Oncolytics Biotech Inc. (ONCY)

[onco_investor]

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

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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.