How donanemab data address the coverage with evidence development questions

Abstract The Centers for Medicare & Medicaid Services (CMS) established a class‐based National Coverage Determination (NCD) for monoclonal antibodies directed against amyloid for Alzheimer's disease (AD) with patient access through Coverage with Evidence Development (CED) based on three questions. This review, focused on donanemab, answers each of these CED questions with quality evidence. TRAILBLAZER‐ALZ registration trials are presented with supporting literature and real‐world data to answer CED questions for donanemab. TRAILBLAZER‐ALZ registration trials demonstrated that donanemab significantly slowed cognitive and functional decline in amyloid‐positive early symptomatic AD participants, and lowered their risk of disease progression while key safety risks occurred primarily within the first 6 months and then declined. Donanemab meaningfully improved health outcomes with a manageable safety profile in an early symptomatic AD population, representative of Medicare populations across diverse practice settings. The donanemab data provide the necessary level of evidence for CMS to open a reconsideration of their NCD. Highlights Donanemab meaningfully improved outcomes in trial participants with early symptomatic Alzheimer's disease. Comorbidities in trial participants were consistent with the Medicare population. Co‐medications in trial participants were consistent with the Medicare population. Risks associated with treatment tended to occur in the first 6 months. Risks of amyloid‐related imaging abnormalities were managed with careful observation and magnetic resonance imaging monitoring.