Despite concerns raised in FDA briefing documents about Eli Lilly’s Alzheimer’s treatment, donanemab, the committee concluded that the benefits outweighed the risks.
On Monday, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted unanimously, 11 to zero, in favor of Eli Lilly’s Alzheimer’s treatment, donanemab. The group of advisors not only determined donanemab to be an effective treatment for Alzheimer’s disease with mild cognitive impairment and mild dementia, but that the benefits outweigh the risks.
Kathleen Poston, the director of the neurological science at Stanford’s Movement Disorders Center, voted yes because she felt the clinical data across subgroups and the biomarker data were “convincing of the effect,” she said in the adcomm vote.
When Eisai and Biogen’s Leqembi was approved last year, it became the first real treatment option to target a suspected underlying cause of the disease: amyloid beta plaques. The FDA had previously granted accelerated approval to Biogen’s Aduhelm, but the approval triggered debate over the effectiveness of the drug, which was eventually discontinued. Meanwhile, Leqembi has started pulling in a profit for Eisai and Biogen after a slow start. The treatment generated $19 million in sales in the first quarter of 2024, a jump from $7 million in the last three months of 2023.
Donanemab, also an anti-amyloid therapy, would be a direct competitor of Leqembi. An analyst report from Jefferies noted that if donanemab is approved, having two players on the market could be beneficial for Lilly, Eisai and Biogen in the long term.
“We believe having two players on the market is a win-win for both [Eisai/Biogen] and [Eli Lilly] as there’d be more efforts and stronger advocacy on increased investments from centers in building out infrastructure and allocating more resources, and also driving more patient and physician education,” the Jefferies report said.
Not Without Concern
While the adcomm’s decision was favorable for Lilly, the FDA raised several questions about the efficacy and safety of the drug. One of the primary concerns in the agency’s briefing documents was Lilly’s use of its integrated Alzheimer’s Disease Rating Scale (iADRS). Lilly developed the scale, which, according to the National Institutes of Health, combines scores from two accepted measures for assessing Alzheimer’s. However, the FDA said the donanemab trial was initially designed with a different endpoint that changed during the study, and the agency said in 2021 that it did not agree that iADRS should be used.
The briefing document also criticized Lilly’s use of tau protein levels to decide who to include in the study. Patients with none to very low levels of tau were excluded, and the FDA asked the committee to assess the data and the “effectiveness across the subgroups based on tau PET imaging.”
The adcomm discussed tau but ultimately it did not have a major effect on the vote. Adcomm member Cynthia Carlsson, a senior professor at the Wisconsin Alzheimer’s Disease Research Center, said in her affirmative vote that she does not think the tau analysis is “necessary” as it “doesn’t have any clear impact on scientific validity” and added that using tau to determine which patients are eligible to receive donanemab treatment would be a barrier to access.
Several committee members did note a lack of data on underrepresented groups such as African Americans and Hispanics, as well as patients with Down syndrome and autosomal-dominant Alzheimer’s disease patients. Members of the committee said that more information was required to understand donanemab’s effect on these populations.
Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.
