The U.S. Food and Drug Administration (FDA) has issued a draft guidance for the industry, proposing the use of Minimal Residual Disease (MRD) and Complete Response (CR) as primary endpoints to support accelerated approval for multiple myeloma treatments.
A Shift in Approval Endpoints Traditionally, drug developers relied on long-term indicators such as Progression-Free Survival (PFS) and Overall Survival (OS). However, as modern therapies have significantly extended patient lifespans (often 7 to 10 years for newly diagnosed cases), proving clinical benefits through these metrics has become increasingly time-consuming.
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MRD Defined: The FDA sets the threshold for MRD negativity at the detection of less than one tumor cell per 100,000 normal cells () in the bone marrow.
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CR as a Surrogate: Alongside MRD, achieving a Complete Response is recognized as a viable endpoint to speed up the delivery of novel agents to patients, particularly in earlier lines of therapy.
Context and Policy Debates The guidance follows a unanimous recommendation by the Oncologic Drugs Advisory Committee (ODAC) in 2024, despite internal debates within the agency:
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Counterarguments: Dr. Vinay Prasad (now Director of the FDA’s CBER) previously expressed concerns that MRD may not perfectly correlate with gold-standard survival rates and could overlook late-emerging safety signals.
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Technical Considerations: Experts point out that for innovative treatments like CAR-T therapies, patients may achieve MRD negativity in the bone marrow much faster than they reach a clinical Complete Response.
Market Implications While the recommendations are non-binding, they provide a roadmap for companies like Bristol Myers Squibb, Arcellx, and Regeneron to potentially trim years off their clinical trial timelines. The FDA encourages sponsors to utilize randomized trials to demonstrate that early MRD success translates into meaningful, long-term survival benefits for patients.