Lilly's Alzheimer's med donanemab delayed as FDA seeks late advisory committee meeting

Eli Lilly’s donanemab has been delayed at the FDA for approval in Alzheimer’s disease, a blow to the company’s efforts to get what could be a $2.8 billion per year opportunity by 2028.

The FDA now plans to convene an advisory committee meeting to discuss the phase 3 TRAILBLAZER-ALZ 2 trial that underpinned the application for the monoclonal antibody. The agency specifically wants to further discuss issues related to the safety and efficacy of the med, including safety results in patients who received donanemab and the efficacy implications of the trial’s unique design, Lilly said in a Friday morning release.

“It was unexpected to learn the FDA will convene an advisory committee at this stage in the review process, but we look forward to the opportunity to further present the TRAILBLAZER-ALZ 2 results and put donanemab's strong efficacy in the context of safety," said Anne White, executive vice president of Eli Lilly and Co., and president of Lilly Neuroscience. “We will work with the FDA and the stakeholders in the community to make that presentation and answer all questions.”

For the trial design, the FDA has questions about the limited-duration dosing regimen that lets patients stop treatment once they reach a certain lowering of amyloid plaque, as well as inclusion of participants based on tau levels.

The dosing regimen has dogged Lilly before, as the FDA denied an accelerated review in January 2023 because of the limited number of patients who had been on the drug for 12 months or more. In explaining the dosing regimen after the accelerated review issues, Lilly said that patients experienced swift reduction of their plaques, which allowed them to stop treatment as early as six months in.

A date for the meeting has yet to be set, but it represents a huge delay for Lilly, which had expected approval of the med by the end of this quarter. The matter will be handled by the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee. Lilly did not revise an expected launch date for the drug, beyond saying that the adcomm would delay things beyond the first quarter.

“While it is unusual for an advisory committee to occur after the anticipated FDA action date, the advisory committee meeting for donanemab follows similar meetings for the two other amyloid plaque-targeting therapies the FDA has approved,” Lilly said in the release.

Executives had reiterated the end-of-Q1 expectation in an early February earnings call, speaking at the TD Cowen 44th Annual Health Care Conference on Wednesday, Lilly’s Andrew Adams, vice president of new therapeutic modalities and scientific leader, was a bit more reserved, telling an analyst that it was “a big file.”

“It wasn't intended to not be reassuring. It's a completely normal experience thus far. I've been part of that from assessing questions and feedback and things that we've provided,” Adams said. “There is nothing that I've experienced on that filing that's out of the ordinary for a trial of that magnitude and an indication as important as Alzheimer's disease. So I would suggest that we just have to follow the timeline set by the agency. And it's really out of our control, their review process, once we provide the data that they've asked for.”

The TRAILBLAZER-ALZ 2 trial set a new marker in Alzheimer’s disease when donanemab showed a 35% slowing of cognitive decline and a 39% lower risk of advancing to the next stage of the disease when compared to placebo. The results seemed to best Biogen and Eisai’s Leqembi, which is already on the market under an accelerated approval.