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if the lead drug has had disappointing results to date why is the market cap so high. Is it only because it has rnai in the business plan?
Why is the time to treatment failure a better measure of efficacy than total treatment failures over the 50 day period?
if you are asking why they used the endpoint they used instead of treatment failures at 50 days I have no idea. then again, in the phase 2 orbec didn't have the problems in the first 10 days so it wasn't an issue.
At 50 days treatment failure was p value was .0515.
In the odac panel minds i think they thought the treatment failure rate was .1177. the p value of .1177 was a weighted average of the treatment failure throughout the 50 days so the problems in the first 10 days were actually magnified even though the drug didn't have a chance to take effect.
the important thing is at 50 days how many people were saved from undergoing high dose prednisone, not when they failed.
RNA Drugmakers, biotechs experiment with RNA to block diseases; risky technology could lead to multi-billion dollar industry.
By Aaron Smith, CNNMoney.com staff writer
October 10 2007: 11:25 AM EDT
I had never heard of optk
NEW YORK (CNNMoney.com) -- Biotechs and big pharma are betting billions on an experimental technology that could be a quantum leap for healthcare, or just a big bust.
They're working on treatments to harness a naturally occurring process called RNAi (the "i" stands for "interference') to block the creation of diseased cells.
Some analysts believe the technology could blossom into a multi-billion dollar industry. But it's still very experimental, and a marketable product is years away.
"Whether or not they can bring a marketable compound out of this [RNA] mechanism remains to be seen, but you can be sure it would open up the floodgates for other people trying other indications," said Les Funtleyder, analyst for Miller Tabak. "The sky's the limit, but they have to prove themselves, first."
RNA players include OPKO Health, Alnylam Pharmaceuticals, Novartis and Merck & Co. The New Jersey-based pharma giant Merck cast a major vote of confidence for this technology in 2006, when it paid $1.1 billion for Sirna, a company specializing in RNA research.
At the time, Merck was criticized for the Sirna buy, because RNAi research was still in an early phase, and the deal was seen as a huge risk.
"These are very high risk speculative investments," said Douglas Chow, an analyst for Caris & Co. He added that the Sirna deal was one of the few times that a dollar value was attached to RNA technology.
OPKO Health (Charts) and Alnylam Pharmaceuticals (Charts) possess the most advanced pipelines for injectable drugs based on RNA, the pathway used by DNA to produce proteins.
Miami-based OPKO, which has a $650 million market cap, has the world's most advanced RNAi compound in its pipeline, according to company executive vice president Sam Reich and analysts who follow the industry.
The company's bevasiranib compound is an experimental treatment for age-related vision loss, the most common cause of blindness in the developed world. This is the only RNAi drug in phase 3, the final stage of testing before submission to the Food and Drug Administration for review.
If the late-stage trials are successful, OPKO could file the first RNA drug application to the FDA in 2010, said Reich. He considers bevasiranib a potential blockbuster, which would compete with Genentech's non-RNAi drug, Lucentis, which pulled in $420 million in sales during the first half of 2007.
Alnylam, a Cambridge, Mass.-based biotech with a market cap of $1.4 billion, is not too far behind with RNAi compounds. The biotech has built its entire pipeline around this genetic process.
The company has an RNAi inhalable treatment in phase 2 testing, meaning that is has yet to enter late-stage testing and is still years away from potentially entering the market. The compound, called ALN-RSV01, would be used to block the manufacture of the respiratory syncytial virus, the leading cause of pneumonia and bronchiolitis in babies and toddlers.
Pharma giants Merck (Charts, Fortune 500) and Switzerland-based Novartis (Charts) are the biggest players developing RNAi drugs.
During a recent interview at the Novartis Institutes for BioMedical Research (NIBR), in Cambridge, Mass. President Dr. Mark Fishman said that controlling RNA to block diseases "was the next best thing we could do to fixing the gene and the DNA itself," a process that has "proven impossible so far."
"In principal, [RNA technology] could replace the drugs that are out there today, by preventing the synthesis of the protein, not just block its activity," said Fishman.
But it's going to take years to turn this "principal" into a marketable product, according to Trevor Mundel, head of exploratory clinical development for NIBR. "It'll probably take five to 10 years to get a drug on the market, with five years very optimistic," he said.
Merck, through its merger with Sirna and partnership with Allergan (Charts) is experimenting with SIRNA 027, a phase 2 treatment for age-related vision loss. It's Merck's most advanced compound in development.
"Merck is strategically focusing its scientific expertise and resources on fully realizing the potential of Sirna's RNAi technology and programs," said company spokesman Ian McConnell. "This technology is likely to be used across all of Merck's therapeutic areas."
While the experimentation with RNAi technology isn't exactly new, the interest in its applications snowballed with recent collaborations, said BWS Financial analyst Hamed Khorsand. He referred to the Merck-Sirna merger, and a deal between Isis Pharmaceuticals (Charts) and Johnson & Johnson's (Charts, Fortune 500) healthcare subsidiary Ortho-McNeil.
"It's something that companies have been working on for many years, but no one's been putting much emphasis on it until recently," said Khorsand. "Right now, everyone is trying to collect as many patents as possible."
Isis develops RNA drugs, but it uses a different process called "anti-sense," which uses an artificial mechanism, rather than the naturally-occurring pathway. Isis, a Carlsbad, Calif.-based biotech with a market cap of $1.5 billion, is developing an anti-cholesterol drug (known as 301012) that's in phase 2 clinical trials. If successful, the drug would block the creation of harmful cholesterol.
The science of RNA has broad applications, meaning that it could eventually be used to treat a myriad of diseases. But even the most bullish analysts chant the same mantra: proceed with caution.
Ding Ding, an analyst with Maxim Group, said the market for RNAi could eventually reach billions of dollars in annual sales. But she warned that "translating a great science into a commercially successful product" is time-consuming and "very risky."
The analysts quoted in this story do not own stock in the companies mentioned here.
Find this article at:
http://money.cnn.com/2007/10/09/news/companies/rna/index.htm?postversion=2007101011
I would like to make the point that odac had 3 hours to look at data that the fda has had over a year to review. There was also only one transplant specialist on the panel and he voted to approve the drug.
I am sure that Dr. Pazdur has had time to review the data showing that the treatment failure at 50 days showed that there were 30 treatment failures on placebo and only 18 failure on orbec with a p value of .0515. The panel never saw that data. It was in Dor's briefing document but I am pretty sure the panel never looked at that. they were probably more interested in the idm data
you are buying mcu at a good price but there is a going to be a tremendous overhang.
the financing they did at 1.15 pissed off a lot of people including me
DORb: What good is an "expert opinion," if the FDA/FDA Advisory Committee doesn't agree with the experts?
when it is on the market because the fda believes is works then dor will have marketing materials from the experts
orBec(R) Clinical Summary Published in "Expert Opinion on Investigational Drugs"
EWING, NJ--(Marketwire - October 09, 2007) - DOR BioPharma, Inc. (OTCBB: DORB) (DOR or the Company) announced that a summary of all clinical trials to date of its drug orBec® (oral beclomethasone dipropionate, or oral BDP) in the treatment of gastrointestinal Graft-versus-Host disease (GI GVHD) has been published in the peer-reviewed medical journal Expert Opinion on Investigational Drugs. The publication "Oral Beclomethasone Dipropionate, a Topically-Active Corticosteroid for Treatment of Gastrointestinal Graft-vs.-Host-Disease Following Allogeneic Hematopoietic Cell Transplantation," is authored by George B. McDonald, MD, inventor of orBec® and Head of the Gastroenterology/Hepatology Section at the Fred Hutchinson Cancer Research Center, located in Seattle, Washington. The full article is available online at http://www.expertopin.com/doi/abs/10.1517/13543784.16.10.1709.
Expert Opinion on Investigational Drugs is a monthly peer-reviewed journal, evaluating developments in pharmaceutical research, from animal studies to the launch of a new medicine. Authors are encouraged to express their Expert Opinion of the status of the research under review, rather than simply review the available data. The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D. Expert Opinion on Investigational Drugs adopts a systematic approach to coverage, with each issue focusing on one of the major therapeutic areas.
The Expert Opinion paper concludes that two randomized, double-blinded placebo-controlled trials have demonstrated that orBec®, formulated as gastric-release and enteric coated pills and dosed at 8 mg/day, is safe and effective in treating acute GI GVHD when used in conjunction with a 10 day induction course of prednisone. In the pivotal Phase 3 trial, among patients eligible for prednisone taper after 10 days of induction therapy, treatment with oral BDP reduces the risk of GVHD treatment failure at study days 50 and 80 by over 60%. The type of pre-transplant conditioning and donor had no impact on the frequency of GVHD treatment failure during the 80-day study period. Both randomized trials demonstrated a 45% reduction in the risk of mortality one year after randomization, due in large part to a reduction in death due to infection and recurrent hematologic malignancy, with the greatest benefit in terms of survival among patients who had received non-myeloablative conditioning therapy and among those who received a graft from other than an HLA-matched sibling. Oral BDP is the only therapy studied in the last 30 years to effectively treat acute GVHD and reduce mortality.
Dr McDonald's opinion is that the use of orBec® in treating the pan-intestinal inflammation of acute GVHD substitutes a well characterized, topically active glucocorticoid with limited systemic bioavailability, less toxicity, and an extensive safety history, for high-dose prednisone, which is a systemic immune suppressant with a multitude of side effects, particularly a predisposition to infections, both opportunistic and routine. The same strategy has been used effectively in treating other inflammatory disorders such as acute attacks of asthma, where an induction course of prednisone to control the acute process is followed by topical, inhaled corticosteroids, including BDP.
"This is the second recent publication of our data in a well regarded peer-reviewed journal," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of DOR BioPharma. "We are pleased with the exposure orBec® has been getting in the medical community as a result of these publications. Two randomized trials have shown that orBec® prevents relapses of acute GI GVHD, with an effect that has been shown to be durable even following discontinuation of therapy. We believe that orBec®, if approved, will potentially provide transplant physicians with an effective and much needed tool to treat their GI GVHD patients and improve outcomes including survival. We will continue working with the FDA and EMEA toward potential regulatory approval".
About the orBec® NDA
The data included in the NDA submission indicate that orBec® may provide clinical benefit when compared with the current standard of care, including a lowered exposure to systemic corticosteroids following allogeneic hematopoietic cell transplant. Currently there are no approved products to treat GI GVHD. Thus an approval of orBec® would represent the first directed therapy for GI GVHD.
The NDA filing is supported by data from two randomized, double-blinded, placebo-controlled clinical trials. The first trial was a 129-patient pivotal Phase 3 multi-center clinical trial of orBec® conducted at 16 leading bone marrow/stem cell transplantation centers in the US and France. The second trial was a 60-patient Phase 2 single-center clinical trial conducted at the Fred Hutchinson Cancer Research Center. Although orBec® did not achieve statistical significance in the primary endpoint of its pivotal trial, namely median time to treatment failure through Day 50 (p-value 0.1177), orBec® did achieve statistical significance in other key secondary endpoints such as the proportion of patients who were treatment failures at study days 50 and 80 and the median time to treatment failure through Day 80 (p-value 0.0226), as well as a 66% reduction in mortality among patients randomized to orBec® at 200 days post-transplant with only 5 patient (8%) deaths in the orBec® group compared to 16 patient (24%) deaths in the placebo group (p-value 0.0139). At one year post-randomization in the pivotal Phase 3 trial, 18 patients (29%) in the orBec® group and 28 patients (42%) in the placebo group died within one year of randomization (46% reduction in mortality, hazard ratio 0.54, 95% CI: 0.30, 0.99, p=0.04, stratified log-rank test).
The frequencies of severe adverse events, adverse events related to study drug, and adverse events resulting in study drug discontinuation were all comparable to that of the placebo group in both trials. Patients who remained on orBec® until Day 50 in the pivotal study had a higher likelihood of having biochemical evidence of abnormal HPA function compared to patients on placebo.
In the Phase 2 study, the primary endpoint was the clinically relevant determination of whether GI GVHD patients at Day 30 were or were not able to consume at least 70% of their daily caloric intake by mouth, as compared to intravenous parenteral nutrition administered in the hospital. The treatment response at Day 30 was 22 of 31 (71%) vs. 12 of 29 (41%) in the orBec® and placebo groups respectively, achieving a statistically significant p-value of 0.02. Additionally, the treatment response at Day 40 was 16 of 31 (52%) vs. 5 of 29 (17%) in the orBec® and placebo groups respectively, achieving a statistically significant p-value of 0.007.
About GI GVHD
GVHD is a debilitating and painful disease. It is a common disorder among immunocompromised cancer patients after receiving allogeneic stem cell or bone marrow transplants. Unlike organ transplantation where the patient's body may reject the organ, in GVHD it is the donor cells that begin to attack the patient's body -- most frequently the gut, liver and skin. Patients with mild-to-moderate GI GVHD typically develop symptoms of anorexia, nausea, vomiting and diarrhea. If left untreated, GI GVHD can progress to ulcerations in the lining of the GI tract, and in its most severe form, can be fatal.
OrBec® is a two-tablet system containing the highly potent, topically active corticosteroid beclomethasone dipropionate, and is designed to specifically target and treat upper and lower GI GVHD with reduced systemic immunosuppressive side effects. Systemic immunosuppressive agents such as prednisone, which are the current standard treatments for GI GVHD, are associated with high mortality rates due to infection and debility. Further, these drugs have not been approved for treating GI GVHD in the European Union or in the US, but rather are used off-label as investigational therapies for this indication.
About Allogeneic HCT
Allogeneic hematopoietic cell transplantation (HCT) is considered a potentially curative option for many leukemias as well as other forms of blood cancer. In an allogeneic HCT procedure, hematopoietic stem cells are harvested from a closely matched relative or unrelated person, and are transplanted into the patient following either high-dose chemotherapy or intense immunosuppressive conditioning therapy. The curative potential of allogeneic HCT is now partly attributed to the so-called graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects of the newly transplanted donor cells to recognize and destroy malignant cells in the recipient patient.
The use of allogeneic HCT has grown substantially over the last decade due to advances in human immunogenetics, the establishment of unrelated donor programs, the use of cord blood as a source of hematopoietic stem cells and the advent of reduced intensity conditioning regimens ("mini-transplants") that avoid the side effects of high-dose chemotherapy. Based on the latest statistics available, it is estimated that there are more than 10,000 HCT procedures annually in the US and a comparable number in Europe. Estimates as to the current annual rate of increase in these procedures are as high as 20%. High rates of morbidity and mortality occur in this patient population. Clinical trials are also underway testing allogeneic HCT for treatment of some metastatic solid tumors such as breast cancer, renal cell carcinoma, melanoma and ovarian cancer. Allogeneic transplants have also been used as curative therapy for several genetic disorders, including immunodeficiency syndromes, inborn errors of metabolism, thalassemia and sickle cell disease. The primary toxicity of allogeneic HCT, however, is GVHD in which the newly transplanted donor cells damage cells in the recipient's gastrointestinal tract, liver and skin.
About orBec®
OrBec® represents a first-of-its-kind oral, locally acting therapy tailored to treat the gastrointestinal manifestation of GVHD, the organ system where GVHD is most frequently encountered and highly problematic. OrBec®, if approved by the EMEA and the FDA, would be the first oral formulation of beclomethasone dipropionate ("BDP") available in the European Union and the United States, respectively. OrBec® is intended to reduce the need for systemic immunosuppressive drugs to treat GI GVHD. BDP is a highly potent, topically active corticosteroid that has a local effect on inflamed tissue. BDP has been marketed in the U.S. and worldwide since the early 1970's as the active pharmaceutical ingredient in a nasal spray and in a metered-dose inhaler for the treatment of patients with allergic rhinitis and asthma. OrBec® is formulated for oral administration as a single product consisting of two tablets; one tablet is intended to release BDP in the proximal portions of the GI tract and the other tablet is intended to release BDP in the more distal portions of the GI tract.
In addition to issued patents and pending worldwide patent applications held by or exclusively licensed to DOR, orBec® also benefits from orphan drug designations in the U.S. and in Europe for the treatment of GI GVHD, which provide for 7 and 10 years of post-approval market exclusivity, respectively.
About DOR BioPharma, Inc.
DOR BioPharma, Inc. (DOR) is a biopharmaceutical company developing products to treat life-threatening side effects of cancer treatments and serious gastrointestinal diseases, and vaccines for certain bioterrorism agents. DOR's lead product, orBec® (oral beclomethasone dipropionate), is a potent, locally acting corticosteroid being developed for the treatment of GI GVHD, a common and potentially life-threatening complication of bone marrow transplantation. DOR has filed an NDA for orBec® with the FDA for the treatment of GI GVHD, and subsequent to supplemental information recently submitted, the FDA has extended the PDUFA (Prescription Drug User Fee Act) date to October 21, 2007. An MAA (Marketing Authorization Application) with the EMEA (European Medicines Evaluation Agency) has also been filed and validated. OrBec® may also have application in treating other gastrointestinal disorders characterized by severe inflammation. DOR has recently initiated a development program with its Lipid Polymer Micelle (LPM™) oral drug delivery technology for the oral delivery of leuprolide for the treatment of prostate cancer and endometriosis, as well as a development program with its oral azathioprine technology for the treatment of oral GVHD.
Through its Biodefense Division, DOR is developing biomedical countermeasures pursuant to the recently enacted Project BioShield Act of 2004. DOR's biodefense products in development are recombinant subunit vaccines designed to protect against the lethal effects of exposure to ricin toxin and botulinum toxin. DOR's ricin toxin vaccine, RiVax™, has been shown to be well tolerated and immunogenic in a Phase 1 clinical trial in normal volunteers.
For further information regarding DOR BioPharma, please visit the Company's website located at www.dorbiopharma.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect DOR BioPharma, Inc.'s current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of orBec® for the treatment of gastrointestinal GVHD and the prospects for regulatory filings for orBec®. Where possible, DOR has tried to identify these forward-looking statements by using words such as "anticipates," "believes," "intends," or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. DOR cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec®, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its technologies will prove to be safe and effective, that its cash expenditures will not exceed projected levels, that it will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the U.S. Government or other countries, that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec® for gastrointestinal GVHD include the risks that: because orBec® did not achieve statistical significance in its primary endpoint in the pivotal Phase 3 clinical study (i.e. a p-value of less than or equal to 0.05), the Oncologic Drug Advisory Committee ("ODAC") appointed by the FDA voted that the data supporting orBec® did not show substantial evidence of efficacy by a margin of 7 to 2 for the treatment of GI GVHD, although the FDA is not bound by ODAC's decision, the FDA may not consider orBec® approvable based upon existing studies, orBec® may not show therapeutic effect or an acceptable safety profile in future clinical trials, if required, or could take a significantly longer time to gain regulatory approval than DOR expects or may never gain approval; DOR is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; or orBec® may not gain market acceptance; and others may develop technologies or products superior to orBec®. These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, DOR's most recent reports on Form 10-QSB and Form 10-KSB. DOR assumes no obligation to update or revise any forward-looking statements as a result of new information, future events, and changes in circumstances or for any other reason.
Company Contact:
Evan Myrianthopoulos
Chief Financial Officer
(609) 538-8200
www.dorbiopharma.com
Cambridge Heart, Inc. (CAMH.OB) – Downgrading to Market Perform -- $155MM Mkt. Cap – (Jason Wittes/Rafael Tejada)
Downgrading to Market Perform as STJ Sales Impact Delayed
â— We are downgrading CAMH to a Market Perform from an Outperform.
â— CAMH pre-reported weak 3Q sales of $2.7 million versus our $4.2 million estimate and consensus of $4.3 million. As such, it no longer expects to make its full year 2007 range of $14-16 million. We estimate that the company sold 33 HearTwave systems in the quarter, versus our projection of 75 systems based on the impact from the STJ partnership.
â— Lack of Visibility Gives Us Pause: While the company believes that nearly 95% of STJ CRM reps have been trained (from 70% in 2Q07), management states that it has taken longer to translate this training into sales than originally anticipated, despite the contractual sales minimums (which have not been disclosed). While we were optimistic about STJ's CRM sales force ability to sell systems, the ramp is slower than expected. This takes away our visibility for this year and for next.
â— Lowering our Estimates: For 4Q07, we are now anticipating $4 million in sales, from our prior $5.8 million estimate. Our full year 2007 sales estimate is now $12 million from our previous $15 million given that CAMH does not anticipate achieving its original 2007 full year guidance of $14-16 million (updated 2007 guidance has not been disclosed). For 2008, we are now expecting $18 million in sales versus our prior $30 million sales estimate.
â— Our revised price valuation approaches $3.00 (from our prior $4.50) based on 5-6x 2012E sales discounted back 3.25 years at a 20% rate, which is our estimated weighted average cost of capital.
View Document
ps: what are you thinking ? do you feel it's a 50-50 or better ?
i am thinking they have a good shot because I saw pazdur at the meeting and he liked the drug. I can't put odds on it.
if his job at the fda is not to kill people, he will see that the drug gets on the market.
I truly believe he knew nothing about the drug until he saw the presentation and that is why the fda briefing docs looked so bad.
we will see soon enough
the 10 day garantee period was not a secondary endpoint so I don't think that is part of any fda analysis.
they didn't have the 10 garantte period as a secondary endpoint because they never expected the failures in the first 10 days. they had a better outcome in the first 10 days in the phase 2 trial.
the only part i think they did a poor job in was that they didn't include the secondary endpoint of treatment failures at 50 days. there were 30 treatment failure on placebo and 18 treatment failures on orbec with a p value of .0515 at day 50.
I think if they had brought that out to the panel members they wouldn't have thought the trial failed. the primary endpoint in the trial was a weighted average of treatment failure though day 50 which had a p value of .11. i think the panel members didn't realize the difference.
the secondary endpoint of .0515 was in the dor briefing docs but i don't think the panel ever even looked at them
because it is standard that when you miss the primary endpoint any other endpoints are hypothesis generating
IMO it was more that the FDA couldn't get behind the primary endpoint failure. Read the two FDA reps response when the question was raised about whether 80 days is just a more mature version of 50 days. They wouldn't answer. They just said there was no alpha left, and there concerns were broad, not just about the 50 day failure. That was the non-objectivity that disappointed me, and IMO was a reflection of the way the agency intended to handle the drug.
the way pazdur wanted them to hand the drug until he saw the data.
remember idmi was in the morning, a bigger market then orbec, he had his hands full turning down provenge, and Amgen epo panel the following day. until he saw the data at the panel meeting he may have known nothing about orbec, and relied on those two jerks
underperform or buy.....I am so confused
Accuray maintained sector underperformer at CIBC (10/05/2007 07:03 ET) Firm is cautious following the company's analyst day in which the firm was not allowed to attend. CIBC highlights the company's failure to differentiate sold units from leased shared ownership units, and believes the ARAY's most recent quarter had the most leased units ever. Firm adds that it is perplexed by the slow rate of Cyberknife installations and that U.S. FY'07 installations were down year/year. Target is lowered by $1 to $15.
Accuray mentioned positively at Jefferies after analyst day (10/05/2007 07:29 ET) Shares are rated buy with a $29 target. The firm cites takeaways frm ARAY's analyst day yesterday. Jefferies says that they are upbeat regarding the expanding SRS market opportunity, potential growth prospects, as well as the favorable reimbursement for SRS and ROI for hospitals that adopt the CyberKnife system.
link to the Q and A part of the Orbec Odac panel
people can read all of the positive statements Pazdur made during the proceedings.
Remember, if he likes the drug and asks for another trial it will never be approved. the fred Hutchinson center supplied 47 percent of the patients. since they use the corn oil they would not be able to do a placebo trial so a new trial would never recruit patients.
http://www.fda.gov/ohrms/dockets/ac/07/transcripts/2007-4301t1-Part4.pdf
see 53208
They both filed under the same parameters (missed primary but extended survival) and the DNDN data was a lot stronger than DORB's data... If you think DORB's case is unusual, and thus unpredictable, then for you DNDN's Provenge should have been a slam dunk approval...
you have a lot to learn if you think Provenge's data is stronger than orbec's
He easily could have just said that they would like to get information out in a public forum and receive feedback from the panel on questions.
he did not have to say the drug has a different impact in his mind irrespective of the panel vote.
if you saw the minutes of the meeting you would also see that these were not his only positive comments.
Richard Pazdur quote after the ODAC panel vote regarding Orbec
"Personally, this drug because of this discussion, irrespective of the vote, has a much different impact in my mind. We will have discussions internally on this drug and discuss the points that were presented here".
what P/R blitz
Dr. Richard Pazdur quote after the negative ODAC panel vote of the drug Orbec
"Personally, this drug because of this discussion, irrespective of the vote, has a much different impact in my mind. We will have discussions internally on this drug and discuss the points that were presented here".
• DOR BioPharma Completes Relocation of Corporate Offices to New Jersey
Marketwire (Tue 7:00am)
• DOR BioPharma Announces Issuance of Patents for Oral Graft Versus Host Disease
Marketwire (Tue, Sep 25)
• orBec(R) Clinical Review Published in "Expert Review of Clinical Immunology"
• DOR BioPharma Announces Initiation of GI Radiation Injury Program Pursuant to $1 Million NIH Grant
Marketwire (Wed, Sep 12)
• DOR BioPharma Announces Publication Describing Protection Against Oral and Aerosol Ricin Exposure With Its Ricin Vaccine RiVax(TM)
Marketwire (Wed, Sep 5)
most small companies without cash raise money, but I see these press releases as being material and not part of a P/R blitz
preliminary data from cxsp t315i registration trial
ChemGenex Announces Positive Preliminary Data from Phase 2/3 Clinical Trial of Ceflatonin ® at International Conference
MELBOURNE, Australia, and MENLO PARK, California U.S.A. (October 1, 2007). ChemGenex
Pharmaceuticals (ASX: CXS, NASDAQ: CXSP) announced today the first presentation of early clinical
data from its registration-directed phase 2/3 clinical study of Ceflatonin ® (omacetaxine mepesuccinate)
at the Fourth ESH International Conference on Chronic Myeloid Leukaemia in Mandelieu, France. The
presentation by Dr Franck Nicolini of the Hôpital Edouard Herriot in Lyon, France described the
growing problem posed by the T315I point mutation in the treatment of chronic myeloid leukemia
(CML) and presented data from four chronic phase T315I positive CML patients who have all benefited
from treatment with Ceflatonin.
Highlights of the presentation entitled “Retrospective Analysis of T315I KD Mutations and Future
Therapeutic Options in CML” include:
• Clinical opinion that CML patients who are confirmed as being T315I positive should be
withdrawn from tyrosine kinase inhibitor (TKI) therapy immediately as ongoing TKI therapy will
increase the likelihood of disease progression.
• Data on four Gleevec ® (imatinib mesylate)-resistant chronic phase, T315I positive CML
patients treated in Lyon by Dr Nicholini and Dr Michallet and in Nice by Dr Legros which
showed hematologic response, disease stabilization and dramatic reductions in the levels of
the T315I mutation in all patients treated. Ceflatonin was generally well tolerated, and no
patients demonstrated unacceptable side-effects.
Dr Nicolini said “I believe that subcutaneous Ceflatonin is today one of the best options to consider for
chronic phase CML patients harbouring a T315I BCR-ABL mutation and lacking a histocompatibility
donor.”
Greg Collier, Ph.D., Chief Executive Officer and Managing Director of ChemGenex said that the
results presented were a strong endorsement of the potential for Ceflatonin to play a significant part in
the therapeutic armoury against CML. “The data that Dr Nicolini presented today show very clearly that
at this early stage we are seeing positive effects in CML patients who, because of the T315I mutation,
are resistant to Gleevec These results support our belief that Ceflatonin has significant clinical
potential for CML patients who become resistant to tyrosine kinase inhibitors and other therapies.”ഊChemGenex Announces Positive Preliminary Data from Phase 2/3 Clinical Trial of Ceflatonin at
International Conference
Page 2 of 3
Ceflatonin ® (omacetaxine mepesuccinate) is a registered trademark of ChemGenex Pharmaceuticals
Limited.
Gleevec ® /Glivec ® is a registered trademark of Novartis AG.
About ChemGenex Pharmaceuticals Limited (www.chemgenex.com)
ChemGenex Pharmaceuticals is a pharmaceutical development company dedicated to improving the
lives of patients by developing therapeutics in the areas of oncology, diabetes and obesity.
ChemGenex harnesses the power of genomics for target discovery and validation, and in clinical trials
to develop more individualized therapeutic outcomes. ChemGenex’s lead compound, Ceflatonin ® , is
currently in phase 2/3 clinical trials for chronic myeloid leukemia (CML) and Quinamed ® is in phase 2
clinical development for prostate, breast and ovarian cancers. The company has a significant portfolio
of anti-cancer, diabetes and obesity programs, several of which have been partnered with international
pharmaceutical companies. ChemGenex currently trades on the Australian Stock Exchange under the
symbol "CXS" and on NASDAQ under the symbol "CXSP".
Contacts
ChemGenex Information
Dr. Greg Collier Dr. Dennis Brown
CEO and Managing Director President and Director
Tel: +61 3 5227 2752 Tel: +1 650 474 9800 ext 108
Cell: +61 (0) 419 897 501 Cell: +1 650 269 1984
Investor Relations
Rebecca Piercy
Buchan Consulting
Tel: +61 2 9237 2800
Email: rpiercy@bcg.com.au
Safe Harbor Statement
Certain statements made herein that use the words “estimate”, “project”, “intend”, “expect”, “believe”
and similar expressions are intended to identify forward-looking statements within the meaning of the
US Private Securities Litigation Reform Act of 1995. These forward-looking statements involve known
and unknown risks and uncertainties which could cause the actual results, performance or
achievements of the company to be materially different from those which may be expressed or implied
by such statements, including, among others, risks or uncertainties associated with the development of
the company’s technology, the ability to successfully market products in the clinical pipeline, the ability
to advance promising therapeutics through clinical trials, the ability to establish our fully integrated
technologies, the ability to enter into additional collaborations and strategic alliances and expand
current collaborations and obtain milestone payments, the suitability of internally discovered genes for
drug development, the ability of the company to meet its financial requirements, the ability of the
PO Box 1069, Grovedale Victoria 3216, Australia Telephone: +61 3 5227 2752 Facsimile: +61 3 5227 1322
Email: chemgenex@chemgenex.com ABN 79 000 248 304ഊChemGenex Announces Positive Preliminary Data from Phase 2/3 Clinical Trial of Ceflatonin at
International Conference
Page 3 of 3
company to protect its proprietary technology, potential limitations on the company’s technology, the
market for the company’s products, government regulation in Australia and the United States, changes
in tax and other laws, changes in competition and the loss of key personnel. These statements are
based on our management’s current expectations and are subject to a number of uncertainties that
could change the results described in the forward-looking statements. Investors should be aware that
there are no assurances that results will not differ from those projected.
PO Box 1069, Grovedale Victoria 3216, Australia Telephone: +61 3 5227 2752 Facsimile: +61 3 5227 1322
Email: chemgenex@chemgenex.com ABN 79 000 248 304
ENDP This is a classic: Sunday morning announcement
the important fact is not the timing of the announcement. I am sure the companies met with the FDA to discuss the appropriate endpoint for a phase 3 trial. This is Endo Pharmaceuticals not some fly by night operation looking for headlines. The FDA now states the endpoints they met weren't clinically meaningful, this should have been part of the discussion during the end of phase 2 meetings. The FDA is also asking them to prove a negative. They haven't seen any serious vascular adverse events but that doesn't mean there won't be any in the future. How do you deal with that. This is not going to be a drug that will be used every day. It is only going to be used a few days a month to prevent a migraine. The drug is already approved.
I see this as a significant raising of the bar. Watch out obesity drugs.
While the FDA acknowledged that both pivotal efficacy trials that had been submitted as part of this sNDA met their primary endpoints in significantly improving the number of headache-free perimenstrual periods (PMPs), it questioned whether the benefit demonstrated was clinically meaningful. The FDA also noted that even though serious vascular adverse events were not observed in this drug development program, an increased risk (compared to the approved acute use) could not be ruled out.
Pipelines Key in Biotech Investments
With Grant Zeng
Aug 23, 2007
We had many questions for Zacks senior biotechnology industry analyst Grant Zeng, CFA regarding not only which companies in his coverage should outperform the market, but how much recent stock market fluctuations have affected the industry.
What specific Buy recommendations in biotech do you currently have?
I have quite a few Buy recommendations under my coverage. These names include), Critical Therapeutics (CRTX).
Can you give us some details about these companies?
Another company is Critical Therapeutics, Inc. Critical is a small biopharmaceutical company focused on the discovery, development, and commercialization of products for respiratory, inflammatory, and critical care diseases. The company has two products, Zyflo and Zyflo CR for asthma, on the market.
Another reason I am optimistic about Zyflo CR is that the company has a strong promotion partner Dey LP. Dey LP is a recognized leader in respiratory care and has track record of performance in this area. The co-promotion agreement leverages the expertise of both companies in the U.S. respiratory market. The combined sales force of 240 sales reps should generate greater physician and patient awareness of the therapeutic benefits of Zyflo CR going forward.
The asthma market is huge but also competitive. Zyflo faces tough competition from big players like Singular from Merck (MRK) and Advair from GlaxoSmithKline (GSK). However, I believe Zyflo could carve a niche by differentiation. Zyflo is being promoted as a treatment for patients with moderate-to-severe asthma. This market consists of more than five million patients and presents a significant opportunity for Zyflo. Peak sales for Zyflo CR should be around $500 million. Bottom line, Critical Therapeutics is on track to achieve profitability in 2009.
Critical Therapeutics and Dey Launch Twice-Daily ZYFLO CR(TM) (Zileuton) Extended-Release Tablets
Thursday September 27, 8:00 am ET
the company has an entperprise value of about 35 million dollars
240-person Sales Force Begins Rollout to 18,000 Respiratory Specialists and Primary Care Physicians Throughout the U.S.
LEXINGTON, Mass.--(BUSINESS WIRE)--Critical Therapeutics, Inc. (Nasdaq: CRTX - News) and Dey, L.P. (DEY), today began the nationwide launch of ZYFLO CR(TM) (zileuton) extended-release tablets, a twice-daily medication for the prevention and chronic treatment of asthma in patients 12 years of age and older. With a combined 240-person U.S. sales force, Critical Therapeutics and DEY have begun promoting ZYFLO CR to a targeted group of approximately 18,000 allergists, pulmonologists and primary care physicians throughout the United States.
Source: Critical Therapeutics, Inc.
"We are excited that we are now able to offer doctors and their patients a twice-daily dosing regimen with a similar safety profile as ZYFLO® (zileuton tablets), our four-times-daily immediate-release formulation," said Frank Thomas, president and chief executive officer of Critical Therapeutics. "While asthma prevalence continues to rise, we are pleased that we can offer an asthma treatment with a unique mechanism of action. ZYFLO and ZYFLO CR are the only leukotriene synthesis inhibitors approved by the U.S. Food and Drug Administration (FDA). ZYFLO has already helped many patients better control their asthma symptoms and we look forward to seeing those positive outcomes continue as we bring ZYFLO CR to market."
The 2007 Guidelines for the Diagnosis and Management of Asthma, which were developed by the National Asthma Education and Prevention Program (NAEPP), recommend zileuton as a therapeutic alternative for patients as part of a step-approach to reducing asthma symptoms and preventing exacerbations. It is the first time zileuton has been separately recognized in the guidelines since the NAEPP was initiated in 1989.
"The potential benefit of zileuton to help control a patient's asthma is supported by its inclusion in the new NAEPP guidelines," Thomas said. "We expect the guidelines to help raise the profile of ZYFLO CR as a treatment option for the many patients whose symptoms are still uncontrolled, despite the current therapies they are taking."
"Asthma impacts millions of patients in a debilitating cycle of sleep disruption, interference with physical activity, absenteeism from work and school and frequent trips to the doctor's office," said Allan T. Luskin, M.D., associate professor of medicine at the University of Wisconsin. "As a novel leukotriene synthesis inhibitor, ZYFLO CR has the potential to help asthma patients improve their disease."
ZYFLO CR and ZYFLO are the only FDA-approved leukotriene synthesis inhibitors for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. ZYFLO CR and ZYFLO are not indicated for use in the reversal of bronchospasm in acute asthma attacks, but can be continued during acute exacerbations of asthma. Leukotrienes are inflammatory mediators in asthma that can trigger asthma symptoms, including inflammation, swelling, bronchoconstriction and mucus secretion. ZYFLO CR uses SkyePharma PLC's (LSE: SKP - News) proprietary Geomatrix® drug delivery technology, which controls the amount and rate of drug released into the body.
Pricing Information
ZYFLO CR will be priced at a wholesale acquisition cost (WAC) of $244.00 per month. The drug will be supplied to pharmacies in bottles of 120 tablets, representing a one-month supply for an individual patient.
About Asthma
Asthma is a chronic inflammatory disorder affecting approximately 20 million Americans. Asthma occurs when the walls of the bronchial tubes become inflamed, causing the muscles to constrict and extra mucus to be produced. This can lead to a broad range of symptoms from minor wheezing to severe difficulty in breathing. In some cases, breathing becomes so difficult during a flare-up or "asthma attack" that symptoms can be life threatening if not properly managed.
About ZYFLO CR and ZYFLO
ZYFLO CR and ZYFLO are the only FDA-approved leukotriene synthesis inhibitors for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. ZYFLO CR and ZYFLO are not indicated for use in the reversal of bronchospasm in acute asthma attacks. Therapy with ZYFLO CR and ZYFLO can be continued during acute exacerbations of asthma.
The recommended dose of ZYFLO CR is two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals, for a total daily dose of 2400 mg. The recommended dose of ZYFLO is one 600 mg immediate-release tablet four times a day for a total daily dose of 2400 mg.
ZYFLO CR and ZYFLO are contraindicated in patients with active liver disease or transaminase elevations greater than or equal to three times the upper limit of normal. A small percentage of patients treated with ZYFLO CR (2.5%) and ZYFLO (1.9%) in placebo-controlled trials showed an increased release of a liver enzyme known as ALT and bilirubin (an orange or yellowish pigment in bile). As a result, the level of liver enzymes in patients treated with ZYFLO CR and ZYFLO should be measured by a simple blood test. It is recommended that physicians perform this test before administering ZYFLO CR and ZYFLO and repeat the test on a regular basis while patients are on the medication. Patients taking ZYFLO CR and theophylline should reduce the theophylline dose by 50%. Patients taking ZYFLO CR and propranolol or warfarin should be monitored and doses adjusted as appropriate. Most common side effects associated with the use of ZYFLO CR and ZYFLO are sinusitis, nausea and pharyngolaryngeal pain and abdominal pain, upset stomach and nausea, respectively.
For full prescribing information for ZYFLO CR, please visit www.zyflocr.com or call the Company's toll free telephone number 1-866-835-8216 to request medical information.
For full prescribing information for ZYFLO, please visit www.zyflo.com or call the Company's toll free telephone number 1-866-835-8216 to request medical information.
About Critical Therapeutics
Critical Therapeutics, Inc. is developing and commercializing innovative products for respiratory, inflammatory and critical care diseases. The Company owns worldwide rights to two FDA-approved drugs for the prevention and chronic treatment of asthma in patients 12 years of age and older: twice-daily ZYFLO CR(TM) (zileuton) extended-release tablets and ZYFLO® (zileuton tablets). Critical Therapeutics is working to develop products for acute asthma attacks that lead patients to the emergency room and other urgent care settings. The Company also is developing therapies directed toward the body's inflammatory response. Critical Therapeutics is located in Lexington, Mass. For more information, please visit www.crtx.com.
Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for Critical Therapeutics, Inc., including, without limitation, statements regarding our commercial launch of ZYFLO CR, possible therapeutic benefits, market acceptance and future sales of ZYFLO CR and ZYFLO, the anticipated success of our co-promotion arrangements with DEY, our strategy, future operations, financial position, future revenues and projected costs, prospects, plans and objectives of management, and all other statements that are not purely historical in nature, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "plan," "project," "should," "will," "would" and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties relating to: our ability to successfully market and sell ZYFLO CR and ZYFLO, including the success of our co-promotion arrangement with DEY; our ability to develop and maintain the necessary sales, marketing, distribution and manufacturing capabilities to commercialize ZYFLO CR and ZYFLO; patient, physician and third-party payor acceptance of ZYFLO CR and ZYFLO as safe and effective therapeutic products; adverse side effects experienced by patients taking ZYFLO CR or ZYFLO; our heavy dependence on the commercial success of ZYFLO CR; our ability to maintain regulatory approvals to market and sell ZYFLO CR and ZYFLO; our ability to successfully enter into additional strategic co-promotion, collaboration or licensing transactions on favorable terms, if at all; conducting clinical trials, including difficulties or delays in the completion of patient enrollment, data collection or data analysis; the results of preclinical studies and clinical trials with respect to our products under development and whether such results will be indicative of results obtained in later clinical trials; our ability to obtain the substantial additional funding required to conduct our research, development and commercialization activities; our dependence on our strategic collaboration with MedImmune, Inc.; and our ability to obtain, maintain and enforce patent and other intellectual property protection for ZYFLO CR and ZYFLO, our discoveries and our drug candidates. These and other risks are described in greater detail in the "Risk Factors" section of our most recent Quarterly Report on Form 10-Q and other filings that we make with the Securities and Exchange Commission. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements.
In addition, the statements in this press release reflect our expectations and beliefs as of the date of this release. We anticipate that subsequent events and developments will cause our expectations and beliefs to change. However, while we may elect to update these forward-looking statements publicly at some point in the future, we specifically disclaim any obligation to do so, whether as a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this release.
ZYFLO® is a registered trademark of Critical Therapeutics, Inc.
ZYFLO CR(TM) is a trademark of Critical Therapeutics, Inc.
GEOMATRIX® is a registered trademark of SkyePharma PLC.
MULTIMEDIA AVAILABLE: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=5503492
Contact:
Critical Therapeutics, Inc.
Linda S. Lennox, 781-402-5708
Vice President, Investor & Media Relations
llennox@crtx.com
Critical Therapeutics Highlights Near-Term Milestones to Drive Commercial Success and Clinical Development
company is launching their twice a day zyflo called zyflo cr
They had an analyst day today. listen to the webcast.
Tuesday September 25, 4:00 pm ET
At 2007 Analyst Day, Company Discusses ZYFLO CR(TM) Launch Strategy, R&D Programs and Provides Guidance on Key Financial Metrics
LEXINGTON, Mass.--(BUSINESS WIRE)--Critical Therapeutics, Inc. (Nasdaq: CRTX - News) today hosted its 2007 Analyst Day at the Four Seasons Hotel in New York. During the event, the Company:
1. announced its September 27, 2007 U.S. launch date for ZYFLO CR(TM) (zileuton) extended-release tablets;
2. updated analysts and investors on its ZYFLO CR launch strategy and co-promotion partnership with Dey, L.P. (DEY);
3. reviewed the Company's three clinical development programs and its two novel drug candidates in preclinical development programs; and
4. provided certain operational and financial guidance for 2007.
"We have several near-term milestones on the horizon, including the launch of two new products that position us for success and provide the momentum to drive long-term value for shareholders," Frank Thomas, president and chief executive officer of Critical Therapeutics, told Analyst Day attendees.
On September 27, 2007, Critical Therapeutics and its co-promotion partner, DEY, will commercially launch ZYFLO CR in the U.S. The companies expect to follow the launch of ZYLFO CR with the upcoming launch later this fall of Perforomist(TM) (formoterol fumurate) Inhalation Solution, DEY's new treatment for chronic obstructive pulmonary disease (COPD).
"We are complementing the commercial launch of these products with zileuton-associated clinical development programs and earlier product development programs centered on controlling the production of potent inflammatory mediators that play a key role in regulating the body's immune system," Thomas said. "We are excited about the progress we are making in our clinical development of an injectable formulation of zileuton for adjunctive use in acute asthma exacerbations and the development of a new oral formulation through our R(+) zileuton isomer program."
The Analyst Day featured a panel session with three expert respiratory physicians:
Allan T. Luskin, M.D., Clinical Associate Professor of Medicine, University of Wisconsin; Director of Respiratory Institute, Dean Medical Center, Madison, Wisconsin, addressed the prevalence of asthma, which continues to grow at a rapid pace. Dr. Luskin highlighted the inclusion of zileuton in new guidelines from the National Asthma Education and Prevention Program (NAEPP). "At least one-third of asthma patients' medications do not provide them with the necessary relief from their symptoms," said Dr. Luskin. "The new NAEPP guidelines, which now recommend zileuton as a therapeutic alternative, will be widely distributed amongst leading respiratory specialists and will incorporate new treatment options, which may improve clinical control for asthma patients."
Bradley E. Chipps, M.D., Medical Director of Respiratory Therapy and the Cystic Fibrosis Center, Sutter Medical Center; Capital Allergy and Respiratory Disease Center, Sacramento, California, discussed the importance of ZYFLO CR as a new treatment option for asthma patients. "This new treatment provides another therapeutic option for patients whose asthma symptoms are still uncontrolled despite their current therapies," he said.
Philip Marcus, M.D., MPH, Chief, Division of Pulmonary and Critical Care Medicine, St. Francis Hospital, Roslyn, NY; Clinical Professor of Medicine and Pharmacology, New York College of Osteopathic Medicine, described his personal experience with a patient whose symptoms improved after four months on ZYFLO. "The patient is eagerly awaiting the launch of ZYFLO CR," Dr. Marcus said.
ZYFLO CR Launch
ZYFLO CR will be commercially launched nationwide on Thursday, September 27, 2007, with a combined sales force of 240 sales representatives calling on more than 18,000 allergists, pulmonologists and primary care physicians. Roger Heerman, vice president of sales and marketing, told the investment community, "We are excited to offer a twice-daily dosing regimen of ZYFLO CR for patients. In addition to a large and experienced specialty-focused sales team, ZYFLO CR will be supported by new branding designed to highlight the drug's unique mechanism of action."
R&D Pipeline
Trevor Phillips, chief operating officer, provided attendees with an overview of the Company's clinical programs and pre-clinical pipeline. "In the coming weeks, we will have three clinical trials underway and two compounds in late pre-clinical development. We believe these programs have the potential to achieve important milestones for investors over the next 12 to 18 months."
Highlights from these programs include:
Phase IV trial of ZYFLO CR in asthma patients on inhaled corticosteroids. Results from this trial are expected to be available in late 2008;
Phase I trial of R(+) zileuton isomer. Results from this trial are expected in the first quarter of 2008;
Phase II trial of zileuton injection for adjunctive use in acute exacerbations of asthma. Results from this trial are expected in the third quarter of 2008;
Alpha-7 agonist program. A lead compound has been selected for further development. The Company expects to conduct toxicology studies on this compound in the first half of 2008 and submit an Investigational New Drug Application with the U.S. Food and Drug Administration (FDA) in the second half of 2008; and
HMGB1 Antibody. In collaboration with MedImmune, Inc., the selection of a clinical candidate is expected by early 2008.
Financial Guidance
Tucker Kelly, chief financial officer and senior vice president of finance and corporate development, reviewed the terms of the Company's co-promotion agreement with DEY and reiterated full year 2007 net cash expenditure guidance of between $23 million and $25 million.
Presentation slides from the event are available in the Analyst Day section of the Company's Investor Relations website at www.crtx.com.
About Critical Therapeutics
Critical Therapeutics, Inc. is developing and commercializing innovative products for respiratory, inflammatory and critical care diseases. The Company owns worldwide rights to two FDA-approved drugs for the prevention and chronic treatment of asthma in patients 12 years of age and older: twice-daily ZYFLO CR(TM) (zileuton) extended-release tablets and ZYFLO® (zileuton tablets). Critical Therapeutics is working to develop products for adjunctive use in acute asthma attacks that lead patients to the emergency room and other urgent care settings. The Company also is developing therapies directed toward the body's inflammatory response. Critical Therapeutics is located in Lexington, Mass. For more information, please visit www.crtx.com.
About ZYFLO and ZYFLO CR
ZYFLO CR(TM) and ZYFLO® (zileuton tablets) are the only FDA-approved leukotriene synthesis inhibitors for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. ZYFLO CR and ZYFLO are not indicated for use in the reversal of bronchospasm in acute asthma attacks, but can be continued during acute exacerbations of asthma. Leukotrienes are inflammatory mediators in asthma that can trigger asthma symptoms, including inflammation, swelling, bronchoconstriction and mucus secretion.
The recommended dose of ZYFLO CR is two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals, for a total daily dose of 2400 mg. The recommended dose of ZYFLO is one 600 mg immediate-release tablet four times a day for a total daily dose of 2400 mg.
ZYFLO CR and ZYFLO are contraindicated in patients with active liver disease or transaminase elevations greater than or equal to three times the upper limit of normal. A small percentage of patients treated with ZYFLO CR (2.5%) and ZYFLO (1.9%) in placebo-controlled trials showed an increased release of a liver enzyme known as ALT and bilirubin (an orange or yellowish pigment in bile). As a result, the level of liver enzymes in patients treated with ZYFLO CR and ZYFLO should be measured by a simple blood test. It is recommended that physicians perform this test before administering ZYFLO CR and ZYFLO and repeat the test on a regular basis while patients are on the medication. Patients taking ZYFLO CR and theophylline should reduce the theophylline dose by 50%. Patients taking ZYFLO CR and propranolol or warfarin should be monitored and doses adjusted as appropriate. Most common side effects associated with the use of ZYFLO CR and ZYFLO are sinusitis, nausea and pharyngolaryngeal pain and abdominal pain, upset stomach and nausea, respectively.
For full prescribing information for ZYFLO CR, please visit www.zyflocr.com or call the Company's toll free telephone number at 1-866-835-8216 to request medical information.
For full prescribing information for ZYFLO, please visit www.zyflo.com or call the Company's toll free telephone number at 1-866-835-8216 to request medical information.
About Perforomist
Perforomist(TM) Inhalation Solution is indicated for the long-term, twice- daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema.
Important Safety Information
Perforomist(TM) belongs to a class of medications known as long-acting beta(2)-adrenergic agonists (LABAs). LABAs may increase the risk of asthma-related death. Data from a large placebo-controlled US study comparing the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to formoterol (a LABA), the active ingredient in Perforomist(TM).
Perforomist(TM) should not be used in patients with acutely deteriorating COPD or to treat acute symptoms. Acute symptoms should be treated with fast-acting rescue inhalers. Perforomist(TM) should not be used with other medications containing LABAs. Do not use more than one nebule twice daily. Perforomist(TM) should be used with caution in patients with cardiovascular disorders. Perforomist(TM) is not a substitute for inhaled or oral corticosteroids. The safety and efficacy of Perforomist(TM) in asthma has not been established. In COPD clinical trials, the most common adverse events reported with Perforomist(TM) were diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia
Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for Critical Therapeutics, Inc., including, without limitation, statements regarding our commercial launch of ZYFLO CR, possible therapeutic benefits, market acceptance and future sales of ZYFLO CR and ZYFLO, the anticipated success of our co-promotion arrangements with DEY, the anticipated commercial launch of Perforomist, the progress and timing of our drug development programs and related trials, the efficacy of our drug candidates, our strategy, future operations, financial position, future revenues and projected costs, including our net cash expenditures for 2007, prospects, plans and objectives of management, and all other statements that are not purely historical in nature, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "plan," "project," "should," "will," "would" and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties relating to: our ability to successfully market and sell ZYFLO CR and ZYFLO, including the success of our co-promotion arrangement with DEY; our ability to develop and maintain the necessary sales, marketing, distribution and manufacturing capabilities to commercialize ZYFLO CR and ZYFLO; patient, physician and third-party payor acceptance of ZYFLO CR and ZYFLO as safe and effective therapeutic products; adverse side effects experienced by patients taking ZYFLO CR or ZYFLO; our heavy dependence on the commercial success of ZYFLO CR; our ability to maintain regulatory approvals to market and sell ZYFLO CR and ZYFLO; our ability to successfully enter into additional strategic co-promotion, collaboration or licensing transactions on favorable terms, if at all; conducting clinical trials, including difficulties or delays in the completion of patient enrollment, data collection or data analysis; the results of preclinical studies and clinical trials with respect to our products under development and whether such results will be indicative of results obtained in later clinical trials; our ability to obtain the substantial additional funding required to conduct our research, development and commercialization activities; our dependence on our strategic collaboration with MedImmune, Inc.; and our ability to obtain, maintain and enforce patent and other intellectual property protection for ZYFLO CR and ZYFLO, our discoveries and our drug candidates. These and other risks are described in greater detail in the "Risk Factors" section of our most recent Quarterly Report on Form 10-Q and other filings that we make with the Securities and Exchange Commission. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements.
In addition, the statements in this press release reflect our expectations and beliefs as of the date of this release. We anticipate that subsequent events and developments will cause our expectations and beliefs to change. However, while we may elect to update these forward-looking statements publicly at some point in the future, we specifically disclaim any obligation to do so, whether as a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this release.
ZYFLO® is a registered trademark of Critical Therapeutics, Inc.
ZYFLO CR(TM) is a trademark of Critical Therapeutics, Inc.
Perforomist(TM) is a trademark of Dey, L.P.
Contact:
Critical Therapeutics, Inc.
Linda S. Lennox, 781-402-5708
Vice President, Investor & Media Relations
llennox@crtx.com
--------------------------------------------------------------------------------
Source: Critical Therapeutics, Inc.
You do know that in addition to writing about biotech companies for several years for TheStreet.com, he also worked at a hedge fund as a biotech analyst for a couple years ... right?
evidently he wasn't too successful at it because he is back at the street.com getting his stories from hedgies that want to get out of positions.
I wouldn't put him in the top one percent. because he doesn't do any work of his own. he regurgitates.
that is what a bird does when feeding its young
Adam Feuerstein
Senior Writer
Email
--------------------------------------------------------------------------------
Before joining TheStreet.com in March 2001, Feuerstein covered business software for Upside.com. Prior to that he covered a variety of business beats, including technology and commercial real estate, at the San Francisco Business Times.
Feuerstein graduated from Emory University with a bachelor's degree in political science.
It seems that the reason no one on the board is too impressed by Feursetein's analysis is because the contributors on this board probably are more qualified to write about biotech than he is. I believe his analysis is generated by hedge funds feeding him stories.
panacea pharmaceuticals. has anyone looked into it or is it a scam.
It seems that if someone has a high psa but a low level of the protein haah it would reduce a large number of biopsies, it what they are saying is true. Could they get the clia waiver without some kind of data
http://www.panaceapharma.com/press/05_31_2007.htm
http://www.panaceapharma.com/press/07_17_2007.htm
sonus from fuerstein
he felt better about the drug's chances before the stock got weak. he sounds more like a message board contributer than a professional analyst.
From reader BG: "Regarding Sonus Pharmaceuticals, there have been several drops in the stock price the past month or two on relatively increased volume. In the biotech space, should investors ever associate this type of movement with leaked data, or is that more a chat room myth?"
I share BG's worries about Sonus. The stock started to show some signs of life at the end of the August, getting above $4, but still, a stronger stock price at this point would be nice to bolster my confidence about the upcoming release of all-important phase III data on Sonus' breast cancer drug Tocosol paclitaxel. (You can read my take on the drug and this trial here.)
BG asks a good question: Does someone on the Street know something about the Sonus clinical trial, which would explain the stock's weakness? The short answer is that I don't know. I haven't heard any leaks about the Tocosol paclitaxel data yet, although that certainly doesn't mean they don't exist.
Let's be realistic, professional biotech investors often go to great lengths to get an edge on big stock-moving events like phase III trial results. I don't mean to imply they resort to illegalities (although I have witnessed ethical lines being crossed), but let's just say it shouldn't surprise anyone that a biotech hedge fund manager, for instance, will have a leg up on the rest of us when it comes to anticipating or predicting phase III data.
Now, in Sonus' case, the company has already announced that the Tocosol paclitaxel study is done and the data are being analyzed, with results expected soon. This does raise concerns about data leakage -- it can't be ruled out.
But before we get all conspiratorial, let's not forget that there are legitimate risks to this Tocosol paclitaxel clinical trial. Positive results were never a sure thing. Couple that with a seemingly lukewarm relationship between Sonus and its big corporate partner Bayer (BAY) , and that may be all you need to keep the stock price depressed.
at the end of 3 months do you anticipate not having to take the drug
Dorb excerpts of ODAC transcript
since there seems to be some interest I figured this was worth posting again
Dr. Pazdur asks the panel to discuss whether another trial is feasible to run
1 large treatment, single-arm trial.
2 Here again, one of the questions that I have,
3 if that would be ongoing, would people even consider
4 doing another trial? Would another trial be feasible to
5 do? That’s another issue.
6 CHAIRPERSON HUSSAIN: Is this an issue you
7 want us to discuss now, or this is an issue that we want
8 to discuss after the vote?
9 DR. PAZDUR: Probably after the vote or it can
10 be discussed during the vote.
11 (General laughter.)
12 DR. PAZDUR: It’s really going to be part and
13 parcel of a decision here.
14 CHAIRPERSON HUSSAIN: Yes. Just a point of
15 clarification. If someone gets an IND for a specific
16 treatment, who pays for the cost of the drug?
17 DR. PAZDUR: Usually, the Sponsor would assume
18 the cost of that. Under the treatment IND mechanism,
19 however, which is a special type of expanded access
20 program, there can be some cost recovery on the part of
21 the Sponsor. We would entertain in a situation such as
22 this that type of program.
Mcdonal explains why trials using the drug for acute gvhd would be hard to run, because the doctors are formulating a drug themselves that isn't as good as Orbec but is better than placebo
1 in this group of patients for ethical and practical
2 reasons.
3 CHAIRPERSON HUSSAIN: Could you not consider
4 doing a trial, not placebo-controlled but with
5 equivalent doses of steroids to make the point that your
6 agent has a superior profile with regard to infections,
7 complications of steroids, and things of that sort? It
8 doesn’t have to be necessarily a survival-driven trial
9 but an efficacy trial?
10 DR. McDONALD: I think that is a
11 consideration, but actually there are some data that
12 bears on the question. If you look at the placebo arm
13 of 875, you will discover that 41 percent of people
14 required only 10 days of prednisone. If you look at the
15 placebo arm of the pivotal trial, 55 percent required
16 only 10 days of prednisone.
17 I think it is very difficult to argue that a
18 high-dose prednisone regiment would benefit any of those
19 patients who required only 10 days of prednisone. I
20 think the same ethical issues exist in doing a very
21 high-dose prednisone versus this approach.
22 We have already proved, I think, that the
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1 minimum prednisone approach protected by BDP has far
2 superior results to our 25-year standard of care. Again,
3 it is not the GVH that is killing people; it is the
4 treatment for GVH that’s doing the job.
5 I think we have adequately proved that BDP has
6 a steroid-sparing effect. I’m not sure I can go back 25
7 years in time and grab our old regimens. I am quite
8 convinced. I think it might well be unethical to do
9 that kind of a comparison.
10 DR. RODELL: Excuse me. Dr. Sullivan from
11 Duke was actually not involved in the trial.
12 CHAIRPERSON HUSSAIN: I just have another
13 question, though, please. If you say you don’t want to
14 go back to the past and grab old regimens, and if your
15 drug is currently not available on the market, and we
16 have heard that people use the oil-mixed product with
17 something, is that what people are currently using? Is
18 that what the alternative out there is?
19 DR. McDONALD: The alternative is what I call
20 the ad-hoc way of formulating something that is similar
21 to what we are using in these trials, that is, to use
22 the corn oil combined with budesonide.
the panel votes no
1 overwhelmingly we were against something and the FDA
2 approved it anyway.
3 (General laughter.)
4 CHAIRPERSON HUSSAIN: They don’t necessarily
5 always listen to us. Thank you.
6 If there are no other burning questions or
7 comments, I’m going to try to ask that we go ahead to
8 the vote.
9 Put the question up again, please.
10 (Staff complies.)
11 CHAIRPERSON HUSSAIN: We will begin around the
12 table. No description of why one is voting yes or no,
13 just the vote yes or no. Identify please yourself and
14 speak clearly into the microphone.
15 Dr. Link, can we begin with you, please?
16 DR. LINK: Michael Link. I vote no that it
17 has not shown substantial evidence.
18 MS. HAYLOCK: Haylock, no.
19 DR. HARRINGTON: No.
20 DR. MORTIMER: Mortimer, no.
21 CHAIRPERSON HUSSAIN: Hussain, no.
22 DR. RICHARDSON: Richardson, no.
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1 DR. PERRY: Perry, no.
2 DR. SPORTES: Sportes, yes.
3 DR. FLATAU: Flatau, yes.
4 CHAIRPERSON HUSSAIN: Two yes, seven no.
5 Dr. Pazdur, do you want us to go into the
6 second issue of design, of study design?
7 DR. PAZDUR: We’ve already started the
8 discussion.
9 CHAIRPERSON HUSSAIN: Yes, but I thought it
10 was for discussion, not for a vote.
11 DR. PAZDUR: We’ve already started the
12 discussion.
13 CHAIRPERSON HUSSAIN: In terms of what ideal
14 study design is?
15 DR. PAZDUR: Yes.
16 CHAIRPERSON HUSSAIN: Maybe I can begin and
17 ask the sponsor first, when you look at your data and
18 you look at what you started with and then what you got,
19 what do you think, like in your gut with yourself
20 looking at this, where do you think your strongest point
21 was? Because that seems to me where you should then go
22 back to look at that area because that may be where
Hussein explains that you couldn't run a trial in this population that could be stratified equally.
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1 between treatment arms, it would require, roughly, 160
2 deaths and a true hazard ratio of 0.55 would require,
3 roughly, 120 deaths. The accrual would be quite
4 substantial.
5 CHAIRPERSON HUSSAIN: Any words of wisdom from
6 committee members as far as study designs or suggestions
7 to the Sponsor or to the FDA with regard to what they
8 should advise them to do?
9 Sir?
10 DR. FLATAU: Yes. I would like to think at
11 least a secondary endpoint of overall survival at least
12 at one year, if not longer, would be interesting.
13 CHAIRPERSON HUSSAIN: I guess the only concern
14 I have about survival is unless you make the population
15 entering very uniform with the same diseases, the same
16 regimen, the same everything, you are never going to be
17 able to interpret the results, it would seem to me,
18 unless you stratify very clear where you include several
19 groups of people clearly stratified equal in each arm.
20 I can’t see how you would do it if you argue that we
21 don’t have a huge population.
Dr. Sportes the only transplant doctor on the panel and one of the positive votes explained that the 80 day endpoint which was met clinically means more than the 50 day endpoint
22 DR. SPORTES: Actually, I was wondering and I
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1 should have asked earlier why the secondary endpoint was
2 not the primary endpoint.
3 It seems to me from a transplant perspective
4 that a followup at 80 days is probably the strongest
5 endpoint, which is why I voted yes is because I think to
6 me conceptually this is much more a reflection of the
7 entire intervention. Why was that not chosen? I just
8 seek some explanation.
9 DR. RODELL: May I respond to that?
10 CHAIRPERSON HUSSAIN: Yes.
11 DR. RODELL: I think it’s important to
12 recognize the history of how this drug was developed.
13 The initial study, the initial efficacy study was Study
14 875 that was done essentially on a completely open
15 field, that is, this type of study had never been done
16 before and so the 30-day endpoint was selected in that
17 study, essentially, arbitrarily.
18 Once the results of that study were know, Dr.
19 McDonald spoke with and talked to the FDA, shared with
20 them the results of that study and began to design the
21 02 Study.
22 The two components with respect to efficacy
Dr. Link explains that the first 10 days on Orbec should be a guarantee period and is surprised that they didn't show this slide before the vote.
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1 The practicality, even without getting into
2 the economics of doing another study, is going to be a
3 significant issue in terms of the future development of
4 the drug.
5 CHAIRPERSON HUSSAIN: Thank you.
6 Any other comments?
7 (No verbal response.)
8 CHAIRPERSON HUSSAIN: Well, we will begin with
9 Dr. Link, then, and we will go around the table.
10 DR. LINK: I have two. The first is a
11 question of what if you actually -- the mistake maybe
12 was that you started the clock too soon in terms of you
13 started on the day of randomization. Either if you if
14 you had randomized after the 10 days and only randomized
15 responders -- Dave, you’re not going to shoot me here,
16 are you?
17 The second things is to actually do an
18 analysis, start the clock when they achieve remission
19 and throw out people who didn’t achieve remission, which
20 is often done in transplant studies. That would be one
21 suggestion.
22 What does it look like? Does it look better?
1 Does it look like you had achieved your goal, just out
2 of curiosity?
3 DR. RODELL: Yes, let me ask Mr. Cruickshank
4 to address that.
5 (PowerPoint presentation is in progress.)
6 MR. CRUICKSHANK: Going back to that question
7 about, what is the effect of those early failures, we
8 did do an analysis to look at the effect whereby
9 patients who failed during the 10-day high-dose
10 induction period of prednisone.
11 If you sensor the patients at the time of
12 treatment failure, you can see here that we lose the
13 effect of the crossing Kaplan-Meier curves. We have a
14 fairly clear, sustained difference between the arms at
15 day 50 as well as day 80.
16 DR. LINK: You should have presented that.
17 Second of all, I was impressed with the ability of the
18 bone marrow transplant community to do study with soft-19
tissue endpoints, a lot of patients, a “New England
20 Journal of Medicine” article, very prompt approval.
21 I’m just wondering why you’re so discouraged
22 about doing a trial like this? Admittedly, not
Page 148 Dr. Mcdonald from the Fred Hutchinson Center in Seattle again explains why it would be difficult to run the trials in acute GVHD, and explains that a prophylaxis trial would be the proper trial to run, but the FDA doesn't like mixing endpoints. Dr Pazdur chimes in, that he is open to negotiation
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1 everybody gets bowel GVH. But if you’re transplanting
2 60-year-olds, you probably will get a lot of it. I’m
3 just wondering why you’re so pessimistic about getting
4 it done? We’re going to do it in pediatrics, and we
5 don’t have that many patients.
6 DR. McDONALD: I’m pessimistic about doing a
7 placebo-controlled trial because I don’t think we can
8 get our IRB to approve one based on these data. I think
9 there are other options.
10 I mean, we have thought about a prophylaxis
11 trial, for example, but that’s a different indication,
12 though. This indication is for treatment of acute
13 graft-versus-host disease. A prophylaxis trial is for
14 prophylaxis of acute graft-versus-host disease.
15 From the FDA’s comments, you don’t like
16 merging of different kinds of trials to come to a
17 conclusion. That would take, what, two placebo-18
controlled prophylaxis trials for that --
19 DR. PAZDUR: We are always open for
20 negotiations.
21 (General laughter.)
22 DR. McDONALD: All right. That’s one thought,
Page 149 to 152 is basically the panel members all admitting that a prophlyaxis trial would be the way to go. Of course how does the drug get approved in acute GVHD if you run a prophylaxis trial.
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1 everybody gets bowel GVH. But if you’re transplanting
2 60-year-olds, you probably will get a lot of it. I’m
3 just wondering why you’re so pessimistic about getting
4 it done? We’re going to do it in pediatrics, and we
5 don’t have that many patients.
6 DR. McDONALD: I’m pessimistic about doing a
7 placebo-controlled trial because I don’t think we can
8 get our IRB to approve one based on these data. I think
9 there are other options.
10 I mean, we have thought about a prophylaxis
11 trial, for example, but that’s a different indication,
12 though. This indication is for treatment of acute
13 graft-versus-host disease. A prophylaxis trial is for
14 prophylaxis of acute graft-versus-host disease.
15 From the FDA’s comments, you don’t like
16 merging of different kinds of trials to come to a
17 conclusion. That would take, what, two placebo-18
controlled prophylaxis trials for that --
19 DR. PAZDUR: We are always open for
20 negotiations.
21 (General laughter.)
22 DR. McDONALD: All right. That’s one thought,
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1 that is, if this drug is as highly effective as a
2 topical therapy for treatment, it should be equally
3 effective and relatively nontoxic as prophylaxis. I
4 think that is one potential option.
5 CHAIRPERSON HUSSAIN: Gee, prophylaxis sounds
6 like very attractive. Why wait until an event happens?
7 I mean, that would be a clinically meaningful endpoint.
8 DR. McDONALD: I agree. Plus, it’s easier to
9 enroll patients who aren’t sick.
10 CHAIRPERSON HUSSAIN: Correct, correct.
11 DR. McDONALD: You can get a larger accrual.
12 Seven thousand patients should provide enough to enroll.
13 The hope there is that one would with effective
14 prophylaxis take what would ultimately be Stage IV and
15 turn them into Stage III, take Stage III and turn them
16 into Stage II, take Stage II and make them end up being
17 Stage I. I think that is a feasible thing. I can’t
18 speak for the company.
19 I think there are some financial issues. This
20 is a relatively small company, and I think that is a
21 consideration. In addition to the ethical and practical
22 issues, I think there are financial issues.
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1 DR. SCHABER: Dr. McDonald -- Chris Schaber,
2 president of Dor Bio Pharma -- that is in fact the
3 issue. For a company our size, we’ve put a lot of time,
4 effort, money, and resource into this study to support
5 Dr. McDonald and the rest of the investigators to go
6 after an indication that, quite honestly, big pharma
7 didn’t want to touch because it is a very small patient
8 population.
9 Although, as was outlined here and the experts
10 have spoken, we did not achieve the primary endpoint
11 without maybe the right sensoring or guarantee period.
12 With regard to the direct correlation of 80-
13 day as well as survival, which as Dr. Sullivan has
14 clearly stated in all of the trials that have been done
15 has never been seen, this is really an important trial
16 for us. To move forward from here and start over is
17 really economically not feasible for us with this
18 product.
19 CHAIRPERSON HUSSAIN: Dr. Mortimer.
20 DR. MORTIMER: Yes. My suggestion was going
21 to be a prophylactic study, but also it seems to me that
22 the biggest selling point of this drug is that it
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1 minimizes toxicity of steroids.
2 However the study is designed, a comparison of
3 this agent against steroids, if you demonstrate an
4 improved toxicity profile, I can’t but imagine that it
5 would move farther up in line for the indication
6 indicated here today.
7 CHAIRPERSON HUSSAIN: Okay. If there are no
8 other questions, I think that the FDA -- I’m sorry, Ms.
9 Haylock.
10 MS. HAYLOCK: I just wanted to suggest that
11 since some of the side-effects that were of concern to
12 people, for example, fatigue and then also some of the
13 other psychosocial issues, that some of our public
14 presenters brought up, there are quite a few
15 psychosocial tools or instrumentation available that
16 could be pretty easily incorporated into any trial. I
17 would suggest doing that. I think that would help as
18 well.
19 MR. SCHABER: May I say one more thing,
20 please?
21 CHAIRPERSON HUSSAIN: (Chairperson moving head
22 up and down.)
When has anyone ever seen Pazdur make a positive comment like this about a drug when there is a negative vote.
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1 in survival, and we’ve seen some survival advantages but
2 nothing spectacular, barring something like that, what
3 would be the point in bringing these discussions
4 forward?
5 DR. PAZDUR: I think to get public input on
6 and for discussion of points that may be missed by the
7 FDA reviewers. I am very thankful for the discussion
8 that we had today.
9 Personally, this drug because of this
10 discussion, irrespective of the vote, has a much
11 different impact in my mind. We will have discussions
12 internally on this drug and discuss the points that were
13 presented here.
14 CHAIRPERSON HUSSAIN: Thank you.
Pazdur will have the largest input on whether the drug gets approved. I think from the comments he made he likes the drug.
Dorb excerpts of ODAC transcript
I just figured it was worth posting again
Dr. Pazdur asks the panel to discuss whether another trial is feasible to run
1 large treatment, single-arm trial.
2 Here again, one of the questions that I have,
3 if that would be ongoing, would people even consider
4 doing another trial? Would another trial be feasible to
5 do? That’s another issue.
6 CHAIRPERSON HUSSAIN: Is this an issue you
7 want us to discuss now, or this is an issue that we want
8 to discuss after the vote?
9 DR. PAZDUR: Probably after the vote or it can
10 be discussed during the vote.
11 (General laughter.)
12 DR. PAZDUR: It’s really going to be part and
13 parcel of a decision here.
14 CHAIRPERSON HUSSAIN: Yes. Just a point of
15 clarification. If someone gets an IND for a specific
16 treatment, who pays for the cost of the drug?
17 DR. PAZDUR: Usually, the Sponsor would assume
18 the cost of that. Under the treatment IND mechanism,
19 however, which is a special type of expanded access
20 program, there can be some cost recovery on the part of
21 the Sponsor. We would entertain in a situation such as
22 this that type of program.
Mcdonal explains why trials using the drug for acute gvhd would be hard to run, because the doctors are formulating a drug themselves that isn't as good as Orbec but is better than placebo
1 in this group of patients for ethical and practical
2 reasons.
3 CHAIRPERSON HUSSAIN: Could you not consider
4 doing a trial, not placebo-controlled but with
5 equivalent doses of steroids to make the point that your
6 agent has a superior profile with regard to infections,
7 complications of steroids, and things of that sort? It
8 doesn’t have to be necessarily a survival-driven trial
9 but an efficacy trial?
10 DR. McDONALD: I think that is a
11 consideration, but actually there are some data that
12 bears on the question. If you look at the placebo arm
13 of 875, you will discover that 41 percent of people
14 required only 10 days of prednisone. If you look at the
15 placebo arm of the pivotal trial, 55 percent required
16 only 10 days of prednisone.
17 I think it is very difficult to argue that a
18 high-dose prednisone regiment would benefit any of those
19 patients who required only 10 days of prednisone. I
20 think the same ethical issues exist in doing a very
21 high-dose prednisone versus this approach.
22 We have already proved, I think, that the
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1 minimum prednisone approach protected by BDP has far
2 superior results to our 25-year standard of care. Again,
3 it is not the GVH that is killing people; it is the
4 treatment for GVH that’s doing the job.
5 I think we have adequately proved that BDP has
6 a steroid-sparing effect. I’m not sure I can go back 25
7 years in time and grab our old regimens. I am quite
8 convinced. I think it might well be unethical to do
9 that kind of a comparison.
10 DR. RODELL: Excuse me. Dr. Sullivan from
11 Duke was actually not involved in the trial.
12 CHAIRPERSON HUSSAIN: I just have another
13 question, though, please. If you say you don’t want to
14 go back to the past and grab old regimens, and if your
15 drug is currently not available on the market, and we
16 have heard that people use the oil-mixed product with
17 something, is that what people are currently using? Is
18 that what the alternative out there is?
19 DR. McDONALD: The alternative is what I call
20 the ad-hoc way of formulating something that is similar
21 to what we are using in these trials, that is, to use
22 the corn oil combined with budesonide.
the panel votes no
1 overwhelmingly we were against something and the FDA
2 approved it anyway.
3 (General laughter.)
4 CHAIRPERSON HUSSAIN: They don’t necessarily
5 always listen to us. Thank you.
6 If there are no other burning questions or
7 comments, I’m going to try to ask that we go ahead to
8 the vote.
9 Put the question up again, please.
10 (Staff complies.)
11 CHAIRPERSON HUSSAIN: We will begin around the
12 table. No description of why one is voting yes or no,
13 just the vote yes or no. Identify please yourself and
14 speak clearly into the microphone.
15 Dr. Link, can we begin with you, please?
16 DR. LINK: Michael Link. I vote no that it
17 has not shown substantial evidence.
18 MS. HAYLOCK: Haylock, no.
19 DR. HARRINGTON: No.
20 DR. MORTIMER: Mortimer, no.
21 CHAIRPERSON HUSSAIN: Hussain, no.
22 DR. RICHARDSON: Richardson, no.
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1 DR. PERRY: Perry, no.
2 DR. SPORTES: Sportes, yes.
3 DR. FLATAU: Flatau, yes.
4 CHAIRPERSON HUSSAIN: Two yes, seven no.
5 Dr. Pazdur, do you want us to go into the
6 second issue of design, of study design?
7 DR. PAZDUR: We’ve already started the
8 discussion.
9 CHAIRPERSON HUSSAIN: Yes, but I thought it
10 was for discussion, not for a vote.
11 DR. PAZDUR: We’ve already started the
12 discussion.
13 CHAIRPERSON HUSSAIN: In terms of what ideal
14 study design is?
15 DR. PAZDUR: Yes.
16 CHAIRPERSON HUSSAIN: Maybe I can begin and
17 ask the sponsor first, when you look at your data and
18 you look at what you started with and then what you got,
19 what do you think, like in your gut with yourself
20 looking at this, where do you think your strongest point
21 was? Because that seems to me where you should then go
22 back to look at that area because that may be where
Hussein explains that you couldn't run a trial in this population that could be stratified equally.
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1 between treatment arms, it would require, roughly, 160
2 deaths and a true hazard ratio of 0.55 would require,
3 roughly, 120 deaths. The accrual would be quite
4 substantial.
5 CHAIRPERSON HUSSAIN: Any words of wisdom from
6 committee members as far as study designs or suggestions
7 to the Sponsor or to the FDA with regard to what they
8 should advise them to do?
9 Sir?
10 DR. FLATAU: Yes. I would like to think at
11 least a secondary endpoint of overall survival at least
12 at one year, if not longer, would be interesting.
13 CHAIRPERSON HUSSAIN: I guess the only concern
14 I have about survival is unless you make the population
15 entering very uniform with the same diseases, the same
16 regimen, the same everything, you are never going to be
17 able to interpret the results, it would seem to me,
18 unless you stratify very clear where you include several
19 groups of people clearly stratified equal in each arm.
20 I can’t see how you would do it if you argue that we
21 don’t have a huge population.
Dr. Sportes the only transplant doctor on the panel and one of the positive votes explained that the 80 day endpoint which was met clinically means more than the 50 day endpoint
22 DR. SPORTES: Actually, I was wondering and I
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1 should have asked earlier why the secondary endpoint was
2 not the primary endpoint.
3 It seems to me from a transplant perspective
4 that a followup at 80 days is probably the strongest
5 endpoint, which is why I voted yes is because I think to
6 me conceptually this is much more a reflection of the
7 entire intervention. Why was that not chosen? I just
8 seek some explanation.
9 DR. RODELL: May I respond to that?
10 CHAIRPERSON HUSSAIN: Yes.
11 DR. RODELL: I think it’s important to
12 recognize the history of how this drug was developed.
13 The initial study, the initial efficacy study was Study
14 875 that was done essentially on a completely open
15 field, that is, this type of study had never been done
16 before and so the 30-day endpoint was selected in that
17 study, essentially, arbitrarily.
18 Once the results of that study were know, Dr.
19 McDonald spoke with and talked to the FDA, shared with
20 them the results of that study and began to design the
21 02 Study.
22 The two components with respect to efficacy
Dr. Link explains that the first 10 days on Orbec should be a guarantee period and is surprised that they didn't show this slide before the vote.
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1 The practicality, even without getting into
2 the economics of doing another study, is going to be a
3 significant issue in terms of the future development of
4 the drug.
5 CHAIRPERSON HUSSAIN: Thank you.
6 Any other comments?
7 (No verbal response.)
8 CHAIRPERSON HUSSAIN: Well, we will begin with
9 Dr. Link, then, and we will go around the table.
10 DR. LINK: I have two. The first is a
11 question of what if you actually -- the mistake maybe
12 was that you started the clock too soon in terms of you
13 started on the day of randomization. Either if you if
14 you had randomized after the 10 days and only randomized
15 responders -- Dave, you’re not going to shoot me here,
16 are you?
17 The second things is to actually do an
18 analysis, start the clock when they achieve remission
19 and throw out people who didn’t achieve remission, which
20 is often done in transplant studies. That would be one
21 suggestion.
22 What does it look like? Does it look better?
1 Does it look like you had achieved your goal, just out
2 of curiosity?
3 DR. RODELL: Yes, let me ask Mr. Cruickshank
4 to address that.
5 (PowerPoint presentation is in progress.)
6 MR. CRUICKSHANK: Going back to that question
7 about, what is the effect of those early failures, we
8 did do an analysis to look at the effect whereby
9 patients who failed during the 10-day high-dose
10 induction period of prednisone.
11 If you sensor the patients at the time of
12 treatment failure, you can see here that we lose the
13 effect of the crossing Kaplan-Meier curves. We have a
14 fairly clear, sustained difference between the arms at
15 day 50 as well as day 80.
16 DR. LINK: You should have presented that.
17 Second of all, I was impressed with the ability of the
18 bone marrow transplant community to do study with soft-19
tissue endpoints, a lot of patients, a “New England
20 Journal of Medicine” article, very prompt approval.
21 I’m just wondering why you’re so discouraged
22 about doing a trial like this? Admittedly, not
Page 148 Dr. Mcdonald from the Fred Hutchinson Center in Seattle again explains why it would be difficult to run the trials in acute GVHD, and explains that a prophylaxis trial would be the proper trial to run, but the FDA doesn't like mixing endpoints. Dr Pazdur chimes in, that he is open to negotiation
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1 everybody gets bowel GVH. But if you’re transplanting
2 60-year-olds, you probably will get a lot of it. I’m
3 just wondering why you’re so pessimistic about getting
4 it done? We’re going to do it in pediatrics, and we
5 don’t have that many patients.
6 DR. McDONALD: I’m pessimistic about doing a
7 placebo-controlled trial because I don’t think we can
8 get our IRB to approve one based on these data. I think
9 there are other options.
10 I mean, we have thought about a prophylaxis
11 trial, for example, but that’s a different indication,
12 though. This indication is for treatment of acute
13 graft-versus-host disease. A prophylaxis trial is for
14 prophylaxis of acute graft-versus-host disease.
15 From the FDA’s comments, you don’t like
16 merging of different kinds of trials to come to a
17 conclusion. That would take, what, two placebo-18
controlled prophylaxis trials for that --
19 DR. PAZDUR: We are always open for
20 negotiations.
21 (General laughter.)
22 DR. McDONALD: All right. That’s one thought,
Page 149 to 152 is basically the panel members all admitting that a prophlyaxis trial would be the way to go. Of course how does the drug get approved in acute GVHD if you run a prophylaxis trial.
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1 everybody gets bowel GVH. But if you’re transplanting
2 60-year-olds, you probably will get a lot of it. I’m
3 just wondering why you’re so pessimistic about getting
4 it done? We’re going to do it in pediatrics, and we
5 don’t have that many patients.
6 DR. McDONALD: I’m pessimistic about doing a
7 placebo-controlled trial because I don’t think we can
8 get our IRB to approve one based on these data. I think
9 there are other options.
10 I mean, we have thought about a prophylaxis
11 trial, for example, but that’s a different indication,
12 though. This indication is for treatment of acute
13 graft-versus-host disease. A prophylaxis trial is for
14 prophylaxis of acute graft-versus-host disease.
15 From the FDA’s comments, you don’t like
16 merging of different kinds of trials to come to a
17 conclusion. That would take, what, two placebo-18
controlled prophylaxis trials for that --
19 DR. PAZDUR: We are always open for
20 negotiations.
21 (General laughter.)
22 DR. McDONALD: All right. That’s one thought,
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1 that is, if this drug is as highly effective as a
2 topical therapy for treatment, it should be equally
3 effective and relatively nontoxic as prophylaxis. I
4 think that is one potential option.
5 CHAIRPERSON HUSSAIN: Gee, prophylaxis sounds
6 like very attractive. Why wait until an event happens?
7 I mean, that would be a clinically meaningful endpoint.
8 DR. McDONALD: I agree. Plus, it’s easier to
9 enroll patients who aren’t sick.
10 CHAIRPERSON HUSSAIN: Correct, correct.
11 DR. McDONALD: You can get a larger accrual.
12 Seven thousand patients should provide enough to enroll.
13 The hope there is that one would with effective
14 prophylaxis take what would ultimately be Stage IV and
15 turn them into Stage III, take Stage III and turn them
16 into Stage II, take Stage II and make them end up being
17 Stage I. I think that is a feasible thing. I can’t
18 speak for the company.
19 I think there are some financial issues. This
20 is a relatively small company, and I think that is a
21 consideration. In addition to the ethical and practical
22 issues, I think there are financial issues.
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1 DR. SCHABER: Dr. McDonald -- Chris Schaber,
2 president of Dor Bio Pharma -- that is in fact the
3 issue. For a company our size, we’ve put a lot of time,
4 effort, money, and resource into this study to support
5 Dr. McDonald and the rest of the investigators to go
6 after an indication that, quite honestly, big pharma
7 didn’t want to touch because it is a very small patient
8 population.
9 Although, as was outlined here and the experts
10 have spoken, we did not achieve the primary endpoint
11 without maybe the right sensoring or guarantee period.
12 With regard to the direct correlation of 80-
13 day as well as survival, which as Dr. Sullivan has
14 clearly stated in all of the trials that have been done
15 has never been seen, this is really an important trial
16 for us. To move forward from here and start over is
17 really economically not feasible for us with this
18 product.
19 CHAIRPERSON HUSSAIN: Dr. Mortimer.
20 DR. MORTIMER: Yes. My suggestion was going
21 to be a prophylactic study, but also it seems to me that
22 the biggest selling point of this drug is that it
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1 minimizes toxicity of steroids.
2 However the study is designed, a comparison of
3 this agent against steroids, if you demonstrate an
4 improved toxicity profile, I can’t but imagine that it
5 would move farther up in line for the indication
6 indicated here today.
7 CHAIRPERSON HUSSAIN: Okay. If there are no
8 other questions, I think that the FDA -- I’m sorry, Ms.
9 Haylock.
10 MS. HAYLOCK: I just wanted to suggest that
11 since some of the side-effects that were of concern to
12 people, for example, fatigue and then also some of the
13 other psychosocial issues, that some of our public
14 presenters brought up, there are quite a few
15 psychosocial tools or instrumentation available that
16 could be pretty easily incorporated into any trial. I
17 would suggest doing that. I think that would help as
18 well.
19 MR. SCHABER: May I say one more thing,
20 please?
21 CHAIRPERSON HUSSAIN: (Chairperson moving head
22 up and down.)
When has anyone ever seen Pazdur make a positive comment like this about a drug when there is a negative vote.
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1 in survival, and we’ve seen some survival advantages but
2 nothing spectacular, barring something like that, what
3 would be the point in bringing these discussions
4 forward?
5 DR. PAZDUR: I think to get public input on
6 and for discussion of points that may be missed by the
7 FDA reviewers. I am very thankful for the discussion
8 that we had today.
9 Personally, this drug because of this
10 discussion, irrespective of the vote, has a much
11 different impact in my mind. We will have discussions
12 internally on this drug and discuss the points that were
13 presented here.
14 CHAIRPERSON HUSSAIN: Thank you.
Pazdur will have the largest input on whether the drug gets approved. I think from the comments he made he likes the drug.
In the area that I live in Nassau County the teachers make nearly a 100,000 a year with pensions of at least 80m
they get great medical benefits.
It doesn't mean the kids are getting a better education, it just makes the teachers in the city jealous that they aren't working in the suburbs
Eating Made Simple
http://www.sciam.com/print_version.cfm?articleID=3CDDB14C-E7F2-99DF-39AC2C4049B2F6C0
How do you cope with a mountain of conflicting diet advice?
By Marion Nestle
As a nutrition professor, I am constantly asked why nutrition advice seems to change so much and why experts so often disagree. Whose information, people ask, can we trust? I’m tempted to say, “Mine, of course,” but I understand the problem. Yes, nutrition advice seems endlessly mired in scientific argument, the self-interest of food companies and compromises by government regulators. Nevertheless, basic dietary principles are not in dispute: eat less; move more; eat fruits, vegetables and whole grains; and avoid too much junk food.
“Eat less” means consume fewer calories, which translates into eating smaller portions and steering clear of frequent between-meal snacks. “Move more” refers to the need to balance calorie intake with physical activity. Eating fruits, vegetables and whole grains provides nutrients unavailable from other foods. Avoiding junk food means to shun “foods of minimal nutritional value”—highly processed sweets and snacks laden with salt, sugars and artificial additives. Soft drinks are the prototypical junk food; they contain sweeteners but few or no nutrients.
If you follow these precepts, other aspects of the diet matter much less. Ironically, this advice has not changed in years. The noted cardiologist Ancel Keys (who died in 2004 at the age of 100) and his wife, Margaret, suggested similar principles for preventing coronary heart disease nearly 50 years ago.
But I can see why dietary advice seems like a moving target. Nutrition research is so difficult to conduct that it seldom produces unambiguous results. Ambiguity requires interpretation. And interpretation is influenced by the individual’s point of view, which can become thoroughly entangled with the science.
Nutrition Science Challenges
This scientific uncertainty is not overly surprising given that humans eat so many different foods. For any individual, the health effects of diets are modulated by genetics but also by education and income levels, job satisfaction, physical fitness, and the use of cigarettes or alcohol. To simplify this situation, researchers typically examine the effects of single dietary components one by one.
Studies focusing on one nutrient in isolation have worked splendidly to explain symptoms caused by deficiencies of vitamins or minerals. But this approach is less useful for chronic conditions such as coronary heart disease and diabetes that are caused by the interaction of dietary, genetic, behavioral and social factors. If nutrition science seems puzzling, it is because researchers typically examine single nutrients detached from food itself, foods separate from diets, and risk factors apart from other behaviors. This kind of research is “reductive” in that it attributes health effects to the consumption of one nutrient or food when it is the overall dietary pattern that really counts most.
For chronic diseases, single nutrients usually alter risk by amounts too small to measure except through large, costly population studies. As seen recently in the Women’s Health Initiative, a clinical trial that examined the effects of low-fat diets on heart disease and cancer, participants were unable to stick with the restrictive dietary protocols. Because humans cannot be caged and fed measured formulas, the diets of experimental and control study groups tend to converge, making differences indistinguishable over the long run—even with fancy statistics.
It’s the Calories
Food companies prefer studies of single nutrients because they can use the results to sell products. Add vitamins to candies, and you can market them as health foods. Health claims on the labels of junk foods distract consumers from their caloric content. This practice matters because when it comes to obesity—which dominates nutrition problems even in some of the poorest countries of the world—it is the calories that count. Obesity arises when people consume significantly more calories than they expend in physical activity.
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America’s obesity rates began to rise sharply in the early 1980s. Sociologists often attribute the “calories in” side of this trend to the demands of an overworked population for convenience foods—prepared, packaged products and restaurant meals that usually contain more calories than home-cooked meals.
But other social forces also promoted the calorie imbalance. The arrival of the Reagan administration in 1980 increased the pace of industry deregulation, removing controls on agricultural production and encouraging farmers to grow more food. Calories available per capita in the national food supply (that produced by American farmers, plus imports, less exports) rose from 3,200 a day in 1980 to 3,900 a day two decades later.
The early 1980s also marked the advent of the “shareholder value movement” on Wall Street. Stockholder demands for higher short-term returns on investments forced food companies to expand sales in a marketplace that already contained excessive calories. Food companies responded by seeking new sales and marketing opportunities. They encouraged formerly shunned practices that eventually changed social norms, such as frequent between-meal snacking, eating in book and clothing stores, and serving larger portions. The industry continued to sponsor organizations and journals that focus on nutrition-related subjects and intensified its efforts to lobby government for favorable dietary advice. Then and now food lobbies have promoted positive interpretations of scientific studies, sponsored research that can be used as a basis for health claims, and attacked critics, myself among them, as proponents of “junk science.” If anything, such activities only add to public confusion.
Supermarkets as “Ground Zero”
No matter whom I speak to, I hear pleas for help in dealing with supermarkets, considered by shoppers as “ground zero” for distinguishing health claims from scientific advice. So I spent a year visiting supermarkets to help people think more clearly about food choices. The result was my book What to Eat.
Supermarkets provide a vital public service but are not social services agencies. Their job is to sell as much food as possible. Every aspect of store design—from shelf position to background music—is based on marketing research. Because this research shows that the more products customers see, the more they buy, a store’s objective is to expose shoppers to the maximum number of products they will tolerate viewing.
If consumers are confused about which foods to buy, it is surely because the choices require knowledge of issues that are not easily resolved by science and are strongly swayed by social and economic considerations. Such decisions play out every day in every store aisle.
Are Organics Healthier?
Organic foods are the fastest-growing segment of the industry, in part because people are willing to pay more for foods that they believe are healthier and more nutritious. The U.S. Department of Agriculture forbids producers of “Certified Organic” fruits and vegetables from using synthetic pesticides, herbicides, fertilizers, genetically modified seeds, irradiation or fertilizer derived from sewage sludge. It licenses inspectors to ensure that producers follow those rules. Although the USDA is responsible for organics, its principal mandate is to promote conventional agriculture, which explains why the department asserts that it “makes no claims that organically produced food is safer or more nutritious than conventionally produced food. Organic food differs from conventionally grown food in the way it is grown, handled and processed.”
This statement implies that such differences are unimportant. Critics of organic foods would agree; they question the reliability of organic certification and the productivity, safety and health benefits of organic production methods. Meanwhile the organic food industry longs for research to address such criticisms, but studies are expensive and difficult to conduct. Nevertheless, existing research in this area has established that organic farms are nearly as productive as conventional farms, use less energy and leave soils in better condition. People who eat foods grown without synthetic pesticides ought to have fewer such chemicals in their bodies, and they do. Because the organic rules require pretreatment of manure and other steps to reduce the amount of pathogens in soil treatments, organic foods should be just as safe—or safer—than conventional foods.
Similarly, organic foods ought to be at least as nutritious as conventional foods. And proving organics to be more nutritious could help justify their higher prices. For minerals, this task is not difficult. The mineral content of plants depends on the amounts present in the soil in which they are grown. Organic foods are cultivated in richer soils, so their mineral content is higher.
But differences are harder to demonstrate for vitamins or antioxidants (plant substances that reduce tissue damage induced by free radicals); higher levels of these nutrients relate more to a food plant’s genetic strain or protection from unfavorable conditions after harvesting than to production methods. Still, preliminary studies show benefits: organic peaches and pears contain greater quantities of vitamins C and E, and organic berries and corn contain more antioxidants.
Further research will likely confirm that organic foods contain higher nutrient levels, but it is unclear whether these nutrients would make a measurable improvement in health. All fruits and vegetables contain useful nutrients, albeit in different combinations and concentrations. Eating a variety of food plants is surely more important to health than small differences in the nutrient content of any one food. Organics may be somewhat healthier to eat, but they are far less likely to damage the environment, and that is reason enough to choose them at the supermarket.
Dairy and Calcium
Scientists cannot easily resolve questions about the health effects of dairy foods. Milk has many components, and the health of people who consume milk or dairy foods is influenced by everything else they eat and do. But this area of research is especially controversial because it affects an industry that vigorously promotes dairy products as beneficial and opposes suggestions to the contrary.
Dairy foods contribute about 70 percent of the calcium in American diets. This necessary mineral is a principal constituent of bones, which constantly lose and regain calcium during normal metabolism. Diets must contain enough calcium to replace losses, or else bones become prone to fracture. Experts advise consumption of at least one gram of calcium a day to replace everyday losses. Only dairy foods provide this much calcium without supplementation.
But bones are not just made of calcium; they require the full complement of essential nutrients to maintain strength. Bones are stronger in people who are physically active and who do not smoke cigarettes or drink much alcohol. Studies examining the effects of single nutrients in dairy foods show that some nutritional factors—magnesium, potassium, vitamin D and lactose, for example—promote calcium retention in bones. Others, such as protein, phosphorus and sodium, foster calcium excretion. So bone strength depends more on overall patterns of diet and behavior than simply on calcium intake.
Populations that do not typically consume dairy products appear to exhibit lower rates of bone fracture despite consuming far less calcium than recommended. Why this is so is unclear. Perhaps their diets contain less protein from meat and dairy foods, less sodium from processed foods and less phosphorus from soft drinks, so they retain calcium more effectively. The fact that calcium balance depends on multiple factors could explain why rates of osteoporosis (bone density loss) are highest in countries where people eat the most dairy foods. Further research may clarify such counterintuitive observations.
In the meantime, dairy foods are fine to eat if you like them, but they are not a nutritional requirement. Think of cows: they do not drink milk after weaning, but their bones support bodies weighing 800 pounds or more. Cows feed on grass, and grass contains calcium in small amounts—but those amounts add up. If you eat plenty of fruits, vegetables and whole grains, you can have healthy bones without having to consume dairy foods.
A Meaty Debate
Critics point to meat as the culprit responsible for elevating blood cholesterol, along with raising risks for heart disease, cancer and other conditions. Supporters cite the lack of compelling science to justify such allegations; they emphasize the nutritional benefits of meat protein, vitamins and minerals. Indeed, studies in developing countries demonstrate health improvements when growing children are fed even small amounts of meat.
But because bacteria in a cow’s rumen attach hydrogen atoms to unsaturated fatty acids, beef fat is highly saturated—the kind of fat that increases the risk of coronary heart disease. All fats and oils contain some saturated fatty acids, but animal fats, especially those from beef, have more saturated fatty acids than vegetable fats. Nutritionists recommend eating no more than a heaping tablespoon (20 grams) of saturated fatty acids a day. Beef eaters easily meet or exceed this limit. The smallest McDonald’s cheeseburger contains 6 grams of saturated fatty acids, but a Hardee’s Monster Thickburger has 45 grams.
Why meat might boost cancer risks, however, is a matter of speculation. Scientists began to link meat to cancer in the 1970s, but even after decades of subsequent research they remain unsure if the relevant factor might be fat, saturated fat, protein, carcinogens or something else related to meat. By the late 1990s experts could conclude only that eating beef probably increases the risk of colon and rectal cancers and possibly enhances the odds of acquiring breast, prostate and perhaps other cancers. Faced with this uncertainty, the American Cancer Society suggests selecting leaner cuts, smaller portions and alternatives such as chicken, fish or beans—steps consistent with today’s basic advice about what to eat.
Fish and Heart Disease
Fatty fish are the most important sources of long-chain omega-3 fatty acids. In the early 1970s Danish investigators observed surprisingly low frequencies of heart disease among indigenous populations in Greenland that typically ate fatty fish, seals and whales. The researchers attributed the protective effect to the foods’ content of omega-3 fatty acids. Some subsequent studies—but by no means all—confirm this idea.
Because large, fatty fish are likely to have accumulated methylmercury and other toxins through predation, however, eating them raises questions about the balance between benefits and risks. Understandably, the fish industry is eager to prove that the health benefits of omega-3s outweigh any risks from eating fish.
Even independent studies on omega-3 fats can be interpreted differently. In 2004 the National Oceanic and Atmospheric Administration—for fish, the agency equivalent to the USDA—asked the Institute of Medicine (IOM) to review studies of the benefits and risks of consuming seafood. The ensuing review of the research on heart disease risk illustrates the challenge such work poses for interpretation.
The IOM’s October 2006 report concluded that eating seafood reduces the risk of heart disease but judged the studies too inconsistent to decide if omega-3 fats were responsible. In contrast, investigators from the Harvard School of Public Health published a much more positive report in the Journal of the American Medical Association that same month. Even modest consumption of fish omega-3s, they stated, would cut coronary deaths by 36 percent and total mortality by 17 percent, meaning that not eating fish would constitute a health risk.
Differences in interpretation explain how distinguished scientists could arrive at such different conclusions after considering the same studies. The two groups, for example, had conflicting views of earlier work published in March 2006 in the British Medical Journal. That study found no overall effect of omega-3s on heart disease risk or mortality, although a subset of the original studies displayed a 14 percent reduction in total mortality that did not reach statistical significance. The IOM team interpreted the “nonsignificant” result as evidence for the need for caution, whereas the Harvard group saw the data as consistent with studies reporting the benefits of omega-3s. When studies present inconsistent results, both interpretations are plausible. I favor caution in such situations, but not everyone agrees.
Because findings are inconsistent, so is dietary advice about eating fish. The American Heart Association recommends that adults eat fatty fish at least twice a week, but U.S. dietary guidelines say: “Limited evidence suggests an association between consumption of fatty acids in fish and reduced risks of mortality from cardiovascular disease for the general population ... however, more research is needed.” Whether or not fish uniquely protects against heart disease, seafood is a delicious source of many nutrients, and two small servings per week of the less predatory classes of fish are unlikely to cause harm.
Sodas and Obesity
Sugars and corn sweeteners account for a large fraction of the calories in many supermarket foods, and virtually all the calories in drinks—soft, sports and juice—come from added sugars.
In a trend that correlates closely with rising rates of obesity, daily per capita consumption of sweetened beverages has grown by about 200 calories since the early 1980s. Although common sense suggests that this increase might have something to do with weight gain, beverage makers argue that studies cannot prove that sugary drinks alone—independent of calories or other foods in the diet—boost the risk of obesity. The evidence, they say correctly, is circumstantial. But pediatricians often see obese children in their practices who consume more than 1,000 calories a day from sweetened drinks alone, and several studies indicate that children who habitually consume sugary beverages take in more calories and weigh more than those who do not.
Nevertheless, the effects of sweetened drinks on obesity continue to be subject to interpretation. In 2006, for example, a systematic review funded by independent sources found sweetened drinks to promote obesity in both children and adults. But a review that same year sponsored in part by a beverage trade association concluded that soft drinks have no special role in obesity. The industry-funded researchers criticized existing studies as being short-term and inconclusive, and pointed to studies finding that people lose weight when they substitute sweetened drinks for their usual meals.
These differences imply the need to scrutinize food industry sponsorship of research itself. Although many researchers are offended by suggestions that funding support might affect the way they design or interpret studies, systematic analyses say otherwise. In 2007 investigators classified studies of the effects of sweetened and other beverages on health according to who had sponsored them. Industry-supported studies were more likely to yield results favorable to the sponsor than those funded by independent sources. Even though scientists may not be able to prove that sweetened drinks cause obesity, it makes sense for anyone interested in losing weight to consume less of them.
The examples I have discussed illustrate why nutrition science seems so controversial. Without improved methods to ensure compliance with dietary regimens, research debates are likely to rage unabated. Opposing points of view and the focus of studies and food advertising on single nutrients rather than on dietary patterns continue to fuel these disputes. While we wait for investigators to find better ways to study nutrition and health, my approach—eat less, move more, eat a largely plant-based diet, and avoid eating too much junk food—makes sense and leaves you plenty of opportunity to enjoy your dinner.
© 1996-2007 Scientific American, Inc. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Can Fat Be Fit?
http://www.sciam.com/print_version.cfm?articleID=3CCA0E80-E7F2-99DF-3ABA97D5027BF4EE
A well-publicized study and a spate of popular books raise questions about the ill effects of being overweight. Their conclusions are probably wrong
By Paul Raeburn
Two years ago Katherine M. Flegal, a researcher at the Centers for Disease Control and Prevention, did a new statistical analysis of national survey data on obesity and came to a startling conclusion: mildly overweight adults had a lower risk of dying than those at so-called healthy weights.
Decades of research and thousands of studies have suggested precisely the opposite: that being even a little overweight is bad and that being obese is worse. The distinction between overweight and obese—which are sometimes both classified under the rubric of obesity—can be confusing. It relates to the measure called body mass index (BMI), derived by dividing one’s weight in kilograms by the square of one’s height in meters. A myriad of Internet-based calculators will handle the math for you. The only thing to remember is that a BMI of at least 25 but less than 30 is considered overweight, and one of 30 or more is characterized as obese.
The long-established conventional wisdom holds that Americans carrying excess fat are at increased risk of death from heart disease, diabetes and various kinds of cancer. And those who do not die of obesity-related ailments can possibly look forward to a variety of other unpleasant consequences of their weight, including diabetes and its complications, such as the loss of an arm or leg, blindness and kidney failure. That has been the consensus view of most experts for decades, and it has not changed.
Just as Flegal’s study appeared, a series of books—by lawyers, journalists, political scientists and other academics outside the medical profession—was published, all challenging conventional wisdom on obesity. Fat, the critics said, was not as bad as we had been led to believe. Furthermore, they said, the research community that condemned obesity had a financial stake in that point of view because of the scientists’ complex ties to drugmakers and weight-loss clinics.
The flow of critical books has continued. Earlier this year Barry Glassner, author of the best-selling book The Culture of Fear (Basic Books, 2000), published The Gospel of Food: Everything You Think You Know About Food Is Wrong (Ecco, 2007). He argues that if we paid more attention to enjoying our food, rather than dieting and counting calories, we would be happier and healthier. It is an appealing argument, but Glassner, a sociologist at the University of Southern California, has not done any research studies to show whether it is true.
The stakes in this debate are high. A major thrust of the nation’s disease prevention efforts are aimed at ending what orthodox researchers say is an epidemic of obesity. If being overweight or obese is as harmful as these investigators say, the associated health care costs constitute a substantial drag on the American economy. The CDC estimated in 2004 that obesity’s costs in health care and lost productivity amount to $75 billion annually. Put an end to the fattening of America, these researchers say, and Americans will be healthier, live longer and pay less for their medical care. We might even see gains in American competitiveness, with growth in jobs and wages.
If too much fat is not an important cause of heart disease and other serious illnesses—the possibility raised by Flegal and other critics—then efforts to trim American waistlines are entirely misplaced. Many of the leaders in the obesity research community dismiss the criticism. “It’s complete nonsense, and it’s obviously complete nonsense, and it’s very easy to explain why some people have gone astray,” says Meir Stampfer, a professor of nutrition and epidemiology at the Harvard School of Public Health. Stampfer and his Harvard colleague Walter Willett have done a series of decades-long studies involving hundreds of thousands of people that have laid the foundation for much of what is known about the dangers of being overweight or obese.
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Stampfer cites the Flegal study as a prime example of the errors the critics make. The reason being overweight seemed to reduce mortality is because Flegal used the wrong comparison group, he says. The lean group in her study included smokers and people with chronic illnesses—both of whom have increased mortality risks, but not because they are slim. “When you get sick, you lose weight, and you die,” Stampfer says. Compared with those who are smokers or chronically ill, people who are overweight come out looking better than they should.
Willett points to a November 2006 study by James A. Greenberg, a researcher at Brooklyn College, to prove his point. Greenberg performed a similar statistical analysis to Flegal’s, this time adjusting for factors such as a history of serious illness. When he did, the number of extra deaths for the obese—compared to those with a “healthy” weight—tripled. And he found a significant increased mortality risk in those who were merely overweight, contrary to Flegal’s finding that being overweight lowered the risk of death.
Flegal has acknowledged that she did not exclude the chronically ill from her study but argued in a follow-up report that she had done further analyses that showed it would not have made a difference. The disagreement turns on subtle statistical arguments. What is clear, however, is that Flegal’s paper is one of a handful that contradict many studies that support the conclusion that being overweight is harmful. Flegal is not necessarily wrong, but the preponderance of evidence clearly points in the other direction.
Willett thinks this assertion is simply the latest recycling of the notion that Americans have been somehow duped about the risks of obesity. “About every 10 years this idea comes along that says it’s better to be overweight. And we have to stomp it out,” he says. Willett’s research has identified profound advantages to keeping weight down—even below the so-called healthy levels.
Many Americans find it difficult to get under a BMI of 25, the border between the overweight and healthy groups. But Willett’s work suggests that losing more weight is even better. To take one example, people with a BMI of 20 who gain enough to reach a BMI of 25 have quadrupled their risk of diabetes, Willett says. “If they go up over a BMI of 30, they’ve increased their risk of diabetes 30- to 60-fold,” he says. “And diabetes is not a good thing to have.”
So, in light of conflicting evidence, what is the state-of-the-art summary of the conventional wisdom? Willett puts it this way: keep an eye on three numbers. One is your BMI—keep it within the normal range (20 to 24.9), and preferably near the low end of that range. The second is your weight change after age 20. Although obesity has become increasingly common in children, most people who are now adults were probably close to their proper weight when they were 20, he says. Try to get back to that. The third number is waist circumference—if your belt size has increased since you were 20, that is something to reverse, too.
The consequences of working on these three numbers, he says, will be “huge benefits in health.” But even small reductions in weight are beneficial. “If people can lose 5 to 10 percent of their weight, they will have done themselves a huge favor. If they can take another step, another 5 to 10 percent, they will have done themselves another favor.” Some of the details have changed—but that is the same advice obesity experts have been dispensing for years.
More to Explore
Guidelines for Healthy Weight. Walter C. Willett et al. in New England Journal of Medicine, Vol. 341, No. 6, pages 427–434; August 5, 1999.
Excess Deaths Associated with Underweight, Overweight, and Obesity. Katherine M. Flegal et al. in Journal of the American Medical Association, Vol. 293, No. 15, pages 1861–1867; April 20, 2005.
Obesity: An Overblown Epidemic? W. Wayt Gibbs in Scientific American, Vol. 292, No. 6; pages 70–77; June 2005.
Correcting Biases in Estimates of Mortality Attributable to Obesity. James A. Greenberg in Obesity, Vol. 14, No. 11, pages 2071–2079; November 2006.
© 1996-2007 Scientific American, Inc. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
This is Your Brain on Food (extended version)
http://www.sciam.com/print_version.cfm?articleID=4B70503C-E7F2-99DF-3495C8EC41668EC8
Neuroimaging reveals a shared basis for chocoholia and drug addiction
By Kristin Leutwyler Ozelli
Mounting evidence shows that compulsive eating and drug abuse engage some of the same brain circuits in similar ways, offering a new angle for understanding and treating obesity. In an interview with Scientific American, Nora D. Volkow, director of the National Institute on Drug Abuse and a pioneer in the study of addiction, explains.
How do foods and drugs affect the brain in the same way?
The system in the brain that both drugs and food activate is basically the circuitry that evolved to reward behaviors that are essential for our survival. One of the reasons why humans are attracted to food is because of its rewarding, pleasurable properties. When we experience pleasure, our brains learn to associate the pleasurable experience with the cues and conditions that predict it. In other words, the brain remembers not just what the food tasted like but also the sensation of pleasure itself, and the cues or behaviors that preceded it. That memory becomes stronger and stronger as the cycle of predicting, seeking and obtaining pleasure becomes more reliable. When you remember that food, you also automatically expect the pleasure that comes from it. So when you like something very much, the mere fact of being re-exposed to it, even if it is out of reach, will trigger the desire to get it. In scientific terms, we call this process conditioning.
Conditioned cues or memories are very powerful and can profoundly affect our behavior. And when conditioning occurs to a positive stimulus, such as food, you are much more likely to repeat a particular action to obtain it. Drugs are particularly effective as conditioning stimuli, primarily by virtue of their chemical properties. They can directly stimulate areas of the brain involved with pleasure in a way that is more efficient than natural reinforcers, such as food or sex. You get an exaggerated response (supraphysiological) partly because the drug can get to the brain very fast, in a matter of seconds. With natural reinforcers the process of activating the reward pathway is more prolonged. Importantly, the conditioning that takes place links the behavior not just to the stimulus itself but to the environment and other cues that might have been only peripherally associated with it.
That’s exactly what nature intended: if the behavior necessary to seek a pleasurable experience was triggered exclusively by the object, the conditioned response would be very ineffective indeed; think about the need to find food to survive, for example: say we are primitive creatures in the jungle and you by pure chance taste a banana. The banana tastes good, but if you were just conditioned to remember that it tasted good—and not to the smell, the shape, the color, or the location of the banana—your ability to find it again would be impaired. Once you create this conditioned memory, though, it’s just like Pavlov’s dogs; the response becomes a reflex. This conditioned response underlies both the drive in drug addiction and the drive in compulsive eating.
What’s going on in the brain during cravings?
Had Pavlov been able to see inside the dog’s brain, he would have very likely seen that there is an increase in dopamine in the brains of those dogs when they get exposed to the sound previously paired with the meat. Dopamine tells us what's important—the unexpected bits of new information we need to pay attention to in order to survive, like alerts about sex, food and pleasure, as well as danger and pain. Indeed we’ve tested these in humans using brain imaging technologies. The human brain is highly sensitive to food stimuli. We’ve documented that when you show people favorite foods, to which they’ve been conditioned, there is an increase in dopamine in the striatum which is a brain region involved with reward and behavioral motivation. Mind you, this increase is just from smelling and looking at the food, because we tell study participants that they will not be able to eat it. And this is the very same neurochemical response that happens when addicts see a video of other people taking drugs, or anything to do with their drug of choice, like where they normally take it or with whom they take it.
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Also in the brains of both drug addicts and obese people we typically find a reduced number of D2 dopamine receptors in the striatum, compared to non-abusers and non-obese controls, respectively. Perhaps these findings reveal that the brain is somehow trying to compensate for the repeated surges inn dopamine stimulation from continuous stimulation with drugs or food. Another possibility is that these individuals had lower numbers of receptors to begin with, a biological feature that may put them at increased risk for diseases of addiction, in general. Low numbers of D2 receptors are well documented in people addicted to cocaine, alcohol, opiates and other drugs. Interestingly, a study by Dr. Gene Jack Wang and colleagues found the same type of relationship between the availability of D2 receptors and Body Mass Index (BMI) in obese individuals. In other words, the more obese a person is, the fewer receptors they have. By contrast, in normal weight subjects, the levels of D2 receptors are not associated with their BMI.
Now the chronic use of drugs—by repeatedly stimulating the dopamine and other systems--eventually leads to a disruption of function in frontal cortical areas involved with inhibiting behaviours and emotions. It is also possible that this circuit is weaker in people who are addicted to drugs from the start, but we don’t know that yet. In obesity, however, we do not have evidence, to my knowledge, that the frontal cortex is similarly disrupted. What has been documented instead is that the drive for food is so powerful that it overrides any ability to exert inhibitory control.
Are particular foods more reinforcing than others? Why?
Yes, absolutely. High calorie foods—particularly foods that are high in fat or sugar—are more likely to trigger compulsive eating. Again, that makes sense from nature’s perspective. As hunters, we didn’t always succeed at finding something to eat and so high-calorie foods, which pack a lot of energy, offered a survival advantage. In that environment, it was in our best interest to consume as much of this type of food as we could find. So they are very reinforcing. But today when we open up our refrigerators, we have a 100 percent chance of succeeding at finding food.
Our genes have changed little, but in our environment, we are now surrounded by high-fat, high-sugar foods. And this abundance is undoubtedly a major factor contributing to the rise in obesity Conditioning responses are incredibly powerful with food: when I go past a vending machine and I see chocolates I like very much, I desire the chocolate even though I’m not hungry. But if those chocolates weren’t there, it would be the last thing on my mind.
Are certain people at greater risk for drug or food addictions?
We know from twin studies that approximately 50 percent of the risk for both addiction and obesity is genetic. But the genes involved come into play on many different levels—from differences in the efficiency with which we metabolize drugs (or food) to differences in our likelihood of engaging in risk-taking or exploratory behaviors to more specific risks, such as the underlying sensitivity of the reward system.
In obesity, some people may be at a greater risk for compulsive eating because they may be overly sensitive to the rewarding properties of food. One study showed that some obese people have increased brain activity in response to mouth, lip and tongue sensations. For them, eating may be much more pleasurable than other natural reinforcers. Likewise, some people are not very efficient at registering or responding to internal signals of satiety, so they are possibly going to be more vulnerable to cravings triggered by food cues in their environment.
For example, in a recent study we looked at obese people who had an Implantable Gastric Stimulator (IGS), which electrically activates the vagus nerve and causes the stomach to expand and feel full. And even with this implant, these people still only manage to lose about five percent of their body weight. On a higher level, they have powerful conditioned responses that can apparently override other regulating signals
Does the overlap between addiction and obesity reveal any new targets for treatment?
There are pharmacological interventions to explore, such as medications that increase the dopamine response in the brain. Rimonabant, which boosts dopamine levels by dampening the endocannabinoid system, has shown promise in helping people who are obese and those who are smokers.
Another exciting development is the recent synthesis and preliminary testing of an orally administered drug that blocks orexin, a peptide that reinforces the “high” associated with drinking alcohol and is thought to regulate feeding. This drug could be extremely helpful in the treatment of specific brain disorders that involve aberrant food and drug taking behaviors. Also, because of the stigma associated with both of these conditions, obesity and drug addiction can lead to a deep sense of isolation, which is very stressful. This is an area where group therapy could help.
Yet another exciting area NIDA is researching is the use of functional magnetic resonance imaging (or fMRI) in biofeedback to train people to exercise specific parts of their brains, just like muscles. Sean Mackey of Stanford University, neuroscientist Christopher De Charms of Omneuron [in SanFrancisco] and their colleagues have similarly trained healthy subjects and chronic-pain sufferers to control their brain activity to actually modulate their experience of pain. So NIDA is exploring the possibility that you might use this kind of biofeedback to train people to control a region of the brain called the insula, which has been implicated in food and drug cravings. Smokers who have a lesion in the insula after a stroke, for instance, seem to lose the desire to smoke.
But one of the major and distinct obstacles for a person trying to recover from compulsive eating is the obvious fact that you have to eat in order to survive whereas, if you are addicted to an illegal substance, you are in a way protected by the fact that that drug is not going to be environmentally available everywhere. One of the therapeutic interventions for drug addicts is to teach them to avoid places associated with their habit. But how do you do that with food? It’s impossible.
And these people suffer. In rats, it has been shown that, if you give them very high-sugar diets and then make them give them an opioid antagonist (naloxone), you can trigger a withdrawal that is similar to that you observe when you give naloxone to an animal that has received repeated injections of morphinel. This indicated that chronic exposure to high sugar diets generated physical dependence. If similar processes happen in humans then interventions to mitigate the appearance of withdrawal symptoms during dieting may benefit the discomfort to the subject and improve outcomes.
Addiction is not a choice. It is a reflexive response. Do you think that Pavlov’s dogs had a choice of salivating when they heard the sound that had been conditioned to the meat? They did not and had you seen inside their brains you would probably have observed that the sound would trigger dopamine increases in their striatum that would be signalling to expect the reward of the meat. The message that you get when dopamine is liberated in striatum—in this case, the dorsal striatum—is that you need to get into action to achieve a certain goal. It is a powerful motivator. It is extremely hard to overcome these impulses with sheer willpower.
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DOR BioPharma, Inc., Is The Only Company In The World Able To Produce A Ricin Vaccine In Scale That Meets The FDA' S GMP Standards
08 Sep 2007
http://www.medicalnewstoday.com/articles/81812.php
the undervaluation of this stock is insane
Ricin toxin is a bioterror threat that is extremely deadly in small doses and can lead to lung damage and general organ failure leading to death within several days. Evidence is mounting that al Qaeda is experimenting with manufacturing ricin for the purposes of using it as a bioterror weapon. There are currently no vaccines available to prevent ricin poisoning or medical treatments to care for poisoning victims. Ricin can be easily produced, is stable over long periods of time, is toxic by several routes of exposure and thus has the potential to be used as a biological weapon against military and civilian targets.
DOR BioPharma, Inc. (OTC BB: DORB) has developed a proprietary vaccine, RiVax™, to protect against exposure to ricin toxin. RiVax™ is the first ricin toxin vaccine ever to be clinically tested in humans. DOR's ricin vaccine development program, through University of Texas Southwestern, is led by the world-renowned Ellen Vitetta, PhD, Director of the Cancer Immunobiology Center at University of Texas Southwestern Medical Center at Dallas (UT Southwestern).
According to the Center for Disease Control and Prevention, threats to U.S. citizens are categorized by threat level. Category A consists of agents that are easily disseminated and may cause the highest mortality, category B includes those agents that are easily disseminated and can cause moderate morbidity and low mortality include, while category C includes agents that contain emerging pathogens with potential for high morbidity and mortality. Until recently, ricin has been categorized as a B-level threat. Recent results from additional animal testing of RiVax™ at the University of Texas Southwestern Medical Center "…indicates pure ricin toxin is 2000 fold more toxic by the oral route than previously described," said Ellen Vitetta, PhD, Director of the Cancer Immunobiology Center at UT Southwestern. These developments will likely shift ricin from threat level B to threat level A.
DOR has announced positive Phase I clinical trial results for RiVax™ which demonstrated that the vaccine is well tolerated and induces antibodies in humans that neutralize the ricin toxin. 15 volunteer participants were administered RiVax™ in rising doses over a 1.5 year period. The trial resulted with the desired end point of "Safety" met.
The vaccine can induce protection against mortality and tissue damage from both aerosol and oral toxin exposure; the most likely routes to be used in a ricin toxin biological attack.
DOR is the only company in the world able to manufacture a ricin vaccine in scale (in large quantities easily) and meet the FDA's Good Manufacturing Practice (GMP) guidelines which requires documentation of every aspect of the process activities operations involved with drug and medical device manufacture. GMP requires that all manufacturing and testing equipment has been qualified as suitable for use, and that all operational methodologies and procedures (such as manufacturing, cleaning, and analytical testing) utilized in the drug manufacturing process have been validated (according to predetermined specifications), to demonstrate that they can perform their purported functions.)
http://www.dorbiopharma.com
DOR BioPharma, Inc., Is The Only Company In The World Able To Produce A Ricin Vaccine In Scale That Meets The FDA' S GMP Standards
08 Sep 2007
http://www.medicalnewstoday.com/articles/81812.php
Ricin toxin is a bioterror threat that is extremely deadly in small doses and can lead to lung damage and general organ failure leading to death within several days. Evidence is mounting that al Qaeda is experimenting with manufacturing ricin for the purposes of using it as a bioterror weapon. There are currently no vaccines available to prevent ricin poisoning or medical treatments to care for poisoning victims. Ricin can be easily produced, is stable over long periods of time, is toxic by several routes of exposure and thus has the potential to be used as a biological weapon against military and civilian targets.
DOR BioPharma, Inc. (OTC BB: DORB) has developed a proprietary vaccine, RiVax™, to protect against exposure to ricin toxin. RiVax™ is the first ricin toxin vaccine ever to be clinically tested in humans. DOR's ricin vaccine development program, through University of Texas Southwestern, is led by the world-renowned Ellen Vitetta, PhD, Director of the Cancer Immunobiology Center at University of Texas Southwestern Medical Center at Dallas (UT Southwestern).
According to the Center for Disease Control and Prevention, threats to U.S. citizens are categorized by threat level. Category A consists of agents that are easily disseminated and may cause the highest mortality, category B includes those agents that are easily disseminated and can cause moderate morbidity and low mortality include, while category C includes agents that contain emerging pathogens with potential for high morbidity and mortality. Until recently, ricin has been categorized as a B-level threat. Recent results from additional animal testing of RiVax™ at the University of Texas Southwestern Medical Center "…indicates pure ricin toxin is 2000 fold more toxic by the oral route than previously described," said Ellen Vitetta, PhD, Director of the Cancer Immunobiology Center at UT Southwestern. These developments will likely shift ricin from threat level B to threat level A.
DOR has announced positive Phase I clinical trial results for RiVax™ which demonstrated that the vaccine is well tolerated and induces antibodies in humans that neutralize the ricin toxin. 15 volunteer participants were administered RiVax™ in rising doses over a 1.5 year period. The trial resulted with the desired end point of "Safety" met.
The vaccine can induce protection against mortality and tissue damage from both aerosol and oral toxin exposure; the most likely routes to be used in a ricin toxin biological attack.
DOR is the only company in the world able to manufacture a ricin vaccine in scale (in large quantities easily) and meet the FDA's Good Manufacturing Practice (GMP) guidelines which requires documentation of every aspect of the process activities operations involved with drug and medical device manufacture. GMP requires that all manufacturing and testing equipment has been qualified as suitable for use, and that all operational methodologies and procedures (such as manufacturing, cleaning, and analytical testing) utilized in the drug manufacturing process have been validated (according to predetermined specifications), to demonstrate that they can perform their purported functions.)
http://www.dorbiopharma.com
Cialis boosts sex after spinal cord injuries: study
I just keep having sex without the spinal cord injury, thank you.
Jav followers
you guys talk about how high reimburesment will be because of the cost savings. Just because it saves the Europeans money doesn't mean they will pass the savings on to the company.
they will pay as little as they can, and Javelin will have to take it up the Kuzoo just like the other pharma companies selling drugs in Europe do.