This is not the final word on bapi, however. This study is actually the first of four placebo-controlled, Phase III trials to be completed. Other studies of patients who are ApoE4 carriers and non-carriers are under way. Topline results from another study in patients with mild-to-moderate Alzheimer’s disease who do not carry the ApoE4 genotype are expected to be announced later this summer.
“While we are disappointed in the topline results of Study 302, a more complete understanding of bapineuzumab and its potential utility in mild-to-moderate Alzheimer’s disease will be gained following the availability of additional data, including data from the soon-to-be available non-carrier Study 301,” says Steven Romano, senior vp atnd head of the Medicines Development Group, Global Primary Care Business Unit at Pfizer (in a statement).
The results did not elicit much surprise. "Recall that the odds of success in these carriers might be lower than in the non-carriers (at least this appears the case based on the Phase II data)," ISI Group analyst Mark Schoenebaum wrote in an investor notes. "Data for the second trial will be out soon – this second trial is done in non-ApoE4 carriers and may have a somewhat higher probability of success."
Why such a reaction? Three years ago, the drug failed to achieve statistical significance and also raised the risk of a potentially serious side effect, especially in people with a genetic risk of developing Alzheimer’s. Twelve people developed a build-up of fluid in the brain called vasogenic edema. And 10 of those cases were in people who have the ApoE4 gene, which significantly raises their risk of developing Alzheimer’s (back story).
Nonetheless, there has been significant interest in bapi, which is being developed by Pfizer, Johnson & Johnson and Elan, if only because positive results would amount to a huge win, both medically and financially. Alzheimer's has proven to be a persistently difficult ailment to combat, though, and for this reason, a recent survey of 146 institutional investors gave, on average, 21 percent probability that bapineuzumab will hit all primary endpoints. Similarly, just 14 percent gave solanezumab, which is being developed by Eli Lilly, a chance of meeting its study goals (see this).
In an investor note, Sanford Bernstein analyst Tim Anderson pointed out that "the lack of release of top-line results should not be inferred as the trial having shown efficacy... successful (drugs) for this ailment could be the next Lipitors – in terms of their size - should they work and we have pegged the probability of success at around 20 percent for the category as a whole. These initial results will, naturally, make investors more skeptical than they already are, yet as mentioned, the odds of success are presumably higher in non-carrier AD patients."
Data from both the ApoE4 carrier (Study 302) and non-carrier (Study 301) studies will be presented in September at the European Federation of Neurological Societies meeting in Stockholm.
brain pic thx to tocaboca on flickr