FDA panel endorses Lilly's Alzheimer's drug

Eli Lilly's anti-beta amyloid antibody, donanemab, has taken a significant step towards FDA approval after an advisory committee unanimously endorsed its safety and efficacy for treating Alzheimer's disease. The committee's 11-0 vote reflects a favorable assessment of donanemab's risk-benefit profile, despite notable safety issues highlighted in pre-meeting documents.

Prior to the meeting, FDA staff raised concerns about a higher incidence of amyloid-related imaging abnormalities (ARIA) in patients treated with donanemab compared to those on a placebo. This included three ARIA-related fatalities. In comparison, the safety data for donanemab is less robust than that of Eisai and Biogen’s Leqembi (lecanemab). Nevertheless, the advisory committee emphasized the importance of educating both patients and healthcare providers to manage these risks effectively.

Kathleen Poston, director of neurological sciences at the Stanford Movement Disorders Center, pointed out that frequent MRI scans to monitor for ARIA pose a significant burden. Interpreting these scans is complex and could be challenging, especially in areas without access to specialized neuroradiologists. As such, Poston stressed the need for comprehensive education regarding the interpretation of MRI scans to ensure proper risk monitoring.

Committee member Colette Johnston, a patient advocate, highlighted the importance of individual choice in managing Alzheimer’s disease. She argued that the potential benefits of donanemab justify the risks, and that patients, along with their caregivers and healthcare providers, should make informed decisions. Johnston emphasized that, while donanemab is not perfect, its benefits are acceptable from her perspective as a caregiver.

The advisory committee did not question the efficacy of donanemab for patients with mild cognitive impairment and mild dementia, voting unanimously in favor of its use. However, several members called for additional data on underrepresented populations, particularly African Americans and Hispanics. Poston noted that this subgroup data would be crucial in ensuring that the positive findings from donanemab studies are applicable to all individuals with Alzheimer’s disease.

In the Phase III TRAILBLAZER-ALZ 2 study, which spanned 18 months, donanemab demonstrated a 29% reduction in cognitive and functional decline based on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), aligning closely with Leqembi's 27% reduction. However, eligibility for the donanemab trial required participants to test positive for tau on PET scans, with two groups analyzed based on tau levels: low/medium and the overall population.

Some analysts speculate that donanemab, if approved, might come with a more restrictive label than Leqembi, necessitating patients to undergo tau-detecting PET scans. However, the advisory committee largely opposed adding this requirement, citing access issues. Cynthia Carlsson, a professor of medicine and Alzheimer's disease at the University of Wisconsin, argued that requiring tau PET scans would be impractical for many communities. She emphasized that the existing data and scientific understanding of amyloid and tau progression do not justify this additional burden.

Summarizing the committee's position, chair Thomas Montine stated that the majority believe a tau imaging requirement is unnecessary and would pose significant practical and access challenges for patients seeking treatment.

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