the OV field has reached a watershed moment in its development: “The history of oncolytic viruses in the clinic to date has demonstrated the safety, mechanism of action of our therapeutics and made those of us in the field true believers. However, for the greater oncology community to embrace this technology and initiate sustained investment in this platform, we require positive phase III results. Now, more than ever, a successful OV pivotal trial seems to be within our grasp.”
Oncolytic virotherapy is undergoing promising new research as a cancer treatment strategy, especially in conjunction with established therapies such as radiation. The ability of intravenously delivered oncolytic viruses to express antitumor genes, as well as to directly destroy cancer cells, makes them potentially effective against malignant cancers, although efficacy in humans is currently still limited.
Amgen Makes Bet on Viral Skin Cancer Killer
by Adam Feurstein 1/26/11 - 10:51 AM EST
http://www.thestreet.com/story/10985935/2/amgen-makes-bet-on-viral-skin-cancer-killer.html
THOUSAND OAKS, Calif. (TheStreet) -- When most people make long-shot bets, let's say playing the lottery when the jackpot hits $300 million, slapping down $5 doesn't seem like too big of a wager for what could be a fantastic payday.
When Amgen(AMGN_), likewise, decides to take a flyer, the biotech giant wagers $425 million. That may seem like a lot of money to place on a bet, and it surely is, but then, Amgen's wallet is stuffed with $17 billion.
Amgen's acquisition of privately held BioVex Group for $425 million upfront (plus another $575 million in potential future payments) announced Monday is a high-risk bet on a technology that seeks to re-engineer the simple herpes virus into an tumor-killing cancer immunotherapy. Right now, the only approved cancer immunotherapy is Dendreon's(DNDN_) prostate cancer treatment Provenge.
If the BioVex drug works, Amgen's investment will pay for itself because the company will control a novel drug with blockbuster potential as a treatment for skin cancer, but also perhaps head-and-neck and other solid tumor cancers. If BioVex blows up, Amgen wagered and lost less than 3% of its net cash.
Amgen and its shareholders don't need to wait very long for the BioVex bet to read out. The BioVex drug, known as OncoVex, is nearly through a pivotal phase III study in skin cancer with results expected in the second half of the year. A second phase III study in head-and-neck cancer is also underway.
In a phone interview Tuesday, Amgen's top scientist Roger Perlmutter acknowledged buying BioVex is a surprising and somewhat risky move for Amgen, especially given skepticism he's expressed publicly about cancer immunotherapy in general.
Why is BioVex any different?
"What impresses me about about BioVex is the firm scientific approach the company has taken in engineering the virus but also the responses seen to date [in clinical trials]," said Perlmutter, who oversees Amgen's entire research and development team. Amgen spent $2.9 billion on R&D last year.
OncoVex is an oncolytic (cancer-killing) virus that started as a simple herpes virus (the kind that causes cold sores) but was genetically re-engineered in the lab to seek out and invade fast-growing cancer cells. The virus is designed to leave healthy cells, which don't divide as fast, alone.
Once OncoVex invades a cancer cell, it does what viruses typically do, hijack the cell's replication mechanics and starts making lots and lots of copies of itself. All these viral copies cause the cancer cell to burst and die.
On its own, this cell-bursting technique isn't enough to turn OncoVex into a viable cancer treatment, so BioVex scientists made two other alterations to the herpes virus used to create OncoVex.
First, a gene was removed from the virus that typically makes it invisible to a patient's immune system. With that gene gone, a patient's immune system is alerted when OncoVex starts replicating and bursting cancer cells.
Second, a gene was inserted into the virus to produce a protein called GM-CSF that puts the immune system into a state of high alert. Now, immune system can more easily find the modified herpes virus (OncoVex) inside tumor cells and mount a vigorous attack.
Doctors inject OncoVex directly into tumors unlike most cancer drugs that are administered orally (as a pill) or intravenously into a vein. Perlmutter says BioVex wouldn't have been worth Amgen's investment if OncoVex proved capable of only eliminating tumors via direct injection. The tumor burden in advanced cancer patients, especially those with skin cancer, is too great to treat them effectively.
OncoVex, however, appears to activate a patient's immune system enough to target and eliminate tumors that are not directed injected. This so-called off-target or systemic response is what grabbed Perlmutter's attention and ultimately led to Amgen's decision to acquire BioVex.
"You can't make up these data. We are seeing tumor masses disappear that were not injected," he said.
In a phase II study that enrolled 50 patients with advanced skin cancer, treatment with OncoVex led to a 26% response rate, including eight patients with complete response (total elimination) of their cancer. Twelve of the 13 objective responses lasted for more than 6 months and the one-year survival rate for all patients was 58%. [That compares to a one-year survival rate of 25% from a meta-analysis of 2,100 skin cancer patients in 42 phase II trials.]
The OncoVex phase II study was presented at the American Society of Clinical Oncology annual meeting in June 2009 and published in the Journal of Clinical Oncology in December 2009
Yet Perlmutter, while excited about the prospects for OncoVex, concedes that the phase II study was small and may not presage positive results from the phase III study.
"We all know that phase II data imperfectly predict what will happen in phase III," he says. Skin cancer case histories, in particular, are rife with patients whose tumors spontaneously disappear, so OncoVex's efficacy won't be proven until data from the phase III study is compiled, Perlmutter added.
That phase III study is nearly fully enrolled with 360 advanced skin cancer patients who are being treated with either OncoVex or GM-CSF. The study's primary endpoint is durable objective response (maintained for at least six months.)
Results are expected later this year, at which time we'll know if Amgen picked a winning lottery ticket.
One more note: Oncolytics Biotech(ONCY_), an independent drug company not affiliated at all with Amgen but which is developing its own cancer-killing viral-based vaccine, may also benefit as investors seek an ancillary stock play should the OncoVex skin study read out positive.
--Written by Adam Feuerstein in Boston.
Oncolytic Virus News - Amgen buys BioVex
http://finance.yahoo.com/news/Amgen-4Q-profit-rises-buys-apf-1108339579.html?x=0&sec=topStories&pos=4&asset=&ccode=
Purchase price could reach $1Billion
This bodes very well for ONCY IMO.
May be a stock to watch the rest of this week. ONCY market cap is currently at $400 Million.
Amgen buys BioVex for up to $1 Billion
http://finance.yahoo.com/news/Amgen-to-Acquire-BioVex-a-prnews-4121962722.html?x=0&.v=1
Acquisition Includes a Therapeutic in Phase 3 Clinical Trials for the Treatment of Advanced Melanoma and Head and Neck Cancer
THOUSAND OAKS, Calif. and WOBURN, Mass., Jan. 24, 2011 /PRNewswire/ -- Amgen (Nasdaq:AMGN - News) and Group, Inc. today announced that the companies have entered into a definitive acquisition agreement under which Amgen has agreed to acquire BioVex Group, Inc., a privately held, venture-funded, biotechnology company headquartered in Woburn, Mass. BioVex is developing OncoVEX(GM-CSF), a novel oncolytic vaccine in Phase 3 clinical development, that may represent a new approach to treating melanoma and head and neck cancer.
Under terms of the agreement, Amgen will pay up to $1 billion: $425 million in cash at closing and up to $575 million in additional payments upon the achievement of certain regulatory and sales milestones. The transaction has been approved by the boards of directors of each company. It is subject to customary closing conditions, including regulatory approvals, and is expected to close in the first quarter of 2011. Following the completion of the transaction, BioVex will become a wholly owned subsidiary of Amgen.
"OncoVex has demonstrated encouraging anti-tumor activity in clinical studies for the treatment of melanoma and head and neck cancer, and BioVex is currently enrolling patients into pivotal Phase 3 trials in both indications," said Roger M. Perlmutter, M.D., Ph.D., Amgen's executive vice president, Research and Development. "Amgen is particularly excited about joining with BioVex and its talented staff to focus on advancing this late-stage investigational therapy, with the hope of bringing it to market within the next few years."
"Amgen is ideally positioned to leverage the potential of OncoVEX in multiple solid tumor indications given their impressive oncology franchise and expertise in biologics manufacturing and development," said Philip Astley-Sparke, chief executive officer of BioVex. "We have a shared vision and commitment to bring novel therapeutics to market and we are looking forward to being able to combine our efforts towards this common goal."
Amgen will discuss the transaction on a conference call today with the investment community at 2:00 p.m. Pacific Time. The previously-scheduled conference call will also discuss Amgen's fourth quarter and full year financial results. Live audio of the conference call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public. The conference call, including the question and answer session, is expected to last approximately one hour.
The webcast of the conference, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 72 hours after the event.
About Amgen
Amgen discovers, develops, manufactures, and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and vital medicines, visit www.amgen.com.
About BioVex
BioVex is a privately held biotechnology company based in Woburn, Mass. where it also has an operational commercial scale manufacturing facility. The Company is developing a new class of potent biologics for the treatment of cancer and prevention of infectious disease. In addition to OncoVEX(GM-CSF), the Company has a second development program, ImmunoVEX(HSV2) a vaccine for genital herpes that is undergoing clinical testing in the United Kingdom.
About OncoVEX(GM-CSF)
OncoVEX(GM-CSF) is a novel therapeutic cancer vaccine with both oncolytic and immunomodulatory activities. BioVex believes OncoVEX(GM-CSF) has the potential to offer a breakthrough option in the treatment of many solid tumors based on the strength of clinical data so far generated coupled with the relatively benign side effect profile noted to date. Previous clinical trials have enrolled patients with breast cancer, melanoma, head and neck cancer and pancreatic cancer, with indications of clinical activity being observed in each. BioVex is currently conducting a Phase 3 study in metastatic melanoma (the OPTiM study) following the proportion of durable complete remissions in a Phase 2 study using OncoVEX(GM-CSF) as a stand-alone therapy. A second Phase 3 study in Head & Neck cancer commenced in December 2010. For further information, please go to www.biovex.com.
NCI Sponsors Randomized Phase II Pancreatic Cancer Trial
Great news to see another Randomized Phase II trial sponsored by the NCI/NIH. The ONCY clinical program has broadened out to inlcude 6-7 major cancer indications; SCC Head and Neck, Melanoma, NSCLC, Pancreatic, Ovarian as well as Sarcomas and SCC Lung...as well as childhood cancers
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-prnews-3939218916.html?x=0&.v=20
Press Release Source: Oncolytics Biotech Inc. On Tuesday January 18, 2011, 7:30 am EST
CALGARY, Jan. 18 /PRNewswire-FirstCall/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC.to - News) announced today that the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, has agreed to sponsor a 2-Arm randomized Phase II study of carboplatin, paclitaxel plus REOLYSIN® versus carboplatin and paclitaxel alone in the first line treatment of patients with recurrent or metastatic pancreatic cancer. The NCI is sponsoring the trial under its Clinical Trials Agreement with Oncolytics, while Oncolytics will provide clinical supplies of REOLYSIN. The Principal Investigator is Dr. Tanios Bekaii-Saab of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
"Pancreatic cancer is typically diagnosed at a later stage, when there is a poor prognosis for long-term survival," said Dr. Tanios Bekaii-Saab, principal investigator. "Although the standard of care has evolved over the last few years, it has only managed to generate very modest improvements in response rate and median overall survival. Given these poor outcomes, we are eager to evaluate new and promising treatments in this indication."
The study is an open-label, multi-institution, 2-arm Phase II randomized study of patients with metastatic pancreatic cancer.
Patients will be randomized to receive either carboplatin, paclitaxel plus REOLYSIN (Arm A) or carboplatin and paclitaxel alone (Arm B). Patients in both arms will receive treatment every three weeks (21-day cycles). Patients in both arms will be receiving standard intravenous doses of paclitaxel and carboplatin on day one only. In Arm A, patients will also receive intravenous REOLYSIN at a dose of 3x1010 TCID50 on days one through five. Tumor response assessment will be done by CT scan and conducted every eight weeks. Patients that progress on carboplatin and paclitaxel (Arm B) will have REOLYSIN added. If patients experience significant toxicity related to carboplatin and/or paclitaxel they may continue with single agent REOLYSIN.
The primary objective of the trial is to assess improvement in progression-free survival with REOLYSIN, carboplatin and paclitaxel relative to carboplatin and paclitaxel alone in patients with metastatic pancreatic cancer. The primary endpoint is progression free survival in both arms. Secondary endpoints include overall response rate and overall survival. The study is expected to enroll approximately 70 patients.
"We continue to expand our clinical relationship with the NCI, as they push forward innovative research initiatives," said Dr. Brad Thompson, President and CEO of Oncolytics. "Partnering with the NCI allows us to cost-effectively expand the evaluation of REOLYSIN into new indications, with a focus on identifying additional targets for future late-stage clinical testing."
This is the fourth clinical trial using REOLYSIN to be sponsored by the NCI. The NCI is currently conducting a Phase II metastatic melanoma trial, a Phase I/II ovarian, peritoneal and fallopian tube cancer trial, and has announced its intention to sponsor a randomized Phase II trial in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer.
About Pancreatic Cancer
The American Cancer Society estimates that 43,140 Americans were diagnosed with pancreatic cancer and an estimated 36,800 Americans were expected to die from the disease in 2010. The prognosis for patients diagnosed with pancreatic cancer, regardless of stage, is generally poor; the relative five-year survival rate for all stages combined is approximately 6%.
About the NCI
The U.S. National Cancer Institute (NCI) is part of the National Institutes of Health and the U.S. Department of Health and Human Services. NCI's main responsibilities include coordinating the National Cancer Program; conducting and supporting cancer-related research; training physicians and scientists; and disseminating state-of-the-art information about cancer detection, diagnosis, treatment, prevention, control, palliative care, and survivorship.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
NCI Journal highlights clinical progress of Oncolytic Viruses
Oncolytic Viruses Move Forward in Clinical Trials
by Karen Rowan
A specially engineered strain of measles virus produced promising, albeit preliminary, results in patients with recurrent ovarian cancer in a phase I trial reported by researchers at the Mayo Clinic in Rochester, Minn. The measles virus, one of few oncolytic viruses currently in clinical trials, putatively works by selectively entering cancer cells, altering their gene expression, and causing them to fuse with neighboring cells, which leads to apoptosis.
In the trial, physicians treated 21 patients via intraperitoneal administration with a measles virus altered to express carcinoembryonic antigen, a marker protein that can allow real-time monitoring of viral gene expression. The median survival of the patients was 12.15 months, which appeared to be about double the expectation based on historical control subjects, according to the Mayo researchers, writing in the February Cancer Research. They observed no dose-limiting toxic effects.
Researchers hope that the first oncolytic virus cancer treatment could be approved in the U.S. in the next few years. Ever since safety trials allayed initial apprehensions about using viruses, researchers have been seeking a viral treatment that offers both selectivity for cancer cells and potency in killing them. The oncolytic virus farthest along so far is a modified herpesvirus now being tested in a phase III trial for patients with stage III or IV melanoma. Two other viruses are in phase II trials (see sidebar), and others, such as the measles virus, are in preclinical and early clinical studies.
Drug name (company) Phase Cancer(s)
OncoVEX GM-CSF (BioVex)
III Metastatic melanoma
III Head and neck cancer (accrual to start by end of 2010)
JX-594 (Jennerex)
II Hepatocellular carcinoma
II Hepatocellular carcinoma (with sorafenib)
II Metastatic colorectal cancer (accrual to begin summer 2010)
Reolysin (Oncolytics Biotech)
III Head and neck cancer(with carboplatin and paclitaxel; accrual to begin spring 2010)
I/II Ovarian, peritoneal or fallopian tube carcinoma
I/II Malignant gliomas
(UK trial) Metastatic colorectal cancer
(UK trial) Advanced malignancies
II Metastatic pancreatic adenocarcinoma (with gemcitabine)
II Non–small-cell lung cancer (with paclitaxel and carboplatin)
II Head and neck cancer (with paclitaxel and carboplatin)
II Metastatic melanoma
II Metastatic melanoma (with paclitaxel and carboplatin)
II Squamous cell carcinoma; lung
Oncolytic Virus Clinical Trials
Although not necessarily a complete list, the following are phase II and III trials either ongoing or planned.
Evanthia Galanis, M.D., who led the measles virus trial at the Mayo Clinic, said that in the 1970s case reports emerged of children with lymphoma in developing countries who got measles and whose cancer disappeared over the natural course of their measles infection. These reports prompted her interest, and she started working with vaccine strains of the virus in 2000.
The key to the virus's selectivity for cancer cells is that it enters cells through the CD46 receptor. Many tumors cells over express this receptor, which protects them from destruction by the immune system's complement proteins. Crucial to the virus's effectiveness, Galanis said, is that it causes an infected cell to fuse with its neighbors, killing 50–100 cells at a time.
Early work on oncolytic viruses suffered from a dearth of data showing their effectiveness. “In the early years, we made them so safe that they were not effective,” said John Bell, Ph.D., senior scientist at the Ottawa Hospital Health Research Institute and professor at the University of Ottawa. Bell is also chief scientific officer of Jennerex, one of the few companies working on oncolytic viruses.
Among the first viruses to be tested in the clinic was an adenovirus, engineered with a gene deletion that made it selectively infect p53-deficient cells and known as ONYX-015. A phase I study published in 2002 showed that the treatment was safe but found no antitumor effect.
In the Clinic
The field has evolved, Bell said, and researchers have come to understand that the viruses must be potent enough to spread within the body to be effective. The three oncolytic viruses that are in or close to phase III trials, he said, have this increased potency.
The phase III herpesvirus trial is now about midway through its accrual of 360 patients with melanoma, and complete accrual is expected by the end of 2010, said Robert Coffin, Ph.D., chief technology officer of BioVex, the Woburn, Mass., company that produces the agent. In addition to two gene deletions that render it unable to replicate in healthy cells, the virus has been engineered to contain the gene for granulocyte–macrophage colony-stimulating factor (GM-CSF), which may boost its effectiveness.
The treatment, called OncoVEX GM-CSF, is given by intratumoral injection, which some argue will limit its usefulness in treating systemic disease. But the infected tumor cells’ production of GM-CSF, said Coffin, heightens the immune response when the tumor cells disintegrate and essentially creates a vaccine against the cancer cells within the patient's body. Coffin pointed to the results of the phase II study, published in the Journal of Clinical Oncology in December, in which 10 of 50 patients experienced a complete response, and five a partial response, as evidence of the virus's potency. The virus has also been approved for testing in another phase III trial in head and neck cancer, which Coffin said should start later this year.
A second oncolytic virus that Bell said is near phase III is a vaccinia poxvirus also engineered to contain GM-CSF. The virus is selective for cancer cells because, to replicate, it requires an activated EGFR-ras pathway, and this pathway is constitutively activated in many cancers. The agent is known as JX-594 and is currently in two phase II trials for metastatic liver cancer (in one trial JX-594 is being given as a single agent; in the other, in combination with sorafenib). The virus has also shown an ability to infect tumor vasculature, so it may be harder for the tumor cells to develop resistance, said Bell. In the phase I study with this virus, published in Lancet Oncology in 2008, researchers found it in noninjected tumors, a sign that it may work on systemic disease.
The third virus is a modified reovirus, a common virus that can infect the human respiratory system or gastrointestinal tract, which is now being tested in 10 clinical trials. Miguel A. Villalona, M.D., director of medical oncology at Ohio State University Comprehensive Cancer Center in Columbus, is working on a phase II trial to test the virus (Reolysin, Oncolytics Biotech) in patients with metastatic non small-cell lung carcinoma.
The virus putatively replicates only in cells with an activated KRAS protein, Villalona said, and because Kras is commonly activated in many types of cancers, the virus may be used to treat different types of cancers.
Much of the general population has been exposed to reovirus, Villalona said, so the challenge may be to overcome the immunity that patients already have against it. Villalona's trial is giving the virus along with drugs (carboplatin and paclitaxel) in an attempt to lower the immune response and increase the viral dose in the tumor.
Previous Section
The Challenge: Monitoring Replication
A challenge in many virotherapy trials, said Mayo Clinic's Galanis, is monitoring the replication of the virus. Her work added the gene for carcinoembryonic antigen (CEA) to the measles virus as a marker of viral gene expression. As the virus replicated, CEA was produced within the intraperitoneal cavity, and the investigators assayed CEA levels in the fluid and in the blood to assess the level of viral gene expression. The elevation of CEA levels was dose dependent, but the effect was detectable in only three of the patients.
The ability to detect viral replication levels without resorting to tissue biopsy specimens is valuable, said Galanis, because it allows physicians to base treatment on the actual level of virus within the target cells.
“In an ideal world, we would like to be able to assess viral gene expression and replication noninvasively. If the virus has not replicated enough, we could increase the dose. If there was uncontrolled replication, we could be prepared to protect the patient. If we saw the replication levels drop after initial increase, this could determine optimal timing for another viral dose.” Such monitoring would allow physicians to individualize treatment for their patients, she said.
Galanis is now conducting another phase I trial in ovarian cancer patients by using a different marker: the sodium iodine symporter gene. She would like to optimize the ability to monitor viral replication, along with making other improvements to the treatment's efficacy, before moving on to a phase II trial, she said.
“This is a huge growth area,” Bell said. “We need to be able to measure the viral replication.” This is different from other therapies, he said, because the virus grows inside the tumor, so its levels are not uniform throughout the body. “The rest of us need to follow on with this idea.”
“The work done at the Mayo Clinic with real-time monitoring was interesting and clever,” said Coffin, but whether the ability to measure viral replication will lead to real improvements in efficacy or measurable benefits to patients remains to be seen.
If phase III trials are successful, Bell said, the next step will be to scale up production of the agents, “and we don’t yet know what the issues with that will be.”
© Oxford University Press 2010.
Enrollment Opens in US Phase I Colorectal Cancer Study
The second follow on part of this trial has been announced to be a randomized Phase II. It should be noted that this trial is for KRAS positive screened test subjects
Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) announced today that a U.S. Phase I study of REOLYSIN® in combination with FOLFIRI (Folinic Acid (leucovorin) + Fluorouracil (5-FU) + Irinotecan) in patients with oxaliplatin refractory/intolerant Kras mutant colorectal cancer (REO 022) is now open to enrollment. The principal investigator is Dr. Sanjay Goel of the Montefiore Medical Center at The Albert Einstein College of Medicine in New York.
"We continue to advance REOLYSIN into clinical testing in new indications where we believe the product may have sound clinical and commercial potential," said Dr. Brad Thompson, President and CEO of Oncolytics. "We are focusing our clinical program increasingly to look at patients with Kras mutant cancers by either pre-screening patients for Kras status, as in the case of this study and the Phase II trial we are running in non-small cell lung cancer (REO 016), or by selecting indications with widespread Kras involvement, such as our ongoing Phase II study in advanced pancreatic cancer (REO 017)."
The trial is a Phase I dose escalation study with three dose levels, comprising cohorts of three to six patients, to determine a maximum tolerated dose and dose-limiting toxicities with the combination of REOLYSIN and FOLFIRI. FOLFIRI will be administered on the first day of a two week (14-day) cycle, while REOLYSIN will be administered on days one through five of a four week (28-day) cycle.
Eligible patients include those with histologically confirmed cancer of the colon or rectum with Kras mutation and measurable disease. They must have progressed on or within 190 days after last dose of oxaliplatin regimen as front-line therapy in the metastatic setting or be intolerant to oxaliplatin. The study is expected to enroll 12 to 20 patients.
The rationale for conducting the study is based on signals of efficacy seen in a range of preclinical and clinical work with REOLYSIN. This includes a National Cancer Institute screen of seven colorectal cancer cell lines (four with ras mutations), all of which were susceptible to REOLYSIN; preclinical research into the efficacy of REOLYSIN in combination with various chemotherapeutic agents in colorectal cancer cell lines; observation of CEA responses and stable disease in colorectal patients in a phase I study of REOLYSIN as a monotherapy; and interim results from a translational study with REOLYSIN as a monotherapy that is currently ongoing, which showed evidence of viral replication and tumour cell death in four of six patients with metastatic colorectal cancer analyzed to date, two of which had confirmed Kras mutations in codon 12.
About Colorectal Cancer The American Cancer Society estimates that nearly 143,000 Americans were diagnosed with colorectal cancer and an estimated 51,370 died from the disease in 2010. The prognosis for patients diagnosed with colorectal cancer at the localized stage is good with a five-year survival rate of 91%, however only about 39% of cases are diagnosed at this stage; five-year survival rates drop to 70% with the spread to adjacent organs or lymph nodes and 11% for distant metastases. Colorectal cancer is the third leading cause of cancer death among both men and women in the United States.
About Oncolytics Biotech Inc. Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. REOLYSIN preferentially replicates in cancer cells that have an activated RAS pathway. Approximately two thirds of all cancers have an activated RAS pathway, including most metastatic disease. A large number of mutations, including mutations in EGFR, Her2 or Kras along the RAS pathway lead to RAS pathway activation. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
RBC Increases Target to $7.00
Partnering Should be Assisted by Newsflow and Bought Deal
Valuation: Increasing Target to $7.00 from $5.00.
Bought Deal Raises $28.8M. The company completed a bought deal priced at $4.60 per unit. Initially 5.44M units were sold and combined with the 0.82M over allotment units, the company raised $28.8M in gross proceeds. Funds will be used to finance the phIII H&N cancer trial and additional projects.
Next 12 Months to Remain Important. We continue to believe 2010 and early 2011 will likely be transformational as ONC has multiple potential catalysts occurring over the next 12 months that may impact investor sentiment. These include:
• Data release from ONC's NSCLC phII trial in Q1/11
• Data by Q1 from the phII metastatic melanoma trial.
• Interim Phase III pivotal trial data in H&N cancer in H1 2011.
• A potential partnership deal by mid 2011.
Model Revisions: We have made minor changes to our model following the release of the Q3 results and financing. Our updated 2010 and 2011 EPS estimates are ($0.26) and ($0.17), respectively, vs. ($0.31) and ($0.20) previously.
Outlook: Outlook Improves as Bought Deal and Data Releases Should Assist with Partnering Negotiations. There were no surprises in Q3 and more importantly the trials appear to be progressing largely as expected. As a reminder, ONC directly supports 4 of the 11 ongoing trials while other (NCI, CTRC, Leeds) sponsors are funding the remaining trials. The additional sponsors reduce the investment risk and increase Reolysin penetration into other cancer indications.
The recent bought deal also allows ONC to comfortably advance the phIII H&N cancer trial and other early stage projects. With less pressure on the balance sheet and news from multiple trials forthcoming, Oncolytics should be able to extract additional value from potential partners as negotiations move forward. As a result, our outlook has improved as data from multiple trials and signing of a partnership deal should serve as catalysts for the stock in 2011.
Outperform
ONCY has a few more followers than you may think
Count me in that camp. Nice 27% move this week and the last month has been pretty good.
BioStockResearch covers ONCY as one of the few select companies in their model Biotech portfolio and newsletter but I wont speak for David.
Granted there are lots of questions that past trials may not have answered to those who require proof from randomized trials but the extensive open label Phase 1 and broad Phase II path ONCY has chosen has positioned it to report up to 4 Phase II trials (NSCLC RAS+, Melanoma, H&N, and maybe Pancreatic)and hopefully a look at the first look point (70 patients) of the randomized Phase III H&N at ASCO next June.
Recent new trials that have started in the last month have been randomized with the NCI paying the bill and patient advocacy groups running the trials. (Ovarian and Pediatric tumors)
There are a lot of vocal parties that criticize the company and its management and some of it is justified however when you are working with a live replication competent virus you are dealing with unchartered science and a little slack is warranted.
In the end viral therapy may or may not work but at this point I see enough evidence of a MOA from trials that demonstrated viral replication in tumours and resolution of distant metastatic liver and colon tumors after treatment with Reolysin to warrant my investment. Should even one indication pan out for this virus, it will be big news.
You can also look to Biovex in MA that is private and working on another viral based treatment that seems to be having similar preliminary results and is running two Phase IIIs right now.
ONCY had a low of $1.00 about 2 years ago and the move to $6.38 Friday shows that there is very strong interest in this stock all of a sudden. These are open label trials running, and if a partnership were going to happen it will most likely be in the next 6 months and from my perspective the time is now to partner because with good results in several trials the need to broaden the clinical program is now.
For those of you open to looking at ONCY, you can do some DD at the ONCY iHub board at:
http://investorshub.advfn.com/boards/board.aspx?board_id=814
My latest post talks about the 37% increase in Institutional ownership in the last 3 months .... MNTA was also mentioned in the same article.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=57594392
cheers
onco_investor
Institutional Interest Increases 37+% Last 3 Months
8 Drug-Related Stocks Being Chased by the Smart Money
http://www.fool.com/investing/general/2010/12/07/8-drug-related-stocks-being-chased-by-the-smart-mo.aspx
By Eben Esterhuizen and Alicia Sellitti, Kapitall | More Articles
December 7, 2010
Moody's, Wall Street's preeminent credit rating agency, recently released its forecast for the pharmaceutical industry. Unfortunately, the outlook for the next couple of years isn't terribly encouraging. With a host of major patent expirations on the horizon for 2011 and 2012 (including household names like Lipitor and Zyprexa), expect to see a slew of cheap generics flood the market -- and the effect on profit margins could be epic.
Big pharma companies will need to be armed with a host of late-stage pipelines to offset the impact -- and by and large, development just isn't where it needs to be.
And the drugs in the home stretch of development will still have to contend with administrative obstacles, of which there are many. Just look at how difficult the FDA makes it for new products to hit the U.S. marketplace -- and we're not the only country with fussy regulators.
What's more, with Europe's debt crisis wreaking havoc on the global economy, look for increasingly severe austerity measures in health care -- and drug spending is likely to be a prime target.
Moody's expects to see a good deal of debt-financed consolidation in the industry -- meaning that companies will issue debt in order to buy up stock in other pharmaceutical companies. But according to Moody's analyst Marie Fischer-Sabatie, it's going to take more than that to neutralize the negatives.
In her estimation, it will be companies with "robust" pipelines and "diversified players," with enough heterogeneity to diffuse risk, that will emerge from lean times no worse for the wear.
So which stocks are worth investing in? It's tough to say right now, but institutional investors' trades may offer up some clues. (Click here to access free, interactive tools to analyze these ideas.)
Here's a list of eight biotech or pharma stocks being chased by the smart money.
Company
Shares Held by Inst. Investors Today
Shares Held by Inst. Investors 3 Months Ago
% Change in Inst. Ownership
AVEO Pharmaceuticals (Nasdaq: AVEO)
26,299,655
17,349,740
51.59%
Amarin (Nasdaq: AMRN)
47,667,378
32,616,772
46.14%
Oncolytics Biotech (Nasdaq: ONCY)
1,660,104
1,204,450
37.83%
Avanir Pharmaceuticals (Nasdaq: AVNR)
58,618,069
46,113,392
27.12%
Crucell (Nasdaq: CRXL)
10,585,511
8,343,376
26.87%
Protalix BioTherapeutics (NYSE: PLX)
16,023,243
12,706,530
26.10%
Momenta Pharmaceuticals (Nasdaq: MNTA)
40,183,667
32,706,478
22.86%
Halozyme Therapeutics (Nasdaq: HALO)
47,896,172
39,878,772
20.10%
Institutional data sourced from Reuters. The list has been sorted by change in institutional ownership over the past three months.
Here is the current weekly chart from the last 2+ years or so.
and the current daily chart from the last 6 months where you can see the volume jump
Nice looking charts.
FDA OKs Conmed Tissue Device
http://finance.yahoo.com/news/FDA-OKs-Conmed-Tissue-zacks-2975200425.html?x=0&.v=1
Surgical devices maker Conmed Corp (NasdaqGS: CNMD - News) has secured approval from the U.S. Food and Drug Administration (FDA) for its new tissue sealing device for use in a broad range of surgeries. The device, dubbed Altrus Thermal Tissue Fusion System, uses thermal energy to seal, cut, grasp and dissect vessels up to 7 millimeter (mm) in size.
The market for energy-based instruments is worth roughly $1.5 billion and is reportedly growing 11% annually. The use of these devices has expanded in surgical settings over the last few years to reduce procedure time and cost and improve patient outcome.
Conmed expects Altrus to generate modest revenues of between $5 million and $10 million in 2011. While the device is not expected to deliver meaningful profit initially (given the start-up costs), the company reckons it as a long-term growth driver. Conmed expects Altrus to make significant penetration of the tissue sealing market and emerge as a better alternative to the existing products available for surgeons.
Conmed is a major medical products manufacturer specializing in surgical instruments and devices. The company is poised to benefit from the uptrend in the adoption of minimally invasive techniques as a large percentage of its products are designed for these procedures, representing an attractive opportunity to sustain revenue growth.
Conmed derives roughly 75% of its total revenues from single-use disposable products, which remain the mainstay of its business. Hospitals and clinics are expanding the use of these products, which reduce overheads from sterilizing surgical instruments and products following surgery.
However, Conmed operates in a highly-competitive orthopedic surgery market against much larger, more technically-competent companies, such as Johnson & Johnson (NYSE: JNJ - News), Smith & Nephew (NYSE: SNN - News) and Stryker Corporation (NYSE: SYK - News).
Moreover, the orthopedic industry faces severe pricing pressure and Conmed is no exception. Conmed is also susceptible to foreign exchange headwinds, which may drag its top line moving forward. We currently have an Underperform recommendation on Conmed.
Oncolytic Viruses: The Future of Cancer Therapy?
http://biomedreports.com/2010112260394/oncolytic-viruses-are-they-the-future-of-cancer-therapy.html
Written by Douglas W. Loe, PhD, MBA
Monday, 22 November 2010 01:42
Chemotherapy—as any cancer patient will tell you—is not for the faint of heart, but it can kill many forms of cancer. Some form of chemotherapy, originally discovered as a cancer treatment almost 70 years ago, is still routinely prescribed for most types of the disease. The treatment works by targeting fast-growing cells, like those typically found in rapidly growing tumors. But while chemotherapy can shrink tumors, they often grow back and become resistant, or refractory to the treatment.
To combat this resistance, chemotherapy is now often used in combination with other treatments that have different mechanisms for attacking and killing cancer cells. Doctors must be cautious when combining treatments to ensure that the regimen does not become too toxic for patients to tolerate. The goal is to introduce drugs that can be used synergistically with chemotherapy to not only extend life, but to improve quality of life while undergoing treatment.
The Potential of Oncolytic Viruses
One approach that has proven quite promising is known as oncolytic virotherapeutics. Here, viruses are harnessed to infect, multiply within and subsequently lyse cancer cells; the virus targets tumors without affecting normal tissue.
Several types of oncolytic viruses have been developed to date. These include the adenovirus, which is a non-enveloped virus with a double-stranded, linear DNA genome that forms particles that are 70 to 90 nm in size. There are multiple engineered versions of this virus in clinical trials, including Onyx-015 and H101. The latter has been approved in China and is sold by Shanghai Sunway Biotech.
A second form of oncolytic virus is Newcastle-disease virus (NDV). This is an enveloped virus with a single-stranded, negative-sense RNA genome that forms pleiomorphic particles ranging from 150 to 300 nm. Naturally attenuated versions, such as PV701, are in clinical development. Although still in Phase I testing, slow virus infusion rather than injection seems to mitigate side effects. The Maryland-based private firm Wellstate Biologics has two Phase I open-label PV701 cancer trials ongoing.
Poxviruses are a family of enveloped viruses that contain a double-stranded, linear DNA genome and form particles that are 200 nm in diameter and 300 nm in length. Myxoma and vaccinia are family members that are under therapeutic development. Among several candidates, the most advanced is probably Jennerex’s JX-594, which is entering a Phase II liver cancer trial in partnership with Transgene (see below) and which could enter a Phase II colorectal cancer study imminently, testing JX-594 in patients refractory to Eli Lilly’s (NYSE: LLY ) leading EGFr-targeted antibody drug Erbitux. Interim data are already available from nine patients in a small Phase I/II liver cancer study showing disease stabilization in at least five patients when JX-594 is administered with Bayer’s approved liver cancer drug sorafenib (branded as Nexavar). JX-594 performed just as well in a separate Phase I liver cancer study where it was tested as monotherapy and not in combination with Nexavar. Interim data from 24 patients in that trial showed disease stabilization at two months in most JX-594-treated patients, providing solid evidence of JX-594 oncolytic virus potency at treating this cancer form.
Oncolytic Viruses: An Approved Product on the Horizon?
Oncolytic Viruses in Cancer Therapy
It may come as a surprise to some that the herpes simplex virus is also under consideration as an oncolytic virus. This is an enveloped virus with a double-stranded, linear DNA genome that forms particles that are 150 to 200 nm. Many engineered versions are in clinical trials for the treatment of patients with cancer, such as OncoVEXGM-CSF, G207, HSV-1716 and NV1020. The most advanced of these is OncoVEXGM-CSF, a combination of the oncolytic virus OncoVEX plus granulocyte macrophage-colony stimulating factor (GM-CSF) developed by Massachusetts-based private firm BioVex; the combination is already well-advanced in a 360-patient Phase III advanced melanoma trial and a 528-patient Phase III head & neck cancer trial design has been endorsed by the U.S. FDA under a Special Protocol Assessment and could begin later this year, or perhaps early 2011. G207 was developed by the German firm Medigene, which recently completed a Phase II brain cancer trial, and was also developing NV1020, which recently completed testing in a 27-patient Phase II liver metastasis from colon cancer trial. However, neither oncolytic virus formulation is identified in Medigene’s clinical pipeline at present. UK-based Crusade Laboratories tested HSV-1716 in a Phase I oral cancer trial; a Phase III GBM trial is being planned as are Phase I/II ovarian cancer and liver cancer trials. And lastly, BioSante Pharmaceuticals’ (Nasdaq:BPAX) adenovirus CG0070 was recently sold to private biotech firm Cold Genesys; the virus performed well in a 35-patient Phase I bladder cancer trial conducted by innovator Cell Genesys, and based on those data, the virus could advance into Phase I/II bladder cancer testing at company discretion.
Picornaviruses are a family of non-enveloped viruses with single-stranded, positive-sense RNA genomes that form particles that range from 18 to 30 nm. Members of this family that are being tested as oncolytic therapeutics include coxsackieviruses and engineered versions of poliovirus. The latter is in development at a few locations, including research institutes at Duke University and Stony Brook University, and has shown some preclinical efficacy against GBM and neuroblastoma. The firm Viralytics is developing the coxsackievirus A21 in a Phase I advanced melanoma study.
Vesicular stomatitis virus (VSV) is an enveloped virus with a single-stranded, negative-sense RNA that forms 65 to 185 nm bullet-shaped particles. This virus is still in the research stage; two constructs have recently been tested at the Mt. Sinai School of Medicine in New York.
Reoviruses: The Most Promising Option?
Finally, we come to what some consider the most promising form of oncolytic virus: the reovirus. This is a non-enveloped virus with a double-stranded, segmented RNA genome that forms particles that are 60 to 90 nm. The reovirus preferentially replicates in cancer cells that feature a common mutation known as an “activated Ras pathway,” while sparing normal cells. This makes it intrinsically tumor selective without the need for any genetic manipulation.
Reovirus is a virus with no known associated disease. It replicates in the cytoplasm and therefore does not integrate into the cell’s DNA. Reovirus is found everywhere in nature and has been isolated from untreated sewage, river and stagnant waters. Exposure to reovirus is common in humans, with half of all children by the age of 12 having been exposed and up to 100% testing positive by adulthood.
Tumors bearing an activated Ras pathway cannot activate the anti-viral response mediated by the host cellular protein, PKR. Studies have shown that reovirus actively replicates in transformed cell lines with an active Ras signaling pathway, eventually killing the host cell and freeing the viral progeny that go on to infect and kill more Ras-activated tumor cells. When normal cells are infected with reovirus, the immune system can neutralize the virus. Approximately one-third of human cancers have activating mutations in the Ras gene itself, and it is possible that more than two-thirds of cancer cells have an activated Ras signaling pathway because of activating mutations in genes upstream or downstream of Ras.
How Reoviruses Might Help
While it has been demonstrated in animal studies that reovirus is capable of treating metastatic cancer in immunocompetent mice, it has also been shown that reovirus used in conjunction with immunosuppressive drugs can effectively prolong animal survival. Combining IV reovirus therapy with Cyclosporine A, an immune suppressant, significantly inhibited tumor regrowth. In a model of disseminated LLC metastatic lung cancer in C57BL mice, treatment with reovirus and either Cyclosporine A or T cell depleting antibodies (anti-CD4 and anti-CD8 Ab) led to an increase in survival compared to treatment with reovirus alone.
The above results supported the development of clinical protocols in which immune suppressive drugs could be combined with a systemically administered reovirus in the treatment of cancer. The combination of reovirus with various chemotherapies in human colorectal cancer cell lines demonstrated synergistic cytotoxic activity. In addition to modulating the immune response, the use of chemotherapies along with reovirus treatment may enhance intratumoral spread of the virus.
Calgary-based Oncolytics Biotech, Inc.(Nasdaq:ONCY) has developed a biologic agent, Reolysin, from naturallyoccurring reovirus. The virus has demonstrated impressive results in clinical trials on its own, but particularly in combination with certain chemotherapeutics. In preclinical studies in a wide variety of cancer cell lines, investigators found that when used together, reovirus and chemotherapy resulted in more efficient and synergistic anti-cancer activity than when each agent was used on its own.
These combinations are showing extremely good results in human trials, particularly in refractory head and neck cancer patients. Many head and neck cancer patients treated with a combination of Reolysin and chemotherapy to date have experienced dramatic and prolonged tumor shrinkage, without increasing adverse side effects. A pivotal 180-to-480-patient Phase III head and neck cancer study commenced this year and could generate survival data in a few years. Non-small cell lung cancer (NSCLC) is another potential target for this treatment combination. The Cancer Therapy & Research Center at the University of Texas Health Science Center—a big proponent of oncolytic viruses—has committed to funding up to five Phase II clinical trials using Reolysin in combination with chemotherapy against a variety of advanced cancers. And based on solid evidence that Reolysin could be effective as an anticancer agent targeting tumor types with activated Ras pathway, Oncolytics Biotech and clinical collaborators are actively testing Reolysin in ovarian cancer, colorectal cancer (though only in patients harboring mutated Kras gene), melanoma, sarcoma, and pancreatic cancer, for which tumor response data could be available in a year or two.
It is difficult to provide a crystal-clear economic forecast for oncolytic viruses as a whole, but an indicator of their potential future sales earnings can be derived from examining four recently-launched anticancer therapies already on the market. One of these is erlotinib, branded as Tarceva, developed by OSI Pharmaceuticals and launched in 2004 by Roche/Genentech and OSI. An oral small molecule tyrosine kinase inhibitor drug that is prescribed for patients with advanced-stage non-small cell lung cancer, it earned $20 million in 2004, $387 million in 2005, and $813 million in 2006. Sales reached $1.2 billion in 2009. Another is the immunomodulatory and anti-angiogenic drug thalidomide (branded as Thalomid), developed by Celgene and launched in 2003 for treating multiple myeloma, which enjoyed sales of $224 million that first year and reached $505 million by 2008. A third is lenalidomide (branded as Revlimid and also developed by Celgene), a drug structurally related to Thalomid that generated even more robust sales growth after its launch in 2006, achieving blockbuster sales in 2008 of $1.3 billion that grew to $1.7 billion last year. And a fourth is the oral alkylating agent temozolamide, branded as Temodar by Schering-Plough (now part of Merck) and approved as a glioblastoma (brain cancer) drug; Temodar generated $180 million in sales in 2001 that grew to $703 million in 2006 (its first full-year of sales in the U.S.) and exceeded US$1 billion in 2009. Though survival benefit of 11 weeks is modest, the drug (along with Roche’s Avastin) is still standard-of-care for patients with advanced brain cancer.
Partners and capital markets are now recognizing value in oncolytic viruses
The year-over-year, steadily increasing demand for the four drugs described above provides supporting evidence that demand for new and effective agents in oncology remains strong, giving us confidence that Reolysin could be similarly embraced if it performs well in Phase III testing. We are optimistic that global oncology-focused pharmaceutical firms will be keen to partner with Oncolytics once Reolysin Phase III head and neck cancer data are available, if not before, and capital markets are exhibiting optimism in Reolysin’s medical prospects through the company’s share price strength this year and through well-subscribed equity offerings in 2009/10.
And in other commercial advances in oncolytic virus development, Jennerex’s JX-594 is now partnered with the French biotechnology firm Transgene in a $116 million alliance that could pay Jennerex a double-digit royalty on future JX-594 sales if the drug performs well in pivotal liver cancer or colorectal cancer trials, or in other cancer indications contemplated in the alliance. The Transgene alliance seems to be focused on European and Middle East marketing rights and thus provides an opportunity for U.S. or Japan-based firms to partner with Jennerex in those regions.
As we have seen above, there are a number of oncolytic viruses that have shown potential use in cancer treatment and demand for more effective agents is strong. Future research studies will give us an even clearer perspective on which, if any, of these viruses offer the most effective route toward a reliable and commercially viable complement to chemotherapy for oncologists and their patients.
About the Author
Douglas W. Loe, Ph.D, MBA, is a consistently topped ranked healthcare and biotechnology analyst. He has covered Canadian biotech since 2000, initially as part of the research team at Yorkton Securities (now Macquarie Capital Markets), and has been with Versant since Fall 2002 where he covers a broad spectrum of drug development, medical technology, and healthcare services firms. Doug holds a MBA from Queen’s University and a Ph.D in biochemistry from the University of Guelph, working in the area of cancer chemotherapy and multidrug resistance, followed by post-doctoral training at the Queen’s University Cancer Research Institute. During his scientific career, he published multiple abstracts, peer-reviewed manuscripts and reviews related to P-glycoprotein and MRP-mediated multidrug resistance. He can be reached at DLoe@versantpartners.com. Versant Partners is a member of the Canadian Investor Protection Fund (CIPF).
Douglas W. Loe, PhD, MBA authored and submitted this article solely for the purpose of providing key expert analysis and opinion. No compensation was exchanged by either party in consideration for the publication of this material.
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Read the full report: http://biomedreports.com/2010112260394/oncolytic-viruses-are-they-the-future-of-cancer-therapy.html#ixzz16ALeCzWW
Childrens Oncology Group/NCI sponsor Pediatric Sarcoma Phase 1
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-prnews-3700037276.html?x=0&.v=23
Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) announced today that the Children's Oncology Group (COG) intends to conduct a Phase I trial of REOLYSIN® in combination with cyclophosphamide in pediatric patients with relapsed or refractory solid tumors. The study will be conducted in collaboration with the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, under its Clinical Trials Agreement with Oncolytics. Oncolytics will provide clinical supplies of REOLYSIN for this study. The study chair will be Dr. E. Anders Kolb of the Nemours/Alfred I. duPont Hospital for Children.
The study is an open label, multicentre, dose escalation Phase I study of REOLYSIN in patients aged three to 21 years with relapsed or refractory solid tumors. Patients will receive intravenous REOLYSIN on days one through five of each 28-day treatment cycle. Some patients will also receive oral cyclophosphamide on days one through 21. Treatments repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
The primary objectives of the trial include estimating maximum tolerated dose, and defining and describing the toxicities of REOLYSIN and REOLYSIN plus oral cyclophosphamide in this patient population. Secondary objectives include defining antitumor activity of REOLYSIN within the confines of a Phase I study, evaluating the development of neutralizing antibodies to REOLYSIN following intravenous administration of REOLYSIN alone and in combination with cyclophosphamide, and assessing the biologic activity of REOLYSIN. After completion of study treatment, patients are to be followed up periodically for up to one year.
"This trial builds on a range of completed preclinical work and clinical studies in adult patients, including a U.K. Phase I clinical study examining the use of REOLYSIN in conjunction with cyclophosphamide and a U.S. Phase II clinical study in sarcoma using REOLYSIN as a monotherapy," said Dr. Brad Thompson, President and CEO of Oncolytics. "It is very important to investigate the use of an agent in adults prior to proceeding to use in pediatric patients. With the work in adults well advanced, we can now move ahead in younger patients."
Information on the study will be available at www.clinicaltrials.gov.
About the NCI The U.S. National Cancer Institute (NCI) is part of the National Institutes of Health and the U.S. Department of Health and Human Services. NCI's main responsibilities include coordinating the National Cancer Program; conducting and supporting cancer-related research; training physicians and scientists; and disseminating state-of-the-art information about cancer detection, diagnosis, treatment, prevention, control, palliative care, and survivorship.
About Oncolytics Biotech Inc. Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company's expectations related to the Phase 1 trial in pediatric patients with relapsed or refractory solid tumours sponsored by the COG in collaboration with the NCI, and the Company's belief as to the potential of REOLYSIN as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN as a cancer treatment, the tolerability of REOLYSIN® outside a controlled test, the success and timely completion of clinical studies and trials, the Company's ability to successfully commercialize REOLYSIN, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements, except as required by applicable laws.
SOURCE Oncolytics Biotech Inc.
CEO Brad Thompson An Old YouTube
Dr David Kirn on YouTube Oncolytic Virus Program
CEO Jennerex Biotherapeutics
DrPatrick Lee: Reovirus... Promotes Protective Antitumor Immunity
AACR Journal: Molecular Cancer Therapeutics published Oct 26th 2010
http://mct.aacrjournals.org/content/early/2010/10/22/1535-7163.MCT-10-0590.abstract
Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity
Shashi A. Gujar, Paola Marcato, Da Pan and Patrick W.K. Lee
+ Author Affiliations
Authors' Affiliation: Department of Pathology and Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Corresponding Author:
Patrick W.K. Lee, Department of Pathology and Microbiology and Immunology, Dalhousie University, Room 7-P, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5. Phone: 902-494-8048; Fax: 902-494-5125. E-mail: patrick.lee@dal.ca
Abstract
Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response–mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumor-specific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1a, IL-1ß, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1a, RANTES, TNF-a, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen–specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC- or T cell–based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy–initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy. Mol Cancer Ther; 9(11); OF1–10. ©2010 AACR.
Footnotes
Note: Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).
Received June 23, 2010.
Revision received August 30, 2010.
Accepted August 31, 2010.
Bought Deal Financing Announced - $25Mil Canadian
http://www.digitaljournal.com/pr/147500
Oncolytics raised $25 Mil Canadian yesterday in a Canada based bought deal. Issuing approx 5.4 Mil common shares priced at $4.60 Canadian. (Over allotment could be up to 6.256 Mil shares netting $28.75 Million Canadian) Additional warrants exercisable for up to two years from today could net up to approx $19.2 Mil (6.256/2 Mil Warrants x $6.15 Canadian) The threat of financing overhang is now lifted. Any substantial news will have less resistance now IMO. For discussion only
CALGARY, Oct. 28 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX:ONC, NASDAQ:ONCY) today announced that it has entered into an agreement with a syndicate of underwriters pursuant to which they have agreed to purchase, on a bought deal basis, 5,440,000 units (the "Units") of the Company at a price of Cdn$4.60 per Unit for gross proceeds to the Company of approximately Cdn$25 million (the "Offering"). The Offering will be conducted through a syndicate of underwriters led by Paradigm Capital Inc., and including RBC Capital Markets, Canaccord Genuity Corp., and Bloom Burton & Co. Inc. (collectively the "Underwriters"). In addition, the Corporation has agreed to grant to the Underwriters an option (the "Over-Allotment Option") to purchase up to an additional 15% of the number of Units sold under the Offering at a price of Cdn$4.60 per Unit, on the same terms and conditions as the Offering, exercisable at any time, in whole or in part, until the date that is 30 days following the closing of the Offering. In the event that the Over-Allotment Option is exercised in its entirety, the aggregate gross proceeds of the Offering to Oncolytics will be approximately Cdn$28.75 million. Each Unit will consist of one common share of Oncolytics and one-half of one common share purchase warrant (each whole common share purchase warrant, a "Warrant"). Each Warrant will entitle the holder to acquire one common share of Oncolytics at a price of Cdn$6.15 at any time prior to the date which is two years following completion of the Offering.
Read more: http://www.digitaljournal.com/pr/147500#ixzz13kk7Dfv3
Publication by Dr. Matt Coffey in Sciencedirect
The use of immunohistochemistry to determine oncolytic reovirus distribution and replication in-human tumors
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WN5-50W80VR-1&_user=1025668&_coverDate=08/27/2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050549&_version=1&_urlVersion=0&_userid=1025668&md5=ff0e5031447619a69e25517e6b79a822&searchtype=a
Abstract
An oncolytic virus is considered a targeted cancer therapy due to its ability to specifically target, replicate in and lyse cancer cells while leaving normal cells unharmed. Over the last few years several tumor selective oncolytic viruses have been developed. These include certain DNA viruses such as adenovirus that have been genetically manipulated to target specific cancer cells by exerting restrictions on the virus at the level of cell entry, viral gene transcription and viral protein translation. There are a variety of RNA viruses being studied as possible cancer therapies including reovirus. Reovirus is intrinsically oncolytic without the need for any genetic manipulation. The inherent oncolytic properties of this virus are derived from the fact that it specifically targets cells with an activated Ras pathway found in many cancer cells. REOLYSIN® is a proprietary formulation of human reovirus type 3 Dearing developed by Oncolytics Biotech Inc. and is the only therapeutic reovirus in clinical development. This review provides an overview of the development of REOLYSIN as a potential cancer therapeutic and the growing role of in situ based molecular pathology methods in providing clinical proof of concept and in guiding clinical development.
Article Outline
1. Reovirus and transformed cells
2. Pre-clinical studies
3. Immune system
4. Clinical trial studies and evidence of viral targeting
5. REOLYSIN in combination with standard of care
6. Viral specificity and replication within human tumors
7. Discussion
i. Acknowledgements
ii. References
The rest of the article is $35.95
Thanks RJC, Can you post the geneman blurb as well?
and if you can please Email me at oncoinvestor@yahoo.com
Seeking Alpha... Pancreatic Cancer Clinical Trials ONCY
http://seekingalpha.com/article/232174-amgen-celgene-and-novartis-in-the-fight-against-pancreatic-cancer
The ONCY Phase II in pancreatic cancer is expected to report results in the next few months.
Next month [November] marks Pancreatic Cancer Awareness Month. Visibility for the disease is already on the rise due to recent celebrity victims, including Apple’s Steve Jobs and Hollywood actor Patrick Swayze.
According to the American Cancer Society, pancreatic cancer is a devastating disease with the worst mortality rate and an overall 5-year survival rate lower than 5%. Although accounting for only 3% of all cancers, this disease is the fourth leading cause of death and represents 6% of all cancer related deaths in the United States.
The disease remains one of the most difficult to treat due to late initial diagnosis and extreme resistance to treatment. For example, about 50% of patients have locally advanced disease at the time of diagnosis, indicating that the cancer has grown beyond the confines of the pancreas to invade surrounding vital structures, and in 40% of patients the tumor has spread to distant sites, such as the liver and lungs [metastatic stage]. Case in point: Patrick Swayze was diagnosed with stage IV pancreatic cancer that had already spread to the liver in March 2008 and lost his battle with the disease in September 2009 at the age of 57.
The majority of pancreatic tumors [95%] are adenocarcinomas that mainly develop from exocrine cells in the tissues of the pancreas. They are characterized by an aggressive behavior with a fast progression rate that makes them highly metastatic. Neuroendocrine tumors [NET] of the pancreas [islet cell tumors] are much less common [1-2%] than exocrine pancreatic tumors and are considered less deadly. For example, Steve Jobs, co-founder and chief executive of Apple Inc. (AAPL), was diagnosed with this rare, slow-growing pancreatic tumor in 2004.
In terms of treatment, surgical removal of the tumor represents the best option for pancreatic cancer patients without invasion into surrounding organs or distant metastasis. Unfortunately, only 15–20% of all patients are candidates for potentially curative surgery. Depending on the tumor localization, pancreaticoduodenectomy, distal or total pancreatectomy can be performed. However, even with an optimal curative surgery, metastases often occur. Median survival time without evidence of recurrent disease is 21.2 months after resection.
For locally advanced or metastatic disease, treatment is still palliative rather than curative, and chemotherapy remains the only option. Since its approval in 1997, Eli Lilly’s (LLY) Gemzar® [gemcitabine] is the current standard first-line treatment in the U.S. It has been shown to improve the median time to disease progression and overall survival [OS].
Just like lupus, sepsis, and several others, pancreatic cancer has been referenced as one of those challenging diseases where good drugs [and companies…] go to die. Since 2005, nine late-stage clinical trials have been performed to improve the efficacy of gemcitabine with little success in terms of improving survival outcomes [see Table 1]. Such failures resulted in at least two companies filing for bankruptcy [both Aphton Corp and Therion Biologics in 2006]. In fact, the only combination approved by the U.S. Food and Drug Administration [FDA] is gemcitabine plus Astellas Pharma’s Tarceva® [erlotinib], which increased the median OS from 6.0 to 6.4 months.
Table 1. Prominent Late-stage Pancreatic Product Failures
Company Product Class
GenVec, Inc.(GNVC) for TNFerade-Gene therapy
Pfizer, Inc.(PFE) for Axitinib-Kinase inhibitor
Therion for PANVAC-VF-Immunotherapy
SciClone (SCLN) for RP101-Chemotherapy
Regeneron (REGN)/Sanofi-Aventis(SNY) Aflibercept-Fusion protein
ImClone/Eli Lilly for Erbitux® [cetixuimab]Monoclonal antibody
Roche Holding AG (RHHBY.PK) for Avastin® [bevacizumab]Monoclonal antibody
Aphton Corp for Insergia-Immunotherapy
Supergen (SUPG) for Orathecin-Chemotherpy
Despite past failures, drug developers continue to explore new options for treating pancreatic cancer and more than a dozen new molecular entities are currently being evaluated in clinical trials [see Table 2]. Several programs have recently demonstrated impressive results in Phase 2 studies and are now enrolling patients in pivotal trials. While a comprehensive review of investigational pancreatic cancer therapies is beyond the scope of this article, we briefly review some of the more promising pancreatic treatments currently in clinical development:
Celgene Corporation
Historically known more for its franchise in treating blood cancers, Celgene moved into the realm of solid tumors through its recent acquisition of Abraxis BioScience, Inc. As a result, Celgene is now developing Abraxane® [paclitaxel protein-bound particles for injectable suspension] for the treatment of pancreatic cancer. Updated overall survival findings from a phase I/II study of Abraxane given in combination with gemcitabine demonstrated increased survival of the first-line treatment of patients with advanced pancreatic cancer.
In 44 patients treated at the recommended dose of 125 mg/m2 Abraxane plus gemcitabine [1000 mg/m2], the median OS time was 12.2 months, an impressive doubling of survival compared to historical control of gemcitabine administered alone. The findings were discussed at the 101st Annual Meeting of the American Association for Cancer Research [AACR] in 2010. The combination of Abraxane and gemcitabine is now the treatment arm of a randomized Phase 3 clinical trial that is currently enrolling patients [ClinicalTrials.gov identifier NCT00844649].
Novartis AG
In June 2010, at the 12th World Congress on Gastrointestinal Cancer, Novartis reported that its RADIANT-3 Phase 3 study of Afinitor® (everolimus), plus best supportive care met its primary endpoint, showing that the drug more than doubled median progression-free survival [PFS], or time without tumor growth, from 4.6 to 11.0 months when compared with placebo in patients with advanced pancreatic NET.
More recently, Novartis presented data from a second Phase 3 study called RADIANT-2 at the 35th European Society for Medical Oncology [ESMO] Congress. The study, which evaluated Afinitor® in combination with Sandostatin® LAR Depot (octreotide acetate for injectable suspension), demonstrated that everolimus plus octreotide LAR provided a clinically meaningful extension in the median time without tumor growth from 11.3 to 16.4 months when compared with placebo plus octreotide LAR. However, the study did not meet its primary endpoint of PFS based on central radiologic review of the data (p=0.026 versus p=0.024 predefined). According to the company, results from the two RADIANT trials will form the basis for regulatory filings later in 2010.
Amgen, Inc.
Amgen is developing AMG 479, an investigational fully human monoclonal antibody that targets type 1 insulin-like growth factor receptor [IGF-1R], which plays an important role in the regulation of cell growth and survival. At the 2010 American Society of Clinical Oncology [ASCO] Annual Meeting, Amgen announced results from a Phase 2 study demonstrating that the addition of AMG 479 to gemcitabine resulted in an overall survival rate at six months of 57% versus 50% with gemcitabine alone and 39% versus 23% at 12 months. Median overall survival was 8.7 months versus 5.9 months in the gemcitabine arm. AMG 479 is moving into a Phase 3 study for metastatic pancreatic cancer.
Threshold Pharmaceuticals, Inc.
At the 2010 ASCO Annual Meeting, Threshold Pharmaceuticals presented results with its hypoxia-activated prodrug, TH-302, in combination with gemcitabine in thirty-four patients with advanced or metastatic pancreatic cancer that had at least one evaluable post-treatment tumor assessment. One patient [3%] demonstrated a complete response as measured by RECIST [Response Evaluation Criteria In Solid Tumors] and 8 patients [24%] had a partial response. Of the 34 assessed patients, 28 had elevated carbohydrate antigen CA19-9 levels at baseline and 17 of 28 [61%] had a CA19-9 reduction of greater than 50%. This is important, as a greater than 20% decrease in levels of this tumor-associated antigen has been shown to correlate with improved overall survival. The biomarker CA19-9 has been shown to be highly specific and sensitive for pancreatic cancer and approximately three-quarters of all pancreatic cancer patients have elevated baseline serum CA19-9 level at baseline.
Neogenix Oncology, Inc. (private)
Neogenix Oncology is develping ensituximab, a novel, chimeric monoclonal antibody intended for the treatment of advanced pancreatic and colorectal cancer. Pre-clinical studies have demonstrated that NPC-1C specifically targets pancreatic and colorectal cancer sparing healthy tissue. In 2010, the company initiated a multi-center Phase 1 trial in patients with late stage pancreatic or colorectal cancer being conducted at Johns Hopkins University Hospital, Duke University Medical Center, and North Shore University Hospital. Neogenix is also exploring the diagnostic and prognostic utility of ensituximab using a new serum ELISA test in a prospective study. Preliminary results demonstrate that the biomarker test can differentiate between blood serum of healthy donors and that of patients with colorectal or pancreatic cancer. In addition, the results of the biomarker test indicate superior sensitivity as compared to commercially available CEA and CA19-9 assays.
Table 2. Select Pancreatic Products in Active Clinical Development*
Company Product Class Stage
Celgene (CELG)/Abraxis for Abraxane-Chemotherapy Ph3
Novartis AG(NVS) for Afinitor®(everolimus)Signal transduction inhibitor
Amgen (AMGN) for AMG 479 -Monoclonal antibody Ph2
Threshold (THLD) for TH-302 in Chemotherapy Ph2
Oncolytics Biotech (ONCY)for Reolysin® Reovirus Ph2
Celgene (CELG)/GlobeImmune for GI-4000-Targeted molecular immunotherapy Ph2
Pharmacyclics (PCYC) for PCI-27483-Signal transduction inhibitor Ph2
BioSante (BPAX) for GVAX Pancreas Vaccine-Immunotherapy Ph2
Novartis AG (NVS) and Bayer Schering Pharma AG (BAYRY.PK)
Vatalanib (PTK787/ZK-222584)-Kinase inhibitor Ph 1/2
Infinity Pharma (INFI) IPI-926 Signal transduction inhibitor Phase 1b/2
Immunomedics (IMMU)for Clivatuzumab tetraxetan, 90Y-hPAM4 Monoclonal antibody – radiolabeled Ph 1b
Neogenix Oncology (private) for Ensituximab, NPC-1C-Monoclonal antibody Ph1
Seattle Genetics (SGEN)/Astellas Pharma (ALPMY.PK) for ASG-5ME-Monoclonal antibody – drug conjugate Ph1
Celldex Therapeutics (CLDX) for CDX-1307-Monoclonal antibody Ph1
* Based on ClinicalTrials.gov
Conclusion
In contrast to the prominent late-stage failures over the past five years, several drugs have recently shown promise for the treatment of pancreatic cancer. Going forward, early detection using biomarkers, more effective treatments, and novel drug targets could provide new hope for the treatment of this deadly disease.
Disclosure: No positions
Please click here to read MD Becker Partners' legal disclaimer.
About the author: Michael Becker
Mr. Becker has more than 15-years of experience as a serial entrepreneur, C-level industry executive, drug developer, Wall Street securities analyst and registered financial advisor. He is also an online communications pioneer, popular blogger, and a sought-after speaker at industry events.... More
My added comments below
http://clinicaltrials.gov/ct2/show/NCT00753038?term=reolysin&rank=8
Detailed Description:
Pancreatic cancer remains one of the most lethal cancers, ranking as the fourth leading cause of cancer death for both men and women. The American Cancer Society estimates that 37,170 men and women (18,830 men and 18,340 women) will be diagnosed with pancreatic cancer and 33,370 men and women will die of pancreatic cancer in 2008.
Activating KRAS mutations are the most frequent genetic abnormalities in pancreatic cancer (occurring in 75% to 95% of patients).
REOLYSIN has been demonstrated to kill a wide variety of cells with mutations along the RAS pathway, including pancreatic cancer cells.
The Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN given intravenously in combination with gemcitabine every 3 weeks in patients with advanced pancreatic cancer.
Response is a primary endpoint of this trial. Tumors will be evaluated by CT scan within 14 days of starting treatment, then at 6 weeks, and then every 6 weeks thereafter.
The safety of the gemcitabine and REOLYSIN combination will be assessed by the evaluation of the type, frequency and severity of adverse events, changes in clinical laboratory tests, immunogenicity and physical examination.
Patients may continue to receive therapy under this protocol, provided he/she has not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.
Data from U.K. Colorectal Cancer Study Presented in Spain
at the International Symposium on CTL and Immunostimulation
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-prnews-2889309898.html?x=0&.v=19
This is the study that led to the program that Dr Sanjay Goel used as a basis for his trial of Reolysin in combo with chemotherapy (folfiri) for RAS+ Colorectal cancer . This trial demonstrates that liver mets can be targeted by systemic delivery of Reovirus in just two to three weeks after treatment.
CALGARY, Oct. 26 /PRNewswire-FirstCall/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC.to - News) announced today that interim data from a U.K. translational clinical trial (REO 013) investigating intravenous administration of REOLYSIN® in patients with metastatic colorectal cancer prior to surgical resection of liver metastases was presented at the International Symposium on Cytotoxic T-lymphocytes (CTL) and Immunostimulation being held in Pamplona, Spain. The presentation was given by principal investigator Professor Alan Melcher of Leeds Institute of Molecular Medicine, University of Leeds, UK.
The trial is an open-label, non-randomized, single centre study of REOLYSIN given intravenously to patients for five consecutive days in advance of their scheduled operations to remove colorectal cancer deposits metastatic to the liver. Patients were treated with intravenous REOLYSIN at 1x1010 TCID50, one to three weeks prior to planned surgery. After surgery, the tumour and surrounding liver tissue was assessed for viral status and anti-tumour effects.
On histological analysis of six patients to date, there was evidence of replication and tumour cell death in the tumours of four of six patients, two of which had confirmed Kras mutations in codon 12 (the most common ras mutation). The other two of these four patients' samples were still being analyzed for Kras status. There was no evidence of replication in samples analyzed from two of the six patients. The researchers concluded that reovirus can be successfully delivered specifically to colorectal liver metastases following intravenous administration as a monotherapy and that pre-operative treatment was safe, suggesting that application of oncolytic viral therapy can be widened to the neoadjuvant setting. Further translational studies with biological endpoints, particularly co-administering reovirus with chemotherapy, would further inform how to maximize the efficacy of this novel biotherapy in cancer patients.
"This compelling data shows that following even a single course of treatment with REOLYSIN that reovirus can target and replicate specifically in metastatic colorectal cancer tumours and that there is a correlation with Kras status," said Dr. Brad Thompson, President and CEO of Oncolytics. "The interim findings from this study are further supportive of our decision to conduct a Phase I study of REOLYSIN in combination with FOLFIRI in patients with oxaliplatin refractory/intolerant Kras mutant colorectal cancer."
Published in the Journal of Clinical Investigation 05/03/2010
Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860921/
One body of work that is ongoing Im guessing Roche/Genentech may be giving more attention to is to combine Reolysin with Avastin now that Avastin has had some recent setbacks.
Timothy Kottke,1 Geoff Hall,2 Jose Pulido,1,3 Rosa Maria Diaz,1 Jill Thompson,1 Heung Chong,4 Peter Selby,2 Matt Coffey,5 Hardev Pandha,6 John Chester,2 Alan Melcher,2 Kevin Harrington,7 and Richard Vile1,2,8
1Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA. 2Cancer Research UK Clinical Centre, St. James’ University Hospital, Leeds, United Kingdom. 3Department of Ophthalmology and Ocular Oncology, 4St George’s Hospital Medical School, Tooting, London, United Kingdom. 5Oncolytics Biotech Inc., Calgary, Canada. 6Department of Oncology, University of Surrey, Guildford, United Kingdom. 7The Institute of Cancer Research, London, United Kingdom. 8Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
Address correspondence to: Richard Vile, Mayo Clinic, Gugg 18, 200 First Street SW, Rochester, Minnesota 55905, USA. Phone: 507.284.3178; Fax: 507.266.2122; E-mail: vile.richard@mayo.edu.
Authorship note: Kevin Harrington and Richard Vile are co–senior authors.
Received October 14, 2009; Accepted January 27, 2010.
Clinical trials of oncolytic virotherapy have shown low toxicity and encouraging signs of efficacy. However, it remains critically important to develop methods for systemic viral delivery if such therapies are to be clinically implemented to treat established tumors. In this respect, much effort is being focused on combining oncolytic viruses with standard treatment modalities such as inhibitors of VEGF165 (an alternatively spliced isoform of VEGF-A) signaling, which are widely used to treat several different cancers. Here, we have demonstrated that combining VEGF165 inhibitors with systemic delivery of oncolytic viruses leads to substantial regression and cure of established tumors in immunocompetent mice. We have shown that manipulating VEGF165-mediated signaling by administering VEGF165 to mice harboring mouse melanoma cells that do not express VEGF165 and by administering a VEGF inhibitor and then withdrawing treatment to allow VEGF levels to rebound in mice harboring mouse melanoma cells expressing VEGF165 allows tumor-associated endothelial cells transiently to support viral replication. This approach led to direct tumor cell lysis and triggered innate immune–mediated attack on the tumor vasculature. It also resulted in long-term antitumor effects, even against tumors in which viral replication is poorly supported. Since this combinatorial approach targets the tumor endothelium, we believe these data have direct, wide-ranging, and immediate clinical applicability across a broad range of tumor types.
Notes from Bio Investor conference - Brad Thompson CEO - Oct 6, 2010
Thanks PDT for the notes...ny emphasis
- phase III "about to start enrolling in Canada"
- Reolysin is a "selective, directed cytotoxin"
- "there's an interesting follow-on maintnenance component in the study that after the 8 cycles of the triplet, patients are then eligible for Reolysin monotherapy for as long as they are responding and a number of our collegues think that actually that might be a larger long term market for this particular product in this indication than actually the primary therapy"
- "Jan Vermorken who is listed on this slide is about to publish a study that he did on truely refractory patients and that's coming out with a median survival of almost exactly four and a half months"
- "the liver function did return to normal and usually does in all of these cases"
- "our recently announced ovarian study that we are doing in collaboration with the Gynocological Oncology Group, or GOG, and the National Cancer Institute. It's a phase II study, 150 patients, 1 to 1 weighting between the control and the test arm, so it's pactitaxel vs. paclitaxel and Reolysin and we expect that to start enrolling sometime this fall and with your typical GOG site number being around 30 or 30+ sites, so we expect primary enrollment in this study to take hopefully a little less than a year. We're quite pleased about this, it's our second randomized study, but it's also paid for by the NCI but run by the GOG"
- NSCLC - "currently enrolling in 5 centers here in the United States and we hope to have an update on that sometime this year"
- Colorectal - "half not eligible for the standard of care...should be starting any day now, a quick phase I study looking at FOLFIRI and Reolysin, and then we'll proceed into a randomized phase II study immediately thereafter. We've had very good response rates in colorectal with Reolysin as a mono-therapy and metastatic colorectal cancer in a number of our studies and so anticipation is that the addition of the FOLFIRI will simply enhance that, especially with the pre-screened patient population"
- Pancreatic - "generally accepted number is somewhere between 90 and 100% of pancs are RAS activated" - "hope to be reporting on this particular study before the end of the year"
- "one of these three studies that I've just talked about should form the basis for our next randomized study and that will just be based on data readouts"
- "currently with the NCI enrollments and from the other studies that we have ongoing we are just under 400 patients"
- "we don't see tox stacking with other agents" - "it's a very versatile agent with respect to being used with other agents"
- "a single 100 litre run produces 125,000 I.V. dosages, in that range, which gives you a cost of goods we anticipate to be a percent or less of selling cost which is, for a biologic, very good"
- "shareholder base is relatively evenly distributed between the United States, Canada, and Europe. We're about a third institutionally held and two-thirds retail"
E&OE
More Interesting Syngas data
At the end you have some comparable data for Chinese coal but we have some unit issues I have to do some calcs to compare... Btu/# and different measurement systems to conetnd with ... LLV vs HHV makes it even more fun.
http://www.netl.doe.gov/publications/proceedings/04/nox/j01.55adams-presentation.pdf
Also looking in Wikipedia, at
http://en.wikipedia.org/wiki/Lower_heating_value
The lower heating value (also known as net calorific value, net CV, or LHV) of a fuel is defined as the amount of heat released by combusting a specified quantity (initially at 25 °C or another reference state) and returning the temperature of the combustion products to 25 °C.
LHV calculations assume that the water component of a combustion process is in vapor state at the end of combustion, as opposed to the higher heating value (HHV) (a.k.a. gross calorific value or gross CV) which that assumes all of the water in a combustion process is in a liquid state after a combustion process.
The LHV assumes that the latent heat of vaporization of water in the fuel and the reaction products is not recovered. It is useful in comparing fuels where condensation of the combustion products is impractical, or heat at a temperature below 150 °C cannot be put to use.
By contrast, the HHV includes the heat of condensation of water in the combustion products.
Heating values for selected fuels[1],[2]
The first value is HHV the second is LHV, the third is a ratio of HHV/LHV and the last column is LHV/HHV
Coal [note 1] 34.1 33.3 1.024 0.977
CO 10.9 10.9 1.000 1.000
Methane 55.5 50.1 1.108 0.903
Natural gas 52.2 47.1 1.108 0.903
Propane 48.9 45.8 1.068 0.937
Gasoline 46.7 42.5 1.099 0.910
Diesel 45.9 43.0 1.067 0.937
Hydrogen 141.9 120.1 1.182 0.846
Looks like coal is about 65% the heating value of Natural Gas so coal would be about double that of Syngas.
Ninja, Im not sure quality means heating value.
Syngas and CO2
I was looking up some reference on Syngas and came across this book on Syngas combustion which describes the relationship between Syngas and Natural Gas and you can see that Syngas has a heating value of 12.24 MJ/Nm3 compared to 35.58 for Natural Gas so its about 1/3 the heating value along with 20x the CO2 of Natural Gas so thats a whopping 60x the CO2 if you equalize the amount you have to burn to equal Natural Gas.
Maddogs do you know comparable values for coal?
And a question I have, does the CCTI process work with Syngas fired plants as well as coal?
http://books.google.com/books?id=qNTPbVCzx9MC&pg=PA187&lpg=PA187&dq=carbon+emissions+from+syngas&source=bl&ots=kuk6leKKL6&sig=YN5KJR-LHU08Sg0hOfqvPQxuXjw&hl=en&ei=Y4CuTOOHHYGKlwfl-rHlDw&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBYQ6AEwAA#v=onepage&q=carbon%20emissions%20from%20syngas&f=false
China Buys Clean Coal Technology From U.S. Manufacturer
There are many interesting processes being developed and tested to address carbon capture.... This one has a saleable technology now that does not burn coal but superheats it to 1400F to seperate the coal into two pieces, Syngas and an Inert activated carbon material with lots of contaminants that can be reliquified into oil ... see www.bixbyenergy.com/technology/what-is-the-Bixby process for a good description. They make some very interesting claims about conversion of coal fired plants to this process at the bottom of the page.
China Buys Clean Coal Technology From U.S. Based Manufacturer
10/06/2010
http://enr.ecnext.com/coms2/article_inpi101006ChinaCleanCo
By Manuela S. Zoninsein
Even as it assumes the mantle of world’s largest emitter of greenhouse gases and world’s largest consumer of energy, China is taking early steps to integrate “clean coal” technologies into its energy production mix. Bixby Energy Systems, a Ramsey, Minn.-based company coming to be known for a new coal-to-gas technology, recently signed contracts to install its synthesizers in several locations throughout China and shipped its first unit to the country on Sept. 10.
In July, the China Metallurgical Group, a state-owned company involved in engineering, procurement and construction announced an agreement with Global Partners United to build coal-to-gas facilities throughout the country. GPU is strategic partner, sales agent and licensee for Bixby in China. Bixby will provide a team of engineers to help install its systems, five contracts for which have been signed and include a glass-coking factory in Changzhi in Shanxi province and four that will go to Inner Mongolia province and include a methane-production plant, a state-owned heating company and two separate chemical factories.
Robert A. Walker, founder and CEO of Bixby, says the company is expected to earn $25 million in revenue in 2010 from leasing equipment in China‹its first customer nation. The company says many companies and countries have visited its demonstration plant, and that it is negotiating with numerous potential customers.
Bixby Energy uses a process to convert coal into synthetic natural gas, cutting carbon-dioxide emissions by up to 65% below the level from burning coal, says the company.
The process superheats coal in a closed-loop environment to produce synthetic natural gas that can be used for boiler fuel or energy to spin the turbines at electrical generating stations. No carbon emissions are released into the air, the company says. The system separates the coal into syngas and semi-activated carbon that has commercial value.
The Bixby modules are 15 ft long, 10 ft wide and 50 ft high. Each can process 192 tons of coal a day and create enough gas to produce about 6.25 MW. Each module has been estimated by outside analysts to cost $4 million, though the company will not release that information. Bixby expects to receive its patent within the coming year, Walker says.
Coal-to-gas technologies can provide a bridge to cleaner coal until carbon capture and storage plants are commercial. According to John Shi, CEO of Arreon Carbon, “to reduce GHG emissions, coal-to-gas is an important component. Maybe technologies like solar and wind, these can compete on a commercial scale, be cheaper then coal; but that is like a decade away, so in the meanwhile we have to deal with coal.”
“The Future of Coal,” a study published by the Massachusetts Institute of Technology in 2003, predicted that the first full-scale commercial carbon capture and storage plant wouldn't come on-stream until 2030.
China is the world’s largest producer and consumer of coal, which generates 70% of the nation's electricity. With 114.5 billion short tons of recoverable coal reserves‹the world’s third largest after the U.S. and Russia, according to the U.S. Energy Information Administration‹China is coal self-sufficient. China has little natural gas and has said it is committed to approaching natural resource independence, so clean coal technologies have caught the attention of the Communist Party there.
Walker sees China’s reliance on coal as a “win-win” opportunity. “They have one of the world's largest coal supplies,” he said. “With that and our technology, they have domestic gas independence.”
He also points to a strong commitment to clean technology in China, where politicians and businesspeople “are anxious to be proactive about it.”
Arreon Carbon’s Shi urges this is “a very important field with quite a bit of activityŠthere’s a lot of interest out there and Chinese companies recognize the importance of this technology.” However, as Chinese companies already know a lot, and arguably have better technology than U.S. companies, “finding a good match [for a joint venture]that’s the challenge.”
GPU said several months ago that it has a letter of intent for 100 systems after completion of Bixby's demonstration plant in Shaanxi.
Dr Thompson presents Tuesday at BIO Investor Forum
http://finance.yahoo.com/news/MEDIA-ADVISORY-Oncolytics-prnews-598622979.html?x=0&.v=6
Press Release Source: Oncolytics Biotech Inc. On Monday October 4, 2010, 7:30 am EDT
CALGARY, Oct. 4 /PRNewswire-FirstCall/ - Dr. Brad Thompson, President and Chief Executive Officer of Oncolytics Biotech Inc. (TSX: ONC, NASDAQ: ONCY), will present a corporate overview of the Company at the 9th Annual BIO Investor Forum on Wednesday, October 6th, 2010 at 8:00 a.m. PDT. The conference takes place on October 5th and 6th at the Palace Hotel in San Francisco, CA.
A live audio link to the webcast presentation is available at: http://www.veracast.com/webcasts/bio/investorforum2010/39203467.cfm
or on the company's website at www.oncolyticsbiotech.com. It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN(R), its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
DrSanjay Goel on Unmet cancer needs and Reolysin
http://www.indusbusinessjournal.com/ME2/dirmod.asp?sid=&nm=&type=Publishing&mod=Publications::Article&mid=8F3A7027421841978F18BE895F87F791&tier=4&id=29D6D9E06C61487F98313F6C4F3FAAA8
Industrial Business Journal
Issue Date: October 2010, Posted On: 10/5/2010
NY doctor wins funding for cancer work
Cancer foundation $450K will let Goel continue research
By Martin Desmarais
Goel BRONX, N.Y. — Everybody enjoys getting an award, but for Dr. Sanjay Goel his recent honor from the American Society of Clinical Oncology Cancer Foundation, and the $450,000 that goes along with it, means only one thing — that patients may someday soon get a chance to benefit from the medical research he is doing.
Goel is a medical oncologist and researcher at Montefiore Medical Center and Albert Einstein College of Medicine in the Bronx. He is specifically working to test a drug for treating colorectal cancer, a drug that is not approved for use yet but Goel has high hopes for.
This past summer Goel was presented with The American Society of Clinical Oncology Cancer Foundation's Advanced Clinical Research Award for his patient-oriented approach to colorectal cancer research. He received the award at the 46th Annual Meeting of the American Society of Clinical Oncology in Chicago in June.
The foundation grants and awards provide research funding and career-developing support backing its commitment to supporting both clinicians and research in oncology practice. Goel was one of three recipients of the Advanced Clinical Research Award, which is presented annually to physicians who have five to 10 years of experience and are full-time faculty members in a clinical setting at an academic medical center. Each winner receives a three-year award totaling $450,000 to support original research that is currently not funded.
Goel received the award for his research project entitled, "A Novel Pharmacogenomic Based Therapeutic Approach for Patients with KRAS Mutant Metastatic Colorectal Cancer (mCRC) Using an Oncolytic Reovirus." Colorectal cancer is responsible for 50,000 deaths annually, with the median survival of patients with the metastatic disease only 24 months.
As Goel describes his work, he is looking to validate a drug from Canadian company Oncolytics Biotech Inc. called Reolysin because his research has shown that it can fight cancer in patients that other, more common colorectal cancer drugs do not work on.
According to Goel, in colorectal cancer patients 40 percent have been found to have a mutant gene called KRAS, which when present stops the two main available colorectal cancer drugs from working. Goel has spent the last two years trying to figure out, as he puts it: What happens to these patients?
Goel is not satisfied with the answer that they are out of luck and his research has backed the use of what is called a reovirus in the treatment of colorectal cancer patients with the KRAS mutation. Reovirus is an acronym for Respiratory Enteric Orphan virus, which is generally believed to inhabit the respiratory and bowel systems in humans. Reovirus is found naturally in sewage and water supplies. The disease has no symptoms and has been shown to kill cancer.
Goel plans to use his $450,000 in award money to run clinical trials and do more work on proving the reovirus and Reolysin is a valid option to treating to colorectal cancer and needs to be approved for patient use. "Right now, if a patient has a mutation he or she is losing out on an opportunity to have another line of therapy," he said. "That is why I feel there is a big unmet medical need.
"It is a good option and it is worth approaching," he added. "It is one of the few options that one can use to treat these patients and unless it is tested we will never know."
And for him the award money from The American Society of Clinical Oncology Cancer Foundation is a life-saver in his quest to continue his research on reovirus. "It has been a tremendous help," he said. "What this means is I can continue working on this • I can expand on this • It is a big boost."
Goel's Montefiore Medical Center and Albert Einstein College of Medicine is equally enthused about his recognition and the funding to continue this work.
"I am delighted that the American Society of Clinical Oncology Foundation has recognized and decided to support the innovative talent of one of our most promising young clinical investigators for work that expands the treatment options for patients with colorectal cancer," Roman Perez-Soler, chairman of medical oncology at New York-based Montefiore and director of the division of medical oncology at Albert Einstein College of Medicine, said in a statement.
Montefiore, which provides over 85,000 inpatient stays annually through four hospitals and serves the nearly 2 million residents of the Bronx, New York, and nearby Westchester County, is the university hospital for Albert Einstein College of Medicine. It provides clinical education and training programs, including clerkships for 750 Einstein medical students and graduate medical education for 1,000 residents and fellows. Montefiore and Einstein are focused on advancing clinical research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients, according to the organization. They feature centers focusing on cancer care, cardiovascular services, pediatrics, transplantation and neurosciences. Montefiore and Einstein are among 38 academic medical centers nationwide to be awarded a prestigious Clinical and Translational Science Award by the National Institutes of Health.
Goel has been at Montefiore and Einstein for eight years.
He received his medical degree from Christian Medical College in Vellore, India, where he also completed an internship. He came to the United States in 1996 and served his residency in internal medicine at the State University of New York Health Sciences Center and completed fellowships in hematology and oncology at the University of Colorado Health Sciences Center at Denver, and the Montefiore/Albert Einstein program.
Goel is board certified in internal medicine, hematology and oncology.
According to Goel, he has always been interested in pharmacology and drug development and working at the intersection of academia and patient care. He has an admitted passion for research and lab work. "I find academic medicine very rewarding," he said.
Though Goel does treat patients at Montefiore, he said he never envisioned himself running his own private practice because he wants to be able to treat patients but also do research.
The opportunity to do lab work on colorectal cancer early in his professional career exposed him to a field which he describes as having "so much going on" and helped steer him into an emphasis in oncology.
Transcript of the JMP Securities ONCY Presentation
Corporate Presentation by CEO Brad Thompson at JMP Securities Healthcare Conference – Sep 28, 2010
Thanks to PDT on V2 again for the effort to transcribe the presentation. You can use the Sept 24th investor presentation to see the slides
http://www.oncolyticsbiotech.com/pdf/ONCY_Investor_Presentation_Sept_24_2010
Moderator: Unfortunately Oncolytics isn’t a company that I currently cover, so I can’t make an investment recommendation, but it is a pleasure for me to introduce Brad Thompson who is the company’s CEO, Brad...
Brad: Thanks Charles. Today I’ll be doing an abbreviated version of what I normally talk about in order that Charles and I can talk about it afterwards so I’ll be cutting off a little earlier than people are normally used to me doing.
I’ll just draw your attention to our forward looking statements. We trade both on Nasdaq and on the Toronto Stock Exchange and I’d like to draw you to recent filings with the Securities and Exchange Commission and the unfortunately thirteen relevant commissions in Canada. Someday we’ll consolidate I hope.
Just very briefly, we’re an oncology company and we are looking at a product, at least at the clinical stage right now, called Reolysin and what we’re drawing people’s attention to right now is that we’ve actually been enrolling in our first phase III study, and we’re looking at platinum refractory head and neck patients and we’ve actually enrolled patients in the U.S., the U.K., and Belgium and we have approval to run this study in Canada as well, and we are just getting the sites up and running there.
We also have a randomized phase II approved that the NCI will be running for us, looking at Reolysin in combination with Paclitaxel and a number of single arm studies in a variety of interesting areas that will be reporting between now and next spring.
Our I.P. base is, I think, fairly robust. Today we actually announced composition of matter claims being approved and we are already manufacturing at the low end of commercial scale which for a live biologic is an interesting exercise I have to tell you.
What Reolysin contains is a virus, it’s a live agent, and the virus that it has is called the reovirus. For those of you who are interested it’s a double-stranded RNA virus and it’s a very common environmental virus. It’s raining today here in New York, on and off, so when we walk outside we’re actually splashing reovirus on your pant leg or on your leg if you are wearing a skirt. It’s a pan-mammalian virus so it cross infects all mammals quite readily so when you look for evidence of infection anywhere between 70 and 100 percent of adults of any species, mammalian species, have neutralizing antibodies against the virus and about half of paediatric cases of human, anyway, have neutralizing antibodies. But despite this, it’s asymptomatic in humans. Actually the vast majority of viruses are, they don’t cause pathology in humans, and that’s why they haven’t been studied. The reason it’s of interest to us as potentially a therapeutic is it has an absolute selectivity for growing in cells that have the RAS growth pathway constitutively activated and this is what actually drew me personally to this particular project as it, unlike some of our older chemotherapeutics, has at least the potential to be broadly active against pretty much a majority of any cancer. If you look at the primary carcinomas, anywhere between two thirds and 75% of breast, of ovarian, of prostate, of non-small cell lung, and so on, have a RAS pathway involvement and interestingly enough the vast majority of metastatic disease – somewhere between 90 and 100% also has a RAS pathway. So at least going in we had the possibility of actually having an agent that was broadly applicable at a much higher rate than had normally been seen before and of course, that translates into a very large patient load that actually develop cancers every year that actually develop cancers every year that have a RAS pathway involvement.
This is our current pipeline today, I’ll just be talking about two components of it to allow time for a little chatter after and so, first of all, I’d like to talk about our head and neck program which is, just as I said, starting our first phase III study and that’s looking at Reolysin in combination with carboplatinum-paclitaxel or carbotax as we normally call it. It’s a two stage phase III study, double blinded which means of course that the control arm is getting carbotax saline instead of carbotax Reolysin and it’s in 4 jurisdictions now and is likely to expand to 6 different countries by the time we are finished. We are using adaptive stats in the second part of the study so the range of patients in the second part of the study is a range of 100 to 400 patients and the primary endpoint is overall survival. With head and neck cancers, at least with this patient group, we’ve demonstrated a statistically significant linkage between survival and response rate which I think will be useful for the data readouts certainly in the first stage of the study next year. The first stage is 80 patients which will be finished enrolling in the first half of next year comfortably and which will be immediately followed by the second stage which has that range.
Now the reason that we are interested in this particular patient group falls out of work we did in the phase II environment. Head and neck is a little difficult to tease out response rates and survival rates because there usually is a mixture of patients historically enrolled in early studies and this is, for anybody who is working in this area is very familiar, is the differences between platinum refractory and platinum failed. There is a combination of agents used in radiation and Erbitux is certainly making an impact in first treatment and first line therapy and so it’s very important to focus in on the patient group that you are actually looking at in your study. For us, we are looking at patients who have failed first line chemotherapy that includes a platinum; and specifically looking at platinum refractory patients which have a much more dire outcome than patients that are simply just platinum failed for example. When you look at different references out there (and you’ll see Jan Vermorken’s name here – he led the Erbitux registration study in Europe), you’ll find that typically people believe that the response rates for these patients on carbo-tax alone is a low single digit with a survival rate that is quoted anywhere between several months and four and a half months as a median. So for our control arm in our phase III study we’ve actually powered the response rate higher than that at 10%, our time to progression we’ve powered at 2 months and we’ve powered actually the median survival at 6 months which is quite a bit higher than our true expectation for the control group. If you look at our phase II data out of the U.K. – our U.S. data, preliminary data, should be out later this year, we are just finishing off I think the last patient enrolling in that study. There was 23 patients in that study – this was reported at ASCO this year that we had a response rate, a true response rate of 42% and a clinical benefit rate which is stable disease or better in just under three quarters of the patients and there was a statistically significant linkage as I said between that and survival and our survival is still – we still have patients alive in this study – but we’re running just under double the expected four and a half months survival which is 50% higher than the powered survival that we are looking at in our phase III study.
More interesting to me personally is that the responses are different, I mean the response rate is higher, yes, which is great and quite a bit higher – it’s anywhere between 4 and 10 times higher than you’d expect for this patient group but the quality of the responses is a little different. You’re seeing responses in metastatic disease whether or not you see responses in the primary tumours which is very unusual in this particular indication, but this speaks to the RAS incidence in metastatic disease.
This is just a couple of examples. On the left side, upper and lower is the lungs and there is a little micro metastasis through the lungs and we’ve cleared that out quite nicely and the primary – there’s a little thickening here, so this was still graded as a partial response but this has been stable for a very long time so in essence it is a complete response.
Liver, and this is a very common effect we see, it doesn’t really matter what the primary is, if you have liver metastasis and you treat with Reolysin you are going to get a response overwhelmingly, normally. We’ve seen this in metastatic melanomas, breast, colorectal, head and neck of course and this is the liver mass here and these large nasty looking dark spots are the tumours and you’re getting about a 95% volumetric regression of the metastatic lesions in less than 7 weeks around. This is one of those cases where the primary was a diffuse nasal pharyngeal that didn’t actually respond particularly well – it was a minor regression so you get this differential response in metastatic lesions in the way that you would like to see but it is very uncommon.
Just a couple of visual ones, people like to see these. This patient actually presented for his first radio therapy treatment when the tumour was about three quarters of this size, I’m not quite sure what he thought that was but he left it a long time. That’s larger than an ingrown hair as far as I’m concerned. And of course you get this lovely response on Reo. And I only show this one briefly just to show you how aggressively these tumours grow, this was the patient on consent, this is 17 days later and the tumour volume has tripled. And this is very typical of the patients we’ve saw on our phase II study. And of course, after 7 weeks you’ve got resolution of the tumour mass. It’s pretty nasty stuff. I try not to show these over lunch and these are actually the better ones, we’ve got a lot worse as anybody’s that’s done head and neck would know, these are not by any stretch of the imagination the worst things that you could see.
I’m going to skip talking about ovarian briefly, just to get onto this last one. It was noted by one of our investigators that squamous cell lung is where we’re seeing, or squamous cell head and neck is where we are seeing our most aggressive responses in head and neck which is very unusual, but squamous cell is also present in other indications, primarily lung and cervical. And so we started just an early stage study in squamous cell lung in which there has been some rather noticeable failures in lately out there and this is just an early patient scan and this is where I’ll stop. This is actually our first patient and I was a little surprised when somebody sent me an email telling me about my first patient as had been reported on Fox news – the investigator hadn’t bothered to tell me about it – for which we are still discussing. But this is a patient at the start and this is the entrance of the primary tumour and those are the metastatic lesions. Post two cycles is four weeks out and you had about a 70% regression volumetrically and after four cycles we’re still getting this nice regression and actually that’s a six cycle scan still showing the same thing. And we’re seeing this same thing in other patients. The interesting thing is that while you’re taking this big bulky disease and getting these nice regressions you are not getting bleeding, quite the contrary we are actually seeing – this patient was typical foamy, bloody on entrance when he was breathing, when he was sleeping in particular, which is quite common with these squamous cell patients and we’re actually in all the patients that we are seeing these responses we’re also seeing a cessation of that nasty side effect which has caused problems with other people. So we are quite encouraged by that and I think I’ll leave it at that. I could talk more but I think we’d prefer to talk about some other things.
Moderator: Fabulous, thank you Brad for your quick overview. If there are any questions from the audience just raise your hand and I’ll try to catch them. I wanted to start Brad with a couple of questions with regard to your head and neck cancer trial. You are conducting that trial under a Special Protocol Assessment. I know that it is pretty standard to seek a SPA, especially if there is a point of contention or one in which you want absolute clarity on with regards to an endpoint or a trial design. Really, what was the driver behind you seeking a SPA for this trial.
Brad: Well, we are using overall survival as an endpoint and honestly you can pretty much do anything to a patient and if you show overall survival it will get approved, I mean that’s the gold standard in oncology. The two elements that we were wanting to get a pre-read on, specifically, were the agent itself, it’s a live agent – there’s never been a virus approved for use in the United States in oncology and us and at least one other colleague company have taken this route primary I think to get the FDA to sign off on the live agent element of it, which was I think fairly significant. The second part was that we are using adaptive statistics in this study and adaptive statistics are a highly useful tool as long as they are not misused. In adaptive stats you are doing frequent reads in the second part, it’s after 100 patients and then after 50 patients after that, but we are not actually paying a statistical penalty, and the reason that we are not paying a statistical penalty is because we are not looking at the primary endpoint, we are looking at a secondary endpoint, which in this case is P.F.S., so you are paying a stat penalty on the P.F.S. endpoint but not on the primary which is your registration endpoint. You can only do that when there is a tight statistical link between the primary and secondary endpoints. As we are all aware, in oncology, in a lot of the indications there is not the best linkage between response rate, P.F.S. and overall survival. So for us to demonstrate that there was that link allowed us to use adaptive statistics but we wanted the FDA to sign off on that element as well.
Moderator: That makes sense. Did you engage some statistical consultants or was that done in house?
Brad: We used Don Berry who is (Mod: very good) one of the father’s of adaptive statistics and actually (Mod: he and his son, right?). Yeah, and actually he has educated the FDA separately from us on the use of adaptive statistical design. It’s a very interesting thing but again I think it could be misused if people don’t understand it very well and Don and his son certainly understand it better than anybody I’ve ever met.
Moderator: And you are right, they’ve spent a lot of time educating the FDA on that. It’s used more in devices, I think.
Brad: Devices and infectious disease, I mean the endpoints. I mean I’ve come from an infectious disease background which is my linkage with this technology – a little unusual, infecting people deliberately from my background, but we do it and with good effect. But in infectious disease the endpoints are nice and clear. The absence of infection is a very good surrogate for the symptomatic relief. It’s a very good tool for infectious disease studies.
Moderator: Help us understand the first efficacy hurdle within the first phase, the first 80 patients. What do you need to be seeing to continue and then, I guess, you’ll incrementally add 50 patients or 100 patients up until a certain point at which you’ve got enough P.F.S. that you’re confident that you can get to overall survival.
Brad: Yeah, it’s a rolling maturity kind of data which means it can change day by day so, if we chose to, on the day the 80th patient was enrolled we could literally do a statistical analysis but on the P.F.S. on those two groups, but you’d only have data on possibly the first two thirds of the patients. If you wait a couple of months after that to make that decision then you have much better quality data. Again, with head and neck, the vast majority of the patients in the control arm will progress in the first two months. If you waited a couple of months you’d have absolute certainty with respect to the goal there and the threshold is so low, literally if we are adding several weeks to the P.F.S. then that is statistically enough to move on. We expect to beat that rather markedly because most of the patients on the test arm should not have progressed – it’s really a - unfortunately for the patients – very low hurdle to hop. The control arm is unfortunate but necessary in these studies. There’s an interesting part in this study is that after treating 8 cycles with the triplet and if patients are still stable or better they can go onto a Reolysin maintenance therapy as a mono therapy, but the control arm will be getting saline as a mono therapy maintenance control setting. Unfortunately most of the control arm will be dead so that won’t be a big issue but you have to run the studies that way to get good data and that is what’s paramount in the long run.
Moderator: So it sounds like the first 80 patients, there’s a futility point, but it is unlikely that’ll happen and there is not a great deal of read thru in terms of the efficacy at that point.
Brad: Another great advantage of adaptive stats is that it accounts for variability in the control arm that has caused problems for a lot of studies and so we have a large grid that actually gives you different survivals and different P.F.S.’s in the control arm that will still allow you to get to an endpoint in the study. So we have it all charted out that if the control arm lives four and a half months, six months, and seven and a half months (which it won’t, but just to be sure) and we are running enough patients to ensure that we can actually demonstrate that. If we see the same data that we saw in our phase II study, and if the control arm lives like we expect it to live, it could be statistically significant after 80 patients, but we would still run patients beyond that and get the safety package up to snuff. 80 patients might show efficacy but it doesn’t show safety. The FDA is pretty specific about having adequate safety package size.
Moderator: What’s the I.P. behind Reolysin?
Brad: The I.P. process on this particular program has been interesting. We first started out with pharmaceutical use I.P., the use of Reolysin to treat neoplasia and then broader with proliferative diseases and that’s the first thing that came out. And then you start running into all the combination claims and all that sort of stuff, and that’s all progressed quite nicely. We then moved into manufacturing claims, it’s quite a specific manufacturing process and that’s been very productive for us. But most recently has been the most interesting bits, today we actually got composition of matter claims allowed or actually issued for our clinical isolate – so those claims go out to 2028. (Mod: I saw that, congratulations) For a virus that was discovered when I was two years old is kind of interesting (many more years that 30 years ago, Eisenhower was still President when this virus was discovered). But that was because our clinical isolate under some selected pressures is slightly different than the wild type and was done quite deliberately that way. But we also have the genius reovirus patented – the use of anything in that genius is also in our claim set. (Mod: interesting...) Any use of anything called the reovirus is covered by our patent estate. It’s a good patent estate so I’m quite comfortable with that.
Moderator: Well congrats on the I.P. Are there any questions from the audience?
Audience: <question on partnering>
Brad: We always had assumed that we would be partnering when we set ourselves up structurally back at the start of the company to be partnered at the right stage and we can all smile when I say this – we are actively discussing it with people. It’s always been our position to do it at the point of maximum value and I think we are rapidly approaching that particular point. A partner would be very handy not just for the dollar support but to allow us to get into some of these larger indications. I think it would be very helpful to have a partner in place prior to doing randomized studies in lung and one of the G.I. indications, either colorectal or panc that we are working on.
Moderator: Would that be a worldwide or a certain geography partnership?
Brad: You can’t cut it by indication, that’s the problem, it is the same product for everything but then there is two alternatives and we are actually talking to people who would fit into both scenarios. Some people are interested in worldwide and actually have worldwide capability which is part two of that, and there’s a number of regional players that you could slice and dice effectively, you could take the far east out, and Europe and the States, and that’s the market. The U.S. is the oncology market still, I mean over 60% of the world oncology market is U.S. sales so doing a Western European/U.S. partnership would not be harmful, that’s the vast bulk of the market.
Audience: <question on SPA and finances>
Brad: A collegue company of ours is also running a study under a SPA for which I was absolutely delighted, I’d have to say. I mean having a room full of two people is a lot nicer than a room full of one people and in our field that was nice. We did the U.S. under a SPA and the other jurisdictions we didn’t bother under a SPA because the presumption that the U.S. SPA would supersede any considerations in those other jurisdictions.
We have a little over a year of cash right now for all our planned work and we’ll be making a decision later this year about the form and timing of future capital requirements. I feel a little nebulous about that because we are working on a couple of things that are a little different.
Audience: < it IS later this year>
Brad: Well, in Canada it is very late this year. I’ve had snow up at my place in the mountains (which we share an interest in), for about a month now. Actually one of my favourite hiking passes is snowed in now already so, yeah.
Audience: <question on immune response>
Brad: Immune responses are kind of interesting in this area. We saw when we were directly injecting into tumours we saw a response rate about what I would have expected to see with RAS activation incidence. So you take a random tumour population and inject directly, you get a 2/3 response rate which is great, as a mono therapy which is pretty impressive. And we are not alone in that as you know, if you take a variety of these viruses and inject them into tumours you get nice response rates. We went to I.V. and it got cut in about half – so our immediate thoughts were about the immune system and our secondary was about tumour interface. So we did a lot of work on the immune system, found as a mono therapy you get relatively robust immune responses but sort of in the middle of the pack, it’s not hyper immunogenic and it’s not hypo, it’s right kind of in the middle. That’s one of the reasons we started doing drug combination work and radiation combination work. What you find with carbo-tax in particular is you get a 90% ablation of the immune response against the virus which is helpful. The overwhelming effect , help, is the taxane component, it makes the tumours much more permeable to the virus, and there is a number of other things that do that, the VEGF family does the same thing, radiation makes the tumours permeable to virus, and I think that has certainly boosted the response rates back up into the range of the hypothetical . I mean pretty much any combination study we get clinical benefit rates somewhere between 70 and 100% which is sort of what you’d expect to see broadly with this agent if it was effective in getting into tumours. So the immune system is a bit of an issue, but not as much as we thought, it’s a bit of a surprise, and I think the tumour permeability which is a relative of that, is more of the issue for the virus.
Audience: <question on lytic virus?>
Brad: This is an actively lytic virus in itself. It’ll kill cells in two or three days. If you put it in the NCI 60 cell panel, for example, 45 of the 60 cells in that panel it’s effectively lytic as a mono therapy.
Audience: <question on KRAS>
Brad: 100% hit rate with mutant KRAS, very high hit rate with EGFR, which of course are both signalling through that pathway. Anything that signals through the RAS pathway is a good marker for this.
Moderator: Unfortunately we are out of time Brad, so I want to thank you for sharing the Oncolytics’ story with us and to the audience for your interest. Thanks Brad.
Brad: Thanks Charles.
E&OE
ONCY Announces Issuance of Key U.S. Reovirus Patent
Oncolytics Biotech Inc. today announced that it has been granted U.S. Patent, # 7,803,385 entitled "Reoviruses Having Modified Sequences." The patent claims cover methods for making and using modified reoviruses, and pharmaceutical compositions that include modified reoviruses.
"This composition of matter patent covers the reovirus variant that Oncolytics is using in its clinical trials with patent protection extending to 2028," said Mary Ann Dillahunty, Vice President of Intellectual Property for Oncolytics.
Oncolytics has issued patents that cover methods for treating proliferative disorders using modified adenovirus, HSV, parapoxvirus and vaccinia virus in addition to an extensive patent portfolio covering oncolytic reovirus
Dr.Thompson presenting at JMP Securities Healthcare Conference
Tuesday 10AM EDT in New York
Dr. Brad Thompson, President and Chief Executive Officer of Oncolytics Biotech Inc., will present a corporate overview of the Company at the 5th annual JMP Securities Healthcare Conference on Tuesday, September 28th, 2010 at 10:00 a.m. EDT. The conference takes place from September 27th to 28th at the New York Palace Hotel in New York, NY.
A live audio link to the webcast presentation is available at: http://www.wsw.com/webcast/jmp11/oncy/ or on the company's website at www.oncolyticsbiotech.com . It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
ONCY up strong again today
Up Over 11% yesterday and strong trading today so far up 6+%
No news yet...
Anybody have any guesses?
Novel Study Using Reoviruses Against Ovarian Cancer Pushes Forward
http://www.pr-inside.com/novel-study-using-reoviruses-against-ovarian-r2130173.htm
REO - 020
2010-09-21 20:15:34 - Calgary-based Oncolytics Biotech Inc. recently announced that the Gynecologic Oncology Group (GOG) intends to conduct a randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN(R)® in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer (GOG186H).
Researchers are now investigating whether the human reovirus, when prescribed along with chemotherapy, will provide a desperately needed “one-two punch” against ovarian cancer. The news comes during the month of September, which is National Ovarian Cancer Month. The American Cancer Society estimates that 21,880 American women will be diagnosed with ovarian cancer and an estimated 13,850 will die from the disease in 2010.
Ovarian cancer accounts for about 3% of all cancers among women and ranks second among gynecologic cancers. The prognosis for patients diagnosed with ovarian cancer at the localized stage is good with a five-year survival rate of 94%; however, fewer than 15% of cases are diagnosed at this stage. The relative 10-year survival rate for all stages combined is approximately 38%.
The GOG is a non-profit national organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies.
The study has been approved and will be sponsored by the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, US National Cancer Institute (NCI), which is part of the National Institutes of Health, under its Clinical Trials Agreement with Oncolytics.
According to the lead chair on the study, Dr. David E. Cohn of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, "Ovarian cancer is typically diagnosed at the later stages, because earlier stage disease usually has no obvious symptoms. On this basis, surgical interventions used in earlier stages are often supplemented by chemotherapy; however, there are limited treatment options for patients with recurrent disease."
Dr. Brad Thompson, President and CEO of Oncolytics, says the primary objectives of the trial are to estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel with REOLYSIN to weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer, and to determine the frequency and severity of adverse events associated with treatment with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN as assessed by Common Terminology Criteria for Adverse Events (CTCAE).
The secondary objectives are to estimate the progression-free survival and overall survival of patients treated with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN, and to estimate and compare the proportion of patients who respond to the regimen on each arm of the study. The study is expected to enroll up to 150 patients.
"Oncolytics is pleased to be collaborating with the NCI and GOG as they push forward innovative research initiatives utilizing REOLYSIN. Relationships with these groups allow us to broaden our clinical program to include additional indications and, in this case, conduct our first randomized Phase II study," says Dr. Thompson.
Information on the study will be available at:
http://clinicaltrials.gov/ct2/show/NCT01199263?term=reolysin&rank=11
Detailed Description:
OBJECTIVES:
Primary
To estimate the progression-free survival (PFS) hazard ratio of the combination of weekly paclitaxel with vs without wild-type reovirus in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.
To determine the frequency and severity of adverse events associated with these regimens as assessed by CTCAE v4.0.
Secondary
To estimate the PFS and overall survival (OS) of patients treated with these regimens.
To estimate (and compare) the proportion of patients who respond to these regimens (according to RECIST 1.1 for patients with measurable disease and by CA-125 for patients with detectable disease).
To characterize and compare PFS and OS in patients with measurable disease (RECIST 1.1 criteria) and patients with detectable (non-measurable) disease.
OUTLINE: This is a multicenter study. Patients are stratified according to their platinum-free interval (= 182 days vs > 182 days) and measurable disease status (measurable vs non-measurable or detectable). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
Arm II: Patients receive paclitaxel as in arm I and wild-type reovirus IV over 1 hour on days 1-5.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
For more information, log on to www.oncolyticsbiotech.com
ONCY breaking out today
Topped so far at +8.9 on no news.
NY Times Article on Ethics of Randomized Trials
An enligtening look into the politics and realities of clinical drug development. Its a wonder that we make any progress at all with all the hurdles.
http://www.nytimes.com/2010/09/19/health/research/19trial.html?_r=2&adxnnl=1&ref=global-home&adxnnlx=1285067297-xNaLnYHXTXBdJ6+Ax8xnsQ
Growing up in California’s rural Central Valley, the two cousins spent summers racing dirt bikes and Christmases at their grandmother’s on the coast. Endowed with a similar brash charm, they bought each other matching hardhats and sought iron-working jobs together. They shared a love for the rush that comes with hanging steel at dizzying heights, and a knack for collecting speeding tickets.
Target Cancer
Trial or Error?
Previous articles in this series chronicled the first human trial of an experimental melanoma drug, exploring the challenges that face the doctors and patients through early success, relapse, and the push to collaborate on a cure.
Complete Series »
Related Series: Forty Years' War »
Related
The Mechanisms of a Controlled Trial (September 19, 2010)
Consults Blog: Ask an Expert About Melanoma (September 19, 2010)
Enlarge This Image
Monica Almeida/The New York Times
Thomas McLaughlin received an experimental melanoma drug but thought his cousin Brandon more deserving of the treatment.
And when, last year, each learned that a lethal skin cancer called melanoma was spreading rapidly through his body, the young men found themselves with the shared chance of benefiting from a recent medical breakthrough.
Only months before, a new drug had shown that it could safely slow the cancer’s progress in certain patients. Both cousins had the type of tumor almost sure to respond to it. And major cancer centers, including the University of California, Los Angeles, were enrolling patients for the last, crucial test that regulators required to consider approving it for sale.
“Dude, you have to get on these superpills,” Thomas McLaughlin, then 24, whose melanoma was diagnosed first, urged his cousin, Brandon Ryan. Mr. McLaughlin’s tumors had stopped growing after two months of taking the pills.
But when Mr. Ryan, 22, was admitted to the trial in May, he was assigned by a computer lottery to what is known as the control arm. Instead of the pills, he was to get infusions of the chemotherapy drug that has been the notoriously ineffective recourse in treating melanoma for 30 years.
Even if it became clear that the chemotherapy could not hold back the tumors advancing into his lungs, liver and, most painfully, his spine, he would not be allowed to switch, lest it muddy the trial’s results.
“I’m very sorry,” Dr. Bartosz Chmielowski, the U.C.L.A. oncologist treating both cousins, told Mr. Ryan’s mother, Jan. He sounded so miserable that afternoon that Mrs. Ryan, distraught, remembers pausing to feel sorry for the doctor.
Controlled trials have for decades been considered essential for proving a drug’s value before it can go to market. But the continuing trial of the melanoma drug, PLX4032, has ignited an anguished debate among oncologists about whether a controlled trial that measures a drug’s impact on extending life is still the best method for evaluating hundreds of genetically targeted cancer drugs being developed.
Defenders of controlled trials say they are crucial in determining whether a drug really does extend life more than competing treatments. Without the hard proof the trials can provide, doctors are left to prescribe unsubstantiated hope — and an overstretched health care system is left to pay for it. In melanoma, in particular, no drug that looked promising in early trials had ever turned out to prolong lives.
PLX4032 shrinks tumors in the right patients, for a limited time. But would those who took it live longer? No one knew for sure.
“I think we have to prove it,” said Dr. Paul B. Chapman, a medical oncologist at Memorial Sloan-Kettering Cancer Center who is leading the trial. “I think we have to show that we’re actually helping people in the long run.”
But critics of the trials argue that the new science behind the drugs has eclipsed the old rules — and ethics — of testing them. They say that in some cases, drugs under development, PLX4032 among them, may be so much more effective than their predecessors that putting half the potential beneficiaries into a control group, and delaying access to the drug to thousands of other patients, causes needless suffering.
“With chemotherapy, you’re subjecting patients to a toxic treatment, and the response rates are much lower, so it’s important to answer ‘Are you really helping the patient?’ ” said Dr. Charles L. Sawyers, chairman of human oncology at Sloan-Kettering. “But with these drugs that have minimal side effects and dramatic response rates, where we understand the biology, I wonder, why do we have to be so rigorous? This could be one of those defining cases that says, ‘Look, our system has to change.’ ”
Dr. Richard Pazdur, director of the cancer drug office at the Food and Drug Administration, said in a recent interview that the new wave of drugs in development — especially for intractable cancers like melanoma — might require individual evaluation. “This is an unprecedented situation that will, hopefully, be increasingly common, and it may require a regulatory flexibility and an open public discussion,” he said.
And doctors say that for them, the new wave of cancer drugs is intensifying the conflict between their responsibility to their patients and their commitment to gathering scientific knowledge for generations of the critically ill.
Of course, no single pair of patients can fairly represent the outcomes of a trial whose results are not yet known. Rather, the story of Thomas McLaughlin and Brandon Ryan is one of entwined paths that suddenly diverged, with a roll of the dice.
At times beseeching and belligerent, Mr. McLaughlin argued his cousin’s case to get the new drug with anyone he could find at U.C.L.A. “Hey, put him on it, he needs it,” he pleaded. And then: “Who the hell is making these decisions?”
He believed he should trade places on the trial with Mr. Ryan, who was pursuing his contractor’s license and had just bought a four-bedroom home in Bakersfield. “Brandon has everything going for him,” he told his Aunt Jan.
Enlarge This Image
Brandon Ryan was put in a control group, and is glad his cousin Thomas is the one receiving treatment. “Tommy has the kids,” he said. “They need him around.”
Target Cancer
Trial or Error?
Previous articles in this series chronicled the first human trial of an experimental melanoma drug, exploring the challenges that face the doctors and patients through early success, relapse, and the push to collaborate on a cure.
Complete Series »
Related Series: Forty Years' War »
Related
The Mechanisms of a Controlled Trial (September 19, 2010)
Consults Blog: Ask an Expert About Melanoma (September 19, 2010)
Enlarge This Image
Angel Franco/The New York Times
AN ETHICAL DILEMMA Dr. Paul Chapman leads the PLX4032 trial, in which half the patients get the drug and half get chemotherapy. He sees a controlled trial as vital to proving whether PLX4032 prolongs lives.
But Mr. Ryan told his mother he was glad that Mr. McLaughlin, who has a young son and daughter, was the one getting the promising drug. “Tommy has the kids,” he said. “They need him around.”
Path to a Second Trial
The debate over the controlled testing of PLX4032 began in June 2009, around the time Mr. McLaughlin awakened with what felt like an explosion under his right armpit.
The drug, manufactured by Roche, the Swiss pharmaceutical giant, was designed for melanoma patients whose tumors carry a particular mutation, and the company reported that month that nearly all 32 such patients in the drug’s first clinical trial, called Phase 1, had seen their tumors shrink.
The reprieve was all too brief: most saw their tumors begin to grow again within the year. Still, The New England Journal of Medicine called the drug “a major breakthrough” for people with advanced melanoma, whose median survival is eight months after diagnosis. A second, or Phase 2, trial, aiming to validate the results in more patients, was already in the works. And in meetings that summer, several oncologists urged Roche to seek accelerated approval from the F.D.A. The agency allows a manufacturer to sell a drug based on early promise so long as it proceeds with the traditional controlled trial comparing it with the standard treatment.
But with patients already begging doctors for the drug, it seemed unlikely that anyone would join a trial with only a 50-50 chance of getting PLX4032 once it was already on the market. Unless the trial was conducted before approval, it seemed, there would be no chance to get definitive data on its effectiveness.
Some melanoma specialists familiar with the drug would have traded the data for faster access to the drug. “I know all that I need to know based on the results we already have,” said Dr. Keith Flaherty of Massachusetts General Hospital, who led the early clinical testing. “My use of this drug is not going to be informed by testing it against a drug we all hate and would rather never give a dose of again in our lives.”
The standard chemotherapy used in melanoma, dacarbazine, slowed tumor growth in 15 percent of patients for an average of two months. By contrast, PLX4032 had halted tumor growth in 81 percent of patients for an average of eight.
It was conceivable that when the cancer started up again, it would progress much faster in patients who had taken the new drug, wiping out any extra time they might have gained. But even if so, many doctors believed that if the drug provided relief by shrinking tumors — like the one Mr. McLaughlin soon learned was pressing against a nerve in his arm — that would improve their patients’ lives.
The trial, moreover, would cost $100 million and delay the possibility of F.D.A. approval by at least two years. To some doctors, it seemed a waste of time and resources that would be better used for trials testing what everyone most cared about: how to prolong the remissions.
There was reason to believe that combining PLX4032 with other drugs — some from competitors — would make it more effective. But researchers had to rely on Roche for permission until the drug was available for sale, and the company had not been forthcoming.
Dr. Chapman of Sloan-Kettering came up with a new tack: an unconventional bid to speed the drug’s approval, rooted in the observation that patients weeks or days from death could get out of bed and off oxygen when given PLX4032, sometimes for months. The doctors working with the drug referred to this as the Lazarus effect; it was unheard of with dacarbazine.
A trial that cataloged PLX4032’s effect on the well-being of the sickest patients, Dr. Chapman argued, would probably yield fast, tangible results. For him, it represented a chance to give patients symptomatic relief, even if the drug turned out not to prolong life.
“Even without a survival benefit, maybe we could show that it helps people,” he urged. “If you could get Aunt Sadie to the wedding and off of oxygen, that would be great.”
But company officials feared that might lead to approval for only a narrow group of the sickest patients. The surest way to get the F.D.A’s endorsement for a broader market was a controlled trial. And with its competitors rushing to get similar drugs to market, the findings of such a trial might give Roche an advantage in marketing its version as the only one proven to prolong survival.
Enlarge This Image
Michal Czerwonka for The New York Times
Dr. Bartosz Chmielowski, who treated the two cousins, obeys trial protocols but says withholding a drug from a patient he thinks could be helped “is awful.”
Target Cancer
Trial or Error?
Previous articles in this series chronicled the first human trial of an experimental melanoma drug, exploring the challenges that face the doctors and patients through early success, relapse, and the push to collaborate on a cure.
Complete Series »
Related Series: Forty Years' War »
Related
The Mechanisms of a Controlled Trial (September 19, 2010)
Consults Blog: Ask an Expert About Melanoma (September 19, 2010)
On Sept. 1 last year, the company submitted its plan to the F.D.A. for the traditional, randomized, controlled trial of PLX4032. It would involve 680 patients, half of them in a control group. Dr. Chapman would be the lead investigator for more than 100 sites in the United States, Europe and Australia. Because of the different ways the drugs were dispensed — one by mouth and one by infusions — doctors and patients, it was decided, would both know who got which drug.
The following week was when Mr. Ryan learned that his cousin might have a health problem. He called Mr. McLaughlin from a job site in Colorado, to tell him about his new Dodge Ram, a truck he knew Mr. McLaughlin had long coveted.
He invited Mr. McLaughlin to come stay with him: there was plenty of welding work, and he could help break in the truck. But Mr. McLaughlin, who had no health insurance, had finally visited a doctor about the pain under his arm. It was melanoma, and he would need surgery to remove some lymph nodes.
“Wow,” Mr. Ryan said, suddenly silent. “You have cancer?”
Two Men’s Struggles
Mr. McLaughlin’s surgery, it seemed, had come too late. In the weeks following, small tumors popped up across his body, including one on his collarbone and one on his triceps.
When Mr. Ryan discovered a swollen node under his own right armpit in October, his mother was not taking any chances. She begged him to go to the emergency room in Colorado. Even so, when the verdict was melanoma, both families were shocked.
Was it genes? Their mothers, after all, were sisters. But there was no history of cancer in the family.
Environment? The boys had fought, played and competed with each other since childhood: who could hold his breath the longest, do the highest cannonball dive, suck down a Slurpee fastest, win their grandfather’s approval? They had ranged across California on iron-working jobs, eating the same food, drinking the same large quantities of beer, promising, in a rare moment of seriousness, that each would bury the other with his hardhat when the moment came. Coincidence?
Compared with most cancers, melanoma strikes a disproportionate number of young people; it is the sixth most common cancer in the United States.
There was no way to know.
Last Thanksgiving, Mr. McLaughlin greeted Mr. Ryan with the usual bear hug. “Looks like we’re doing this together,” he said.
Not ones for excessively talking things over, they left it at that.
Yet both cousins, like the other family members, believed then that Mr. Ryan stood a far better chance of surviving the disease than his cousin. His cancer was rated Stage 3, with no evidence yet that it had spread to distant parts of his body. Mr. McLaughlin, at Stage 4, had a tumor ominously near his liver. And Mr. Ryan had health insurance, while Mr. McLaughlin had none.
It was the mutated gene that the U.C.L.A doctor found in Mr. McLaughlin’s cancer cells in December that turned his luck around. Called B-RAF, it goes awry in half of the 68,000 Americans who develop melanoma each year, for reasons not well understood, signaling cells to grow uncontrollably.
The mutation meant that he would be eligible for PLX4032’s new trial, so the cost of the drug and doctors’ visits would be paid by Roche. And it turned out he would get the pills even before the controlled study began, on a small test of the drug’s interaction with common drugs like caffeine and cough syrup. Judging by the response of patients to PLX4032 in the first trial, Mr. McLaughlin was almost certain to respond. But the medication, the doctors at U.C.L.A warned him, might cause a rash and fatigue and would probably make his skin extremely sensitive to the sun.
“They told me to get a job where I could be inside all the time,” Mr. McLaughlin told Mr. Ryan with a grin; perhaps no one else could better understand how ridiculous it seemed for someone who had spent his whole life outdoors.
Because the slots in the trial were reserved for patients with the most advanced cancer, Mr. Ryan was not eligible — yet. But because he had few symptoms, it hardly seemed to matter. After surgery to remove his cancerous lymph nodes and radiation, he was preparing to return to work.
“Dude, I had ALL of my lymph nodes out,” Mr. Ryan boasted to his cousin over a Mexican-style Christmas dinner at their grandmother’s home in Santa Maria, not passing up an opportunity at one-upmanship. “How many did you have out again, 11?”
Target Cancer
Trial or Error?
Previous articles in this series chronicled the first human trial of an experimental melanoma drug, exploring the challenges that face the doctors and patients through early success, relapse, and the push to collaborate on a cure.
Complete Series »
Related Series: Forty Years' War »
Related
The Mechanisms of a Controlled Trial (September 19, 2010)
Consults Blog: Ask an Expert About Melanoma (September 19, 2010)
Mr. McLaughlin, fingering the tumor that felt like a knot under his arm, might not have been in top form that evening. But he mustered a scoffing reply: “So you had all of them taken out and only four had tumors?”
The following week, he took his first pills.
But even as the tumor on Mr. McLaughlin’s collarbone began to melt away, a faint spot on Mr. Ryan’s lung began to grow.
A Life-or-Death Debate
The discontent among some oncologists over the design of the PLX4032 trial spilled over at a scientific meeting sponsored by the Melanoma Research Alliance in late February.
The ethical review boards at dozens of prestigious cancer research institutions had signed off on the trial, and the leading melanoma oncologists had embraced it: after all, it was the only way to get the most promising drug available for their patients.
But with the trial now under way, a few attending the Las Vegas meeting had already had to tell patients they had been assigned to the trial’s chemotherapy control group. And some had begun to question whether an ethical code that calls for doctors to be genuinely uncertain about which of a trial’s treatments will be more effective had been breached when it came to PLX4032 versus dacarbazine.
After Dr. Chapman presented the recent data from the drug’s promising first trial to a packed room, Dr. Neal Rosen, a friend and Sloan-Kettering colleague, stood up.
“Excuse me,” Dr. Rosen said with unusual formality. “But if it was your life on the line, Doctor, would you take dacarbazine?”
The room was silent.
“My goal,” Dr. Chapman shot back, “is to find out as quickly as possible in as few patients as possible whether this works. If we never know, then we’re never going to be able to build on anything.”
One of the melanoma field’s senior clinicians, Dr. Chapman had lived through trial after trial of drugs that failed to live up to early promise. Almost every oncologist knew, too, of a case nearly 20 years earlier when bone marrow transplants appeared so effective that breast cancer patients demanded their immediate approval, only to learn through a controlled trial that the transplants were less effective than chemotherapy and in some cases caused death.
“Making patients’ tumors go away is gratifying,” Dr. Chapman told critics. “But that’s not the business I’m in. I’m in the business of making people live longer. That’s what I want to do.”
Several of the most veteran melanoma doctors agreed with him. But others argued that oncologists had an ethical obligation to push both the F.D.A. and Roche to make the drug more immediately available.
Some of the strongest criticism came from laboratory researchers who study the biology of the disease and see the drug as fundamentally different from its predecessors. The previous red herrings, they argued, never had such a high response rate. Few other drugs had shrunk tumors in as high a percentage of patients with melanoma or any other solid tumor as PLX4032 had in its first human trial.
“Many of my colleagues who are outstanding clinical investigators have been able to convince themselves that this is a fair thing to do,” Dr. David E. Fisher, a leading melanoma biologist at Massachusetts General, said of the controlled trial. “My personal view is it’s nuts. I don’t know anyone who hasn’t shuddered at the concept that we can’t let patients on the control arm cross over because we need them to die earlier to prove this point.”
In the meantime, some doctors were searching for other trials that could help patients worsening in the chemotherapy group of the Roche trial, even at the risk of undermining its results. Several lobbied to get such patients slots on a new trial of a PLX4032 competitor, manufactured by GlaxoSmithKline.
“It’s much easier to tell patients, ‘We’ll try this for six weeks; if it’s working, great, if not, we’ll shift you right away to the other trial,” said Dr. Jeffrey A. Sosman of the Vanderbilt-Ingram Cancer Center in Nashville. “That’s how I’m going to be able to live with the randomization.”
The reason to prevent patients in the chemotherapy group from subsequently getting PLX4032 was to ensure a clean comparison. But who could prevent them from trying treatments that might well help them live longer? At least one melanoma patient left Sloan-Kettering’s care to join the Glaxo trial at New York University.
In April, Mr. McLaughlin donned a bandanna, a sun hat, a long-sleeved shirt and pants and went to a job building fences on a nearby ranch. The pills, he had vowed, would not prevent him from working outside.
Target Cancer
Trial or Error?
Previous articles in this series chronicled the first human trial of an experimental melanoma drug, exploring the challenges that face the doctors and patients through early success, relapse, and the push to collaborate on a cure.
Complete Series »
Related Series: Forty Years' War »
Related
The Mechanisms of a Controlled Trial (September 19, 2010)
Consults Blog: Ask an Expert About Melanoma (September 19, 2010)
Mr. Ryan’s health, by contrast, was declining. He returned from work only to sleep. Often, when his mother called, he was too tired to come to the phone. “Sleeping, Mom,” he would text her. Or “You have no idea what this feels like, Mom.” Or just, “I hurt.”
His doctor in Bakersfield moved up a scheduled scan.
At the same time, a debate grew heated over Roche’s decision to withhold PLX4032 from many patients not eligible for the trial because they had already been treated with chemotherapy.
The F.D.A. regularly approves such programs, known as “compassionate use,” for promising experimental drugs. But Roche feared a prospective trial candidate might undergo chemotherapy just to qualify for compassionate use and get PLX4032 with no strings attached.
In an emotional moment, Dr. Donald Lawrence of Massachusetts General Hospital e-mailed colleagues about Roche’s decision last spring, under the subject line “moral outrage.”
“Just had yet another conversation with a [patient] with a B-RAF mutation who will die in the next month or so because he can’t get PLX4032,” he wrote. “I feel we need to muster the support of our patients and lobby both Roche and the F.D.A. Compromising the Phase III trial is not justification for withholding an effective drug from dying patients.”
But Dr. Michael Atkins, director of the cancer clinical trials office at Beth Israel Deaconess Cancer Center in Boston, urged him to consider what he thought was the greater good: “Even though it is painful, I think completing a clean Phase III trial and determining if there truly is a survival benefit for PLX would have major value for the field and future patients.”
A Bitter Blow
On the morning of May 12, Mr. Ryan and his mother drove to U.C.L.A. The cancer had spread throughout his body. Yet that weekend, the family was filled with hope. Dr. Chmielowski had found the same gene mutation that Mr. McLaughlin had in one of Mr. Ryan’s tumors. He was finally eligible for the trial.
But the computer made its assignment the following Tuesday, making sure that he would not be getting his cousin’s “superpills.”
Mr. Ryan’s mother picked up the call while her son was undergoing radiation for the tumor on his spine. He was on oxygen.
“I’m sorry,” Dr. Chmielowski repeated as she cried into the phone.
There must be someone higher up to whom she could talk, she said.
There was not, he told her. It was completely random. No one could change it.
“Who else has this drug?” Mrs. Ryan demanded. “We will go wherever we have to go.”
There was nowhere to go, the doctor explained. Once Mr. Ryan had been randomly assigned to the control group at one place, the other hospitals testing the melanoma drug would not give it to him. U.C.L.A. had turned away such patients, too.
The doctor did not tell Mrs. Ryan about the Lazarus effect — that for someone as sick as Mr. Ryan, PLX4032 was probably the best chance to control his symptoms while doctors searched for something better.
The doctor could not know, of course, whether Mr. Ryan really would have fared better on the Roche drug, or whether Mr. McLaughlin’s disease would have been held in check just as well with the chemotherapy. Obeying the trial’s protocol meant withholding the drug from patients like Mr. Ryan, and that, Dr. Chmielowski would later explain, “is awful.”
He told Mrs. Ryan, if the chemotherapy could stabilize her son for just a month or so, there were two new trials opening that might help him.
“What gives them the right to play God?” Mrs. Ryan exploded at home later that night. “It doesn’t make sense to say, ‘We want you for a statistic’ instead of giving them a chance at life.”
Mr. Ryan started his infusion the next day. But a week later, he was hospitalized, unable to breathe on his own and in horrible pain.
“Bud brownies,” Mr. McLaughlin prescribed when he arrived to visit, having already signed himself up for medical marijuana use. “You get out of here, and I’ll make them for you.”
He rated the nurses, trying to make Mr. Ryan laugh.
“Maybe you should just say you want to split some of your pills with her and she’ll hop into bed with you,” he suggested after one left the room. A few minutes later, “No, that one’s a little cuter.”
Then he reminded his cousin of the time Mr. Ryan had thrown a bolt up to where he was sitting atop a wall for a welding job adjacent to a golf course. Mr. Ryan missed his mark by several feet and the bolt landed on the other side, shattering the windshield of another contractor’s truck.
“I’m like, ‘You just tagged that guy’s freakin’ truck,’ ” Mr. McLaughlin recounted for the other family members in the hospital room. On his side of the wall, Mr. Ryan had picked up a stray golf ball. “And then the guy walks out and Brandon goes, ‘Looks like those golfers hit your windshield.’ ”
In his hospital bed, Mr. Ryan was beginning to smile.
“And the guy gets in the truck,” Mr. McLaughlin finished, “and takes off for the golf course.”
Two weeks later, at his cousin’s funeral in mid-June, Mr. McLaughlin placed Mr. Ryan’s hardhat in his coffin and helped carry it to the grave.
Mr. McLaughlin has now been taking PLX4032 for nine months. He is awaiting his next CT scan.
Hopes and Prayers
http://www.techrev.ca/techrev/bins/content_page.asp?cid=9160-9175-9365&lang=
Hopes And Prayers Of Millions Around The World May Soon Be Answered By Theraputic Drug
“It’s one of those ‘smart people making observations about things they didn’t expect’ kinds of stories.”
Brad Thompson, CEO
The science that would eventually become the basis for Oncolytics emerged from the Department of Microbiology and Infectious Diseases at the University of Calgary in the mid 1990’s. At that time, Dr. Patrick Lee, along with two research assistants Matt Coffey and Jim Strong, were doing basic research on the human reovirus. They observed that this virus grows only in certain types of cell lines, specifically cancerous cells with certain metabolic defects. This was a pivotal observation and the team realized that they were working with an agent that could potentially be a therapeutic drug for cancer. They began testing the virus on animal models with the results providing confirmation of their hunch, so they decided to take steps toward founding a company to develop a therapeutic drug and Oncolytics was born.
There is no Middle Ground Once You Reach Phase III
Reovirus, an acronym for Respiratory Enteric Orphan virus, is commonly found in the respiratory and bowel systems of human beings and occurs naturally in sewage and water supplies. It has been found to be a benign virus that does not cause symptoms of illness in humans. The profile of reovirus as harmless to normal cells is an important element of Oncolytic’s proprietary formulation of reovirus, called Reolysin. Reolysin has been demonstrated to replicate and kill cancer cells, while leaving healthy cells intact. The reovirus enters cancerous cells with an activated Ras pathway, which lack the cellular protein that triggers an anti-viral response, then replicate and kill the cell.
When cell death occurs, progeny virus particles are released and infect surrounding cancer cells. This process repeats itself until no cancer cells are left. An activated Ras pathway occurs in approximately two-thirds of all tumours. Normal cells do not contain an active Ras pathway and are able to produce anti-viral defences and prevent infection.
Oncolytics has run human clinical trials using Reolysin alone and in association with radiation and chemotherapy. The company is currently heading into the final stages before Reolysin can be sold. Over fifteen years of research will culminate with the drug completing Phase III clinical trials in the next two years or so. The results of these trials will either see Reolysin approved and taking off as a cutting-edge therapeutic drug for cancer or failing and destroying Oncoytics as a company: there will be no middle ground. Oncolytics is truly a company on the brink.
“Dogged Belief”
In 1998 Brad Thompson, a microbiologist, was going through a very difficult time. He had recently lost two family members to cancer and had been diagnosed with melanoma himself. Cancer was definitely a top of mind. Interestingly, this was also the period that Patrick Lee, Matt Coffey and Jim Strong approached him about the possibility of starting a pharmaceutical company. They informed him of the results of their early research and despite the inherent instability of biotech companies, Thompson signed on. He credits his interest in virology and the fateful timing of the request for his willingness to take on the role of CEO for what would become Oncolytics.
“I think you have to be a little bit crazy, honestly, to do start-up companies in our area. The time commitment and the risk profile is really off the scale so you have to have some sort of hook to get you interested in doing this.”
“You have to have a dogged belief that what you are working on will work, because if we don’t believe it, how can anyone else and you can’t pretend belief…often with very little supporting evidence in the early days to indicate that it will work. Secondly, you have to have an equally dogged total faith that you can raise the resources and refuse to let your company fail for lack of resources and applying that belief to raising money.” – Brad Thompson, CEO From that point, Oncolytics was incorporated with founding shareholders: Brad Thompson, Patrick Lee, Matt Coffey, Jim Strong and University Technologies International at the University of Calgary. Investors in the early stages of Oncolytics were generally high net-worth individuals and subsequently, a combination of high net-worth and institutional investors and a large group of retail shareholders The company began active operations in 1999. Brad Thompson and Matt Coffey, in the role of Chief Operating Officer, were the first two employees - taking the company public together.
Oncolytics has followed an unusual business plan, though typical of biotech companies, that runs in a cycle of raising capital to fund research and then showing progress through this research in order to receive more funding. Since the development cycle for a biotech pharmaceutical is quite lengthy (Oncolytics had their 10-year anniversary in August 2009) it is imperative to maintain investor interest in the research through notable advancement. Thompson says that the motivation and drive to continuously raise funds and progress the research “is an art more than a science” and is underscored by an unwavering faith.
As Oncolytics moves into the final phase of clinical trials, Thompson is reflective on the past and enthusiastic about the future.
“It’s exciting. I mean this is what we did all of that work for and put up with all we put up with – to get to the stage where you actually get to show that it definitively works or not. It’s kinda neat – it’s one of those industries where medical need and that whole feel-good factor of coming out with something that presumably will help a lot of people – I mean if this product works the way it looks like it’s working in early clinical studies, we could be treating literally hundreds of thousands to low millions of patients every year.
That’s a lot of people to derive benefit from a disease that kills people. If that works out than you have this absolute correlation with financial success for your shareholders.”
If Reolysin proves to be successful in the next couple of years Oncolytics will begin looking at developing other drugs in a similar vein, by examining other viruses with the potential for providing cancer therapy.
Inside a clinical trial
Oncolytics runs clinical trials for Reolysin in the United States and the United Kingdom. Oncologists participating in the Phase I and II trials recruit patients from their caseloads that fit a very specific profile. The strict enrollment criteria exclude patients with brain metastasis, as they would skew the results. Using cancers of the head and neck as an example, participating patients have to have failed radiation treatment, surgery and their first drug intervention, which has to have included a platinum based drug. Additionally, patients must have the right type of cancer, along with metastatic disease and meet minimum health standards, such as being without a failing heart, lung function above a certain measure and blood chemistry that is not troubling.
The profile of a typical Oncolytics’ Phase I or II clinical trial patient is that of someone already under the care of an oncologist who has received all of the existing therapies but has not experienced the desired benefits. The oncologist decides that the patient may derive benefit from an experimental drug.
Once a patient has been recruited into the study, the Oncolytics headquarters in Calgary receives an enrollment form that includes a patient number and site number along with basic information about the patient like age and sex – names are never included. The patient number is then tracked throughout their treatment with Reolysin and their response to the drug is monitored. This monitoring goes on for as long as possible, until the patient dies.
Phase III clinical trials function quite differently as they are randomized studies that provide undisputable proof of a drug’s effectiveness. The main difference lies in the fact that not every patient will be treated with the experimental drug.
The drug regime for each trial patient is selected randomly by a computer: patients in the A group will receive the standard therapy plus the experimental drug, while patients in the B group will receive the standard therapy but only a placebo along with it. This results in two large groups that are monitored throughout treatment and the statistics should show that one group is living longer and experiencing improvements in their health. If this is the case, the experimental drug is approved and can be sold.
Contact Information
Corporate Headquarters:
210, 1167 Kensington Cr. NW
Calgary, Alberta T2N 1X7
Canada
Brad Thompson, PhD.
President and CEO
Main: +1 403-670-7377
Email: notan@aol.com
www.oncolyticsbiotech.com
Founders:
Matt Coffey, PhD.
Chief Operating Officer
Patrick Lee, PhD.
Cameron Chair in Cancer Research at Dalhousie University
Jim Strong, PhD.
Brad Thompson, PhD.
President and CEO