FDA Advisory Panel Unanimously Supports Eli Lilly’s Experimental Alzheimer’s Drug

Outside advisers to the U.S. Food and Drug Administration (FDA) have given a unanimous endorsement to Eli Lilly’s experimental Alzheimer’s treatment, donanemab, concluding that the drug's benefits outweigh its risks. The advisory panel agreed that trial data demonstrated effectiveness in patients with early-stage Alzheimer’s. This vote paves the way for a final FDA decision on the treatment, which had been anticipated earlier this year before the agency convened the meeting for its independent experts to deliberate.

Following the vote, Dawn Brooks, Lilly’s development leader for donanemab, expressed satisfaction with the committee's recognition of the drug’s positive benefit-risk profile. "We really are pleased that the advisory committee recognized donanemab’s strong positive benefit risk," she said. The company now looks forward to the FDA completing its review.

While the FDA is not obligated to follow the recommendations of its outside advisers, it typically does so. During the discussion, the FDA asked the panel to consider unique aspects of Lilly’s trial, which significantly differed from the trial design of Eisai and Biogen’s Leqembi, which received U.S. approval after a similar advisory committee meeting. Both drugs aim to remove toxic beta amyloid plaques from the brains of individuals with early Alzheimer’s.

These antibody treatments have successfully slowed disease progression in clinical trials, following three decades of failed attempts to develop drugs to combat this fatal cognitive disorder. A key distinction in Lilly’s trial design was the measurement of tau, a second Alzheimer’s-related protein associated with brain cell death, to select patients most likely to benefit within the study’s 76-week period.

Consequently, Lilly excluded patients with very low or no tau levels from the pivotal trial but conducted a separate analysis of this group in another large study to assess the drug’s effects. Several panelists indicated that this data suggested a potential treatment benefit. Panel members largely agreed that tau testing should not be mandatory before treatment, noting that its limited availability could restrict access for rural or underserved populations.

The panel also discussed elevated safety concerns for individuals carrying two copies of the APOE4 gene, which is linked to a higher risk of Alzheimer’s. They suggested that doctors should educate patients about these risks and consider them when prescribing the drug.

In Lilly’s large clinical trial, donanemab, administered via infusion once a month, slowed the progression of memory and thinking problems by 29%, roughly comparable to the 27% reduction seen with Leqembi. Brain swelling and bleeding, known risks for this class of drugs, occurred in 24% and 31% of those taking donanemab, respectively, with three patients dying as a result.

In Eisai and Biogen’s late-stage study, 12.6% of participants taking Leqembi experienced brain swelling, and 17.3% suffered brain bleeding. Leqembi was approved with the FDA’s strongest “boxed” warning about the risk of potentially dangerous brain swelling and bleeding, applicable to all drugs in this category.

Several panel members praised Lilly’s innovative trial design, which allowed participants to discontinue treatment once brain imaging showed the amyloid plaque had been cleared. However, they noted that this could complicate decisions for doctors regarding when to stop and restart treatment if necessary.

Lilly announced plans to conduct trials to test donanemab in patients genetically predisposed to develop Alzheimer’s, including individuals with Down syndrome.

Jefferies analyst Michael Yee commented in a note to clients that the vote “sets up an eventual FDA approval,” adding that having two competitors in the market would be beneficial in the long term. Shares of the Indianapolis-based drugmaker closed up 1.8% at $865.