Phase II clinical trials of anti–amyloid β antibodies: When is enough, enough?

Efforts to develop new therapies to combat Alzheimer's disease suffer from extraordinarily high failure rates that make it difficult to justify continued investment in the field. Although there are a number of plausible explanations for this extremely high attrition rate, one of the explanations that has received little attention is the lack of compelling data from Phase II studies for compounds that have been pushed into Phase III trials and then have failed. An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. The published data suggest that sponsors took decisions to move these compounds into Phase III on the basis of vastly limited data that were rife with type I error and probably driven by commercial concerns. The continued push to move compounds that are not likely to succeed in later stage clinical trials threatens to erode trust in the clinical research enterprise making it much harder to properly test truly promising compounds.