Pfizer/Johnson & Johnson: discontinuation of IV bapineuzumab places solanezumab under scrutiny.
Pfizer/Johnson & Johnson: discontinuation of IV bapineuzumab places solanezumab under scrutiny
Having failed to meet its co-primary endpoints in the second of four Phase III trials, development of IV bapineuzumab in Alzheimer’s disease has been abandoned. Discontinuation of this eagerly anticipated candidate will reignite debate surrounding the appropriateness of targeting beta amyloid in cases where plaques are already present, and shine the spotlight firmly on Eli Lilly’s solanezumab.
The decision to discontinue development of bapineuzumab intravenous (IV) in mild to moderate Alzheimer’s disease was based on co-primary clinical endpoints not being met in two Phase III studies. According to top-line results of Study 301, announced on August 6, bapineuzumab IV failed to show any impact on cognitive or functional performance compared to placebo in patients with mild to moderate Alzheimer’s disease who do not carry the ApoE4 genotype. This followed the July 23 announcement that a Phase III trial (Study 302) of IV bapineuzumab in ApoE4 carriers – who tend to have a higher risk of developing Alzheimer’s earlier – also failed to meet its co-primary endpoints.
Currently available treatments for Alzheimer’s disease have only symptomatic modes of action. As such, bapineuzumab’s passive immunization against beta amyloid and its disease-modifying potential had positioned it as one of the most eagerly anticipated developmental drugs for the estimated 7 million patients with Alzheimer’s disease across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK). Indeed, with Pfizer and Johnson & Johnson previously leading the race to launch the first beta-amyloid antibody for mild to moderate Alzheimer’s disease, the failure of a second high profile clinical trial comes as a considerable blow to both companies.
Bapineuzumab’s discontinuation provides fresh evidence that targeting amyloid in Alzheimer’s disease may not be an appropriate treatment option in cases where the plaques are already in evidence. This may prompt developers of amyloid-based approaches to interrupt the pathway at an earlier stage, prior to plaque formation. Nevertheless, Pfizer and Johnson & Johnson maintain that beta amyloid remains a promising path to potential clinical benefits for patients with Alzheimer’s disease, with a Phase II study of a subcutaneous formulation of the drug set to continue. However, at this time, the companies have no plans to study bapineuzumab in asymptomatic patients or those at an earlier stage of the disease.
Bapineuzumab’s discontinuation places Eli Lilly’s solanezumab under increasing scrutiny ahead of the announcement of highly anticipated Phase III study results. Like bapineuzumab, solanezumab targets the beta-amyloid pathway and holds disease-modifying potential in Alzheimer’s disease. With bapineuzmab’s departure from the race likely to decrease confidence in solanezumab’s demonstrating efficacy, the absence of new safety concerns in bapinezumab’s Phase III trials will be of little comfort to Eli Lilly. Should solanezumab also fail its primary efficacy endpoints, Datamonitor expects that research efforts will increasingly shift towards interventions at an earlier stage of the disease.