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Biotech / Medical : IPIC -- Ignore unavailable to you. Want to Upgrade?

To: Grainne who wrote (1190)	4/23/1998 12:07:00 PM
From: NeuroInvestment	Read Replies (1) \| Respond to of 1359

I just posted this subsection of an interim communication sent to subscribers. I apologize that, since they have not all received it yet, that the section pertaining most directly to the second question is not included. In response to the first; fast track approval has to do inherently with the nature of the disorder and need for treatment, it does not have to involve imputation of efficacy. In this case however, the FDA was well acquainted with the previous Phase IIIs. No one, IPIC or the FDA, would have expected this MRI study result. The comments below pertain to the aftermath. NeuroInvestment (www.neuroinv.com) INTERIM COMMENT: Interneuron/CerAxonApril 1998 Rather than wait for the May issue, the stunning negative developments for Interneuron's CerAxon warranted immediate response and comment: 1) The failure of the CerAxon MRI Study, which was intended as a supplemental Phase III, was primarily ( we do not know if any other factors may have been contributory) due to an as-yet unexplained (the analyses have not been completed) rate of spontaneous improvement in the placebo group; they showed a degree of shrinkage in the size of their infarcts approximately double that which would have been expected based on previous stroke research. Whether there was some imbalance in the drug vs. placebo groups is yet to be determined, but with only 87 evaluable patients (13 of the original 100 died during the study), there was no room for error, any skew would throw off the results. Given the small size of the sample, no significant change in NIHSS results would have been expected. If the drug had any effect, it was invisible in comparison to this placebo effect. In our view, these results reflect trial design failure, not drug failure. 2) Interneuron must take some blame for having constructed a study with such a small sample size, overly vulnerable to the vagaries that plague human trials. MRI trials are admittedly expensive, and originally this was to be simply supplemental, not so as overwhelmingly 'pivotal' as it turned out to be. In the end, it was an underpowered Phase III that torpedoed the filed NDA. It also overrelied on estimates of MRI measured-infarct changes that reflect a limited database. 3) The FDA must also take much blame. The FDA overweighted the results of this 87 patient study, and made it clear that it would reject the NDA if not withdrawn; Interneuron had no choice. Thus, the positive results obtained from the three other Phase III studies, involving a total of almost 800 patients, have been dismissed by the FDA based on this 87 patient trial. This is perverse prioritization, and reflects the fact that the FDA continues to be more concerned with statistical detail than patient welfare. A reasonable response to the failure of this small trial would have been approval with mandated Phase IV studies (i.e. compared to historical controls). Based on the results of the large Phase III trials previously conducted, we believe that CerAxon's delay (15-18 months) means that 50,000-100,000 Americans who suffer strokes over that time will end up with permanent disability that would have been prevented had CerAxon been available. It is decision-making like this that clarifies one chilling point; FDA 'Reform' is more sham than substance thus far. 4) CerAxon is not dead, and Interneuron had already laid the groundwork for a 700 (or more) patient study. Dosing may be changed to maximize the likelihood of positive response (1000mg orally is the standard of care in Europe), IV administration (as is used in Japan) is much less likely.