Alzheimer’s mAb policies do not set precedent for accelerated approval, CMS’s former CMO says

Lee Fleisher on The BioCentury Show: Access restrictions for anti-amyloid mAbs such as Aduhelm were based on unusual circumstances

CMS’s controversial decision to restrict access to Alzheimer’s mAb treatments approved under FDA’s accelerated pathway was a unique case that is unlikely to set a precedent, former CMS CMO Lee Fleisher told BioCentury. “I do not think this will be repeated,” he said.

In an interview with The BioCentury Show, Fleisher also discussed the opportunities and risks for healthcare posed by AI, and the scientific and legislative steps that will be needed to make real the promise of blood-based multicancer detection technologies.

Fleisher, the founder of healthcare consulting firm Rubrum Advising, served as CMO when CMS formulated national coverage policies for Alzheimer’s mAbs. He emphasized that those policies should not be seen as a signal that Medicare will routinely limit access based on accelerated approvals.

Contrary to some news reports, CMS was not surprised by FDA’s accelerated approval of Aduhelm aducanumab from Biogen Inc. (NASDAQ:BIIB) and Eisai Co. Ltd. (Tokyo:4523), Fleisher said. The agency received requests for a coverage determination from stakeholders who were worried that in the absence of a national policy regional Medicare administrative contractors would take different approaches. This could cause unacceptable variations in access based on where a patient lives.

AHIP, a trade association representing health insurance companies, also pressed CMS for a national coverage policy that could guide Medicare Advantage providers.

CMS restricted access to Aduhelm aducanumab and other Alzheimer’s mAbs marketed under accelerated approvals because FDA approved a label for Aduhelm that was broader than the population studied in trials, those trials were lacked diversity, Fleisher said.

Controversy over the predictive value of reduction of amyloid, the surrogate endpoint used to support accelerated approval, also played a part in CMS’s decision to restrict access to anti-amyloid mAbs marketed under accelerated approval, Fleisher said. “We continue to see questions about what is truly the etiology of Alzheimer’s and whether this is an epiphenomenon or not.”

It is not difficult, however, to envision a repetition of these factors.

FDA routinely approves drugs for indications that are broader than the study population, and although the agency and sponsors are working to address the issue, it isn’t uncommon for trials to fall short of the goal of matching the ethnic and racial diversity of the U.S. population.

Controversy over surrogate endpoints for accelerated approval is also all too common.

Fleisher expressed the hope that FDA’s efforts to develop scientific consensus about surrogate endpoints will lead to closer alignment between accelerated approvals and CMS coverage decisions.

Another factor distinguishes Alzheimer’s mAbs from other therapies prescribed for the Medicare population: the potential cost to the U.S. healthcare system.

Biogen projected that at its launch price of $56,000 for a year’s treatment, Aduhelm aducanumab would absorb a quarter of the Medicare Part B budget and cost taxpayers more than NASA’s 2018 budget. The company cut the price to $28,000, and after approval of Leqembi lecanemab, pulled it off the market.

Based on the policy Fleisher helped put in place, CMS relaxed access restrictions on Leqembi when it received traditional approval. Uptake, however, has not approached the levels Biogen anticipated when Aduhelm and Leqembi were under development.

While cost did not dictate CMS’s coverage decision, the potential burden on Medicare did influence the decision to craft a national coverage policy, Fleisher said. “Price does not influence the decision for coverage,” he told BioCentury. “What is clear is that the burden as far as the population and the total cost does influence whether a national coverage analysis is opened and whether a decision is made.”