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Re: io_io post# 275

Sunday, 04/22/2007 5:02:04 PM

Sunday, April 22, 2007 5:02:04 PM

Feuerstein's Biotech Mailbag re DORB
By Adam Feuerstein
Senior Writer
4/21/2007 10:48 AM EDT
URL: http://www.thestreet.com/newsanalysis/biotech/10351640.html

with my adjustments, if that is okay

Welcome back to the Biotech Mailbag, where this week, thankfully, we won't be talking about Dendreon (DNDN) (directly, at least, as you'll see below). But a Dendreon-free mailbag can still be fun and informative, right? Remember to email me here.

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Mike W. writes, "What is your opinion on DORB? Will OrBec be approved?"

Mike is referring to minuscule market-capped DOR BioPharma (DORB) and its drug OrBec, which goes in front of the Oncologic Drug Advisory Committee of the Food and Drug Administration on May 9.

I've actually received a bunch of email about DOR since the Dendreon advisory panel last month because there are similarities between the two companies. DOR is seeking FDA approval of OrBec, a cancer-related drug, based on a clinical trial that failed its primary endpoint but which later showed that OrBec patients were living longer.

The statistics supporting this survival benefit are controversial, and it will be up to an advisory panel of experts to hash it all out and offer a recommendation to the FDA.

Is this Dendreon déjà vu, or what? Yes and no. There is at least one significant difference of which you should be aware (and wary).

OrBec is an oral (pill) reformulation of a well-known topical steroid that aims to treat the gastrointestinal aspects of graft-versus-host disease, or GVHD, in cancer patients who have undergone bone marrow transplant. In GVHD, immune cells from the donated bone marrow attack the recipient's organs and tissue -- most often in the GI tract. There are no approved drugs to treat GVHD, although steroids and other immunosuppressants are often used.

DOR and its researchers believed that daily use of OrBec, which can specifically target GVHD in the gut, would allow patients to use a much shorter course of prednisone, an injectable steroid commonly used to treat GVHD but which brings with it a lot of toxicity and side effects. If OrBec allowed patients to taper off prednisone faster, it would be a safer treatment for patients while still keeping GVHD at bay.

Well, DOR ran a phase III trial to test this hypothesis and it failed the primary endpoint. At Day 50, OrBec patients had a 31% cumulative rate of GVHD treatment failure compared to 48% for placebo patients. While this result trended in favor of OrBec, the result was not statistically significant.

the trend of that endpoint was .0513

The treatment failure rate at 80 days was 39% for orbec vs. 65% for the placebo with a p value of .0048. this was not data mining, this is a pre defined endpoint.

But when these patients were followed for longer periods of time, the OrBec patients were found to be living longer than patients taking a placebo. At 200 days after bone marrow transplant, five OrBec patients were dead compared to 16 placebo deaths -- a 67% reduction in the risk of death. This survival benefit was durable out to one year after transplant.

In January, I spoke with the primary investigator in the OrBec trial, Dr. David Hockenberry of the Fred Hutchinson Cancer Research Center. The study had just been published in the medical journal Blood, and DOR was eager to get the word out about its drug.

Hockenberry acknowledged the difficulty in reconciling the conflicting data coming from the trial. In hindsight, 50-day GVHD treatment failure was not an ideal primary endpoint, he said, but then, the survival benefit was a positive surprise and one the researchers had difficulty explaining away. Of course, statistics become an issue because there was no retrospective plan to analyze the trial for survival.I don't understand this comment because they didn't need a retrospective plan to analyse survival because they had a prospective plan to analyse it. Survival was a secondary endpoint. Is Orbec really boosting survival in these patients, or is some other, outside factor the positive contributor?

One thing that the panel can't claim is that the healthier patients were orbec group. The orbec arm had the sicker patients.
The mechanism of action which the panel members should be familiar with is graft vs. tumor. The predisone reduces this effect.

This is the central question that the Oncologic Drugs Advisory Committee will grapple with on May 9.

A tremendous difference between orBec and Provenge data is that orbec had consistent reductions in GVHD treatment failure across two trials;
a.consistent reductions in prednisone exposure across two trials;
b.consistent reductions in mortality at 200 days post-transplant across two trials;
c.consistent reductions in mortality at 1 year post-randomization across two trials;

Provenge only showed its benefit on a retrospective analysis in one trial.

It's Dendreon-esque, except for the fact that ODAC is likely to be much tougher than the gene therapy panel that reviewed Provenge for Dendreon. This could be a big problem for DOR.

Except for the fact that orbec works I am not convinced that Provenge does.

just as important in today’s regulatory environment, beclomethasone dipropionate (orBec) is a well understood marketed chemical that has been demonstrated for over 20 years to be safe (unlike Provenge), and has continued to be true and consistent with the clinical safety data in GVHD.

The FDA is expected to issue an approval decision on OrBec on or before July 21.

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