Lessons Learned From Aducanumab Experience and Antiamyloid Therapies: Ian Kremer

WATCH TIME: 8 minutes

"CMS (Centers for Medicare & Medicaid) institutionally needs to respect the existence of accelerated approval. And the FDA needs to remain confident that if it issues an accelerated approval that it will mean coverage by CMS for those products, or otherwise, it’s a futile exercise for the FDA to even have accelerated approval. [Otherwise] we can throw away progress for generations of people across disease spectrums, not just people with Alzheimer."

In late January, Biogen announced it would discontinue the development and commercialization of aducanumab (Aduhelm) and its confirmatory phase 4 ENVISION study in efforts to reallocate funds to other Alzheimer disease (AD) drugs in its pipeline.¹ Aducanumab, an antiamyloid therapy, was the first of its kind approved under the accelerated approval pathway in June 2021.

The therapy’s approval path was unique and controversial. In its late-state development program, which consisted of 2 phase 3 trials, 1 met its primary end point and 1 did not. Despite the differing results, the FDA went on to approve the agent as the first AD treatment since 2003, suggesting aducanumab “consistently and very convincingly” reduced amyloid plaques in both a dose- and time-dependent fashion.² Following its approval, Biogen was required to conduct phase 4 studies to confirm the benefit of the drug; however, several of them failed to launch, namely because of issues with insurance coverage and funding.

Years later, the FDA approved lecanemab (Leqembi; Eisai), the second antiamyloid drug of its class, for patients with early-stage AD. After originally receiving an accelerated approval, it was transitioned to a traditional approval months later, in July 2023.³

Several in the field were displeased by the process by which aducanumab was approved; however, some feel as though it was a step of progress towards the next generation of therapeutics. To gather some thoughts on the journey of aducanumab and the lessons learned since its approval, NeurologyLive^® sat down with Ian Kremer, executive director of the Leaders Engaged on Alzheimer’s Disease (LEAD) Coalition. Kremer provided perspective on the significance of the approval, its impact on future therapies, and where things went wrong. Furthermore, he gave thoughts on the issues with accelerated approval and the lack of coverage for therapies in this pathway, as well as why pharmaceutical companies and agencies like the FDA owe it to patients and community members to finish out phase 4 studies.

REFERENCES
1. Biogen to realign resources for Alzheimer’s disease franchise. News release. Biogen. January 31, 2024. Accessed February 22, 2024. https://finance.yahoo.com/news/biogen-realign-resources-alzheimers-disease-123000872.html
2. FDA’s Decision to Approve New Treatment for Alzheimer’s Disease. FDA. June 7, 20121. Accessed February 22, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease
3. 1. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. FDA. News release. July 6, 2023. Accessed February 22, 2024. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval