On November 6, 2020, the US Food and Drug Administration (FDA) advisory committee reviewed issues related to the efficacy and safety of aducanumab, a human IgG1 anti-Aβ monoclonal antibody specific for β-amyloid oligomers and fibrils implicated in the pathogenesis of Alzheimer’s disease. Given the importance of drug innovation for this common and often devastating disease, the abandonment of prior monoclonal antibodies targeting β-amyloid, and the clinical, regulatory, and market effects that approval of aducanumab could have, there has been significant interest in the development and regulatory review of aducanumab.
As compelling public testimony during the FDA’s advisory committee meeting made clear, Alzheimer’s disease poses a major burden on millions of people and their families, and there is an overwhelming demand for safe and effective new treatments. In light of this, the sponsor of aducanumab deserves recognition for a development program that included the design and conduct of 2 well-controlled, randomized, potentially pivotal trials that should be published in the peer-reviewed literature. However, considering that these efficacy trials were stopped for futility, there is no reason to favor the trial with the positive signal in 1 of 2 treatment groups over the trial with the negative outcome in both treatment groups, and there is no persuasive evidence to support approval of aducanumab at this time. Randomized trials should remain the primary means that regulators use to assess product efficacy, and that patients, physicians, and policy makers rely on, to have confidence in the safety and effectiveness of new therapeutics.
Accordingly, based on the extensive evidence presented, the advisory committee voted on the question of whether study 302, independent of study 301, provides “strong evidence that supports the effectiveness of aducanumab for the treatment of Alzheimer’s disease” as follows: 1 yes, 8 no, and 2 uncertain. The FDA will consider this recommendation against approval in its evaluation of aducanumab, and a decision on the drug application is expected by June. Research, research, research, again, we are focused on improving the quality of life for those living with Alzheimer’s disease. Although these studies had less than great results, we must keep trying!
Stay well, mask up, and stay tuned!