p3analyze:
Unfortunately, it seems that what many biotech execs fail to tell their shareholders winds up being the most important things. D Miller may be a nice guy and a decent analyst, but if anything, rather than interrogating Gold as to why DNDN failed to disclose their preapproval inspection failure to shareholders when it occurred in mid February, he seems to offer excuses for it, in spite of the fact that even he doesn't know what those deficiencies were. He might also have asked why DNDN was surprised to receive the Complete Response Letter for Provenge in May despite those known manufacturing problems and the absence of labeling discussions in April while Gold and two directors were selling millions in DNDN shares. Then again, he needn't bother now since those issues may be resolved by a Federal Court in Seattle within the next two months.
IMO, the FDA will eventually approve both Provenge and GVAX for use in AIPC, but there is obviously some very useful information that DNDN and CEGE are keeping close to their vests that they don't necessarily have a legal duty to disclose. Statistically, for example, CEGE recently indicated that the Vital 1 trial passed its interim look and will continue to its final look when 400 events have occurred, now projected to occur in 2H09. When CEGE reached their Vital 1 interim point in January, they also disclosed that Vital 1 used the very conservative O'Brien Fleming method of allocating its alpha at the interim, which was estimated to be a p value as low as 0.003. The number of interim events in Vital 1 was said to be 200. Prior knowledge of those constraints especially when comparing a relatively fast acting cytotoxic against a delayed action immunotherapy would have set the Vital 1 interim up as a non event in advance, except perhaps to assure that the GVAX treated patients weren’t dying faster than the Taxotere treated patients.
WRT DNDN, estimates as to what the allocated alpha might be in 9902b needed to supply the FDA with the required additional efficacy data and restart the Provenge PDUFA clock vary widely, as do estimates as to the number of events required for the interim look (180?, 240?), which DNDN projects will occur in mid 2H09. All DNDN has said is that the number of events will be more than the 164 recorded at the 3 year mark in 9901 and 9902a. Success or failure at the 9902b interim will have an enormous impact on the market cap of DNDN and any ability to have a significant lead over CEGE’s GVAX in introducing the first FDA approved immunotherapy in AIPC. It’s safe to say that a very conservative interim allocated alpha combined with a low number of events would substantially reduce the probability of success at the interim as compared to a high alpha and larger number of events. DNDN should know these numbers, but has not disclosed them.
The other topic, which was obviously sensitive for CEGE yesterday, and may be for DNDN, is the permissive use of subsequent Taxotere after GVAX in Vital 1 and after Provenge in 9902b. DNDN finessed this subject in the Briefing Materials for the AC by reporting that a slightly higher percentage of the control group in 9901 had received subsequent Taxotere, suggesting that the overall increase in median survival, therefore, did not disproportionately favor the Provenge experimental arm. CEGE’s CEO stated that there should be sufficient Vital 1 subgroup data to compare those who take GVAX alone vs, those who take the combination. The issue may have more to do with marketing than medicine, however, since the analysis by Dr. Petrylak suggests that the combination of Provenge with subsequent Taxotere is clearly and substantially superior to Provenge alone. However, many more asymptomatic AIPC patients might elect to take Medicare reimbursed Provenge or GVAX with their relatively mild side effects without committing to the rigors of Taxotere if either or both therapies are approved as substantially effective standalone therapies and the disproportionate beneficial contribution of the combination therapy on reported composite survival inclusive of immunotherapy alone is not highlighted in labeling.
IMO, biotech history strongly suggests an inverse relationship between the level of management hype and non disclosure and the problems that any therapy seeking FDA approval encounters. There is also a likely inverse relationship between biotech investor gullibility and investor net worth. The whole FDA approval process, and the patients and investors who depend on the process, could greatly benefit from FDA transparency and public reporting on progress or problems encountered in each application. JMHO.
