The topline results of the first bapineuzumab Phase III to report came out today, and to the surprise of no one that we know, they were negative. This trial was in APOE4 carriers, the next Phase III trial to report will be in noncarriers. The expectations for that trial, and the two other Phase IIIs, are similarly low, though there are some who hope the non-carriers will be more responsive. If the patients enrolled in the noncarrier trial were in fact earlier in the ‘mild-to-moderate’ range than were these patients, perhaps there is some glimmer of possibility there, in that there may have been less pathology already in process.That’s not where we would be parking our hopes and dreams. It is a reminder that ‘Phase IIb is not optional’, and no one should ever embark on such a massively expensive Phase III production without first going through a smaller-scale rehearsal.
But this should also be a reminder that these ‘home run’ shots are not the only way to make a meaningful difference in Alzheimer’s. One does not need to cure the disease to make life far more independent and meaningful for patients–and their families. So as a reminder, Lundbeck‘s Lu58054 produced significant cognitive improvement as an adjunct to Aricept, and perhaps even more importantly (as was discussed in the prior post on this blog), EnVivo‘s EVP-6124 produced impressive cognitive and functional benefit as both adjunct and monotherapy, and its Phase IIb data suggested the possibility that it may have been disease-modifying as well. If Bapi’s coming data confirms the bad news from this trial, that will by no means prove that all approaches are fruitless, it will instead show that downstream tactics may be a more pragmatic and approachable route than tackling AD at its pathophysiological roots.