In a recent development, the Food and Drug Administration (FDA) has decided to delay the approval decision for Eli Lilly's experimental medicine aimed at treating Alzheimer's disease. This decision comes as the FDA plans to convene an advisory committee meeting to conduct a more thorough evaluation of the drug's safety and effectiveness.

Eli Lilly disclosed that the FDA is seeking additional insights into the "unique" design of the pivotal study supporting the company's approval application. Notably, this study permitted participants to discontinue the drug, donanemab, once it successfully cleared amyloid protein clumps from their brains. The FDA is particularly interested in understanding the safety profile of donanemab, given its association with a type of brain swelling, a characteristic shared with other Alzheimer's drugs.

The expected verdict on donanemab, initially anticipated by the end of March, will now be postponed due to the advisory committee meeting, extending the decision date beyond the first quarter.

In a recent media release, Wli Lilly revealed that the FDA will convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) to discuss the Phase 3 TRAILBLAZER-ALZ 2 trial. This trial focused on evaluating the efficacy and safety of donanemab in individuals with early-symptomatic Alzheimer's disease.

The FDA has communicated to Lilly its desire to delve deeper into various aspects of assessing the safety and efficacy of donanemab. This includes scrutinising safety results in patients treated with donanemab and understanding the implications of the unique trial design of the TRAILBLAZER-ALZ 2 study. The latter featured a limited-duration dosing regimen, allowing patients to conclude treatment based on an assessment of amyloid plaque and the inclusion of participants based on tau levels.

The exact date for the advisory committee meeting is yet to be determined by the FDA, resulting in the delay of the expected FDA action on donanemab beyond the initial quarter of 2024. While the occurrence of an advisory committee meeting after the anticipated FDA action date is uncommon, it follows a similar pattern to meetings held for two other FDA-approved amyloid plaque-targeting therapies.

Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience, expressed confidence in donanemab's potential to provide meaningful benefits to those with early-symptomatic Alzheimer's disease. She acknowledged the unexpected nature of the advisory committee meeting but affirmed the company's readiness to present the TRAILBLAZER-ALZ 2 results and contextualise donanemab's efficacy in terms of safety.

TRAILBLAZER-ALZ 2, a Phase 3 double-blind, placebo-controlled study, evaluated the safety and efficacy of donanemab in participants aged 60–85 years with early symptomatic Alzheimer's disease. The trial, involving 1,736 participants across eight countries, selected individuals based on cognitive assessments, amyloid plaque imaging, and tau staging by PET imaging.

Compared to participants in similar trials of other amyloid plaque-targeting therapies, TRAILBLAZER-ALZ 2 participants were more advanced in their disease progression. Regardless of tau level, all groups of trial participants benefited from treatment with donanemab, with those in earlier disease stages experiencing the most significant results. The drug also demonstrated clinical benefits with a limited-duration treatment regimen, with nearly half of the participants completing their course of treatment in six or 12 months.

A key risk associated with donanemab is amyloid-related imaging abnormalities (ARIA), which can be serious and life-threatening. Other commonly reported risks include infusion-related reactions, headaches, and nausea.

Results of the trial published in JAMA in July 2023, researchers concluded that donanemab significantly slowed clinical progression at 76 weeks among participants with early symptomatic Alzheimer's disease and amyloid and tau pathology, especially in those with low or medium tau and in the combined low, medium, and high tau pathology population.