CMS's Former CMO: Alzheimer's mAb Policies Not a Precedent for Accelerated Approval
Key Insights
Former CMS CMO Lee Fleisher states that access restrictions for anti-amyloid (search) mAbs like Aduhelm were based on unique circumstances, unlikely to be repeated.
CMS restricted access due to a broader-than-studied label, lack of trial diversity, and controversy over amyloid (search) reduction's predictive value.
Fleisher hopes FDA's efforts to build consensus on surrogate endpoints will better align accelerated approvals with CMS coverage decisions.
Former CMS Chief Medical Officer Lee Fleisher asserts that the Centers for Medicare & Medicaid Services' (CMS) controversial decision to limit access to Alzheimer's monoclonal antibody (mAb) treatments, approved via the FDA's accelerated pathway, was a unique case and is unlikely to set a precedent. Fleisher, now founder of Rubrum Advising, emphasized that these policies should not be interpreted as a routine limitation of access based on accelerated approvals.
Factors Influencing CMS Decision
Fleisher clarified that CMS's decision regarding Aduhelm (aducanumab) from Biogen and Eisai was prompted by stakeholder concerns about inconsistent regional Medicare administrative contractor approaches. The agency also received pressure from AHIP, a health insurance trade association, for a national coverage policy to guide Medicare Advantage providers.
Access restrictions were imposed due to the FDA approving a broader label for Aduhelm than the population studied in trials, coupled with a lack of diversity within those trials. The controversy surrounding the predictive value of amyloid (search) reduction, the surrogate endpoint used for accelerated approval, further influenced CMS's decision. Fleisher noted ongoing questions about the true etiology of Alzheimer's and whether amyloid reduction is merely an epiphenomenon.
Potential for Recurrence
Fleisher acknowledged the potential for similar situations to arise, given that the FDA often approves drugs for broader indications than studied populations and that trials frequently fall short of reflecting the U.S. population's ethnic and racial diversity. Controversy over surrogate endpoints for accelerated approval is also common.
The Role of Surrogate Endpoints
Fleisher expressed optimism that the FDA's efforts to foster scientific consensus on surrogate endpoints will lead to greater alignment between accelerated approvals and CMS coverage decisions.
Cost Considerations
Another distinguishing factor for Alzheimer's mAbs is their potential cost to the U.S. healthcare system. Biogen initially projected Aduhelm, priced at $56,000 per year, could consume a quarter of the Medicare Part B budget. While cost didn't dictate CMS's coverage decision, the potential burden on Medicare influenced the decision to develop a national coverage policy. Fleisher stated that while price doesn't influence coverage decisions, the population burden and total cost impact whether a national coverage analysis is initiated and a decision is made.