Approval of Aducanumab may provide a proof of concept upon which to rapidly improve

The recent US Food and Drug Administration (FDA) approval of aducanumab – which has the potential to treat Alzheimer’s disease – may provide a proof of concept that can be rapidly improved upon, writes Dennis Selkoe in this Perspective. It may also enable combination treatments, as is typical in chronic diseases. “In therapeutics, as in life, one must walk before one can run,” he says. Few recent trials of potential Alzheimer disease (AD)-modifying agents appear to have met their primary endpoints. The clearest evidence of disease modification so far has come from secondary biomarker endpoints, principally a substantial decrease in amyloid plaques in the brain over 18 months. This occurred in the two phase 3 trials of aducanumab, an amyloid β (Aβ) monoclonal antibody that was approved by the FDA in June 2021. This led to some controversy. This controversy should be considered in the context of other recent AD immunotherapy trials, Selkoe says, highlighting 3 other antibodies against amyloid β that have shown they can clear amyloid deposits from the brain in phase 2 or 3 trials. Collectively, these data represent the closest the AD field has come to a disease-modifying approach, Selkoe says. And while the cognitive benefits of these potential AD-modifying agents are modest, and the challenge of assessing their clinical meaningfulness remains, this challenge has been experienced in other chronic diseases. “For many chronic diseases, the initial therapeutic compounds have limited efficacy and are often steadily replaced by more effective drugs…Gaining real-world experience with a first, albeit modest, treatment should encourage development of more potent second-generation agents,” Selkoe says. He does name challenges to physicians who may consider using aducanumab for patients. He also highlights the drug’s high price. “These and other challenges in the march to implement the first approved AD therapeutic require thoughtful planning and resourcefulness,” Selkoe writes, “but this is just the process that patients and caregivers have long awaited.”