As the G7 populations continue to age, most notably the greying U.S. baby boomer generation, the prevalence of Alzheimer's disease (AD) is expected to increase significantly. By 2021, more than 10 million people across the G7 will be living with AD while nearly 5 million more can expect to begin developing clinically evident symptoms within 1 to 2 years. Despite a large and growing patient population, the cause of AD is still poorly understood and currently available treatments offer limited efficacy. However, this past year has seen both notable advances?as well as setbacks?in AD drug development.
The beta-amyloid (A?) cascade has been a major therapeutic target of the pharmaceutical industry for over a decade. In particular, the anti-A? monoclonal antibody (MAb) bapineuzumab, co-developed by Janssen Alzheimer Immunotherapy and Pfizer, had garnered quite a bit of attention in the past few years. The drug's failure in Phase III trials this August was a disappointment to the AD community and underscored the challenges faced by drug developers when choosing to advance a compound into Phase III trials on the basis of post-hoc analyses of Phase II data.
Eli Lilly also reported data from two, large-scale Phase III trials anti-A? MAb solanezumab this year. While data from the individual trials was somewhat lackluster, the pooled data from the two studies showed the drug had modest therapeutic efficacy in mild AD patients. Considering the recent slew of late-stage failures, this success can be considered a partial victory for the field. Following discussions with the FDA about the path forward for solanezumab's development, Eli Lilly announced plans for an additional Phase III study of the agent in mild AD patients.
The past year also saw the initiation of the first prevention trials for AD, including the Alzheimer's Prevention Initiative (API) trial, the Dominantly Inherited Alzheimer's Network (DIAN) trial, and the Anti-Amyloid in Asymptomatic Alzheimer's (A4) Trial. Additionally, studies in prodromal AD patients have begun recently, most notably the Scarlet Road trial of Roche's anti-A? MAb gantenerumab. Thought leaders have increasingly voiced the opinion that such early trials will prove vital to furthering our understanding of AD, and are optimistic that the ongoing efforts will yield valuable data and, ultimately, effective therapies.
Despite a number of recent setbacks in the field, we are still optimistic about the long-term AD pipeline, thanks in part to development of novel BACE inhibitors, anti-A? MAbs, novel symptomatic therapies and the further development of solanezumab. Additionally, with the jury still out on the amyloid hypothesis, we expect the field to broaden its focus to include therapies acting on other potential pathways such as tau in addition to A?.
Joseph Martinez is an Associate with the DRG Consulting group.
Georgiana L. Kuhlmann, S.M. is a research analyst with Decision Resources.
Decision Resources Pharmacor, 2012: Alzheimer's Disease (Event Driven)