The Food and Drug Administration's (FDA) Peripheral and Central Nervous System Drugs Advisory Committee has unanimously recommended the approval of the Alzheimer's drug donanemab. The 11-0 vote on Monday highlighted the drug's effectiveness in slowing the progression of Alzheimer's in its early stages, with the committee asserting that the benefits outweigh the risks associated with the medication.
Dean Follmann, a statistician at the National Institutes of Health and a member of the committee, remarked on the robust evidence supporting donanemab's efficacy. "The evidence that donanemab works is very strong," Follmann said. He acknowledged that while the drug does not cure Alzheimer's, it offers a meaningful delay in disease progression, which is significant for patients.
The FDA typically follows the recommendations of its advisory committees, suggesting that donanemab, developed by Eli Lilly, could soon join Leqembi, another Alzheimer's drug approved in 2023. Donanemab targets amyloid plaques, which are protein clumps that accumulate in the brains of Alzheimer's patients and are believed to contribute to the disease's progression.
One notable advantage of donanemab over Leqembi is its administration schedule. Donanemab is given monthly and can be discontinued if tests show a significant reduction in amyloid plaques, potentially allowing patients to stop treatment within a year. In contrast, Leqembi requires bi-weekly infusions indefinitely.
During the day-long discussion, the committee also addressed safety concerns. Both donanemab and Leqembi have been linked to brain swelling and bleeding, although these side effects are typically asymptomatic. However, they can be severe and have been associated with several deaths. The risks are particularly pronounced for individuals carrying two copies of the APOE4 gene, which increases the likelihood of developing Alzheimer's and experiencing adverse effects from the drug.
Despite these concerns, the panel emphasized the importance of providing access to the drug for all patients, including those at higher risk. Colette Johnston, the patient representative on the committee, advocated for broad availability, stating, "Yes, there is risk. But when you get a diagnosis of Alzheimer's, you don't have anything but risk."
The committee recommended that if donanemab is approved, doctors and patients should receive educational materials detailing the drug's risks. They also underscored the need for further research into the long-term effects of discontinuing treatment, such as the potential reappearance of amyloid plaques and whether patients should resume donanemab if that occurs.
Eli Lilly's journey to this point has been lengthy and fraught with challenges. The company initially applied for accelerated approval in January 2023, but the FDA requested additional safety data. Eli Lilly then sought traditional approval in mid-2023, with the FDA convening its advisory committee before making a final decision.
Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women's Hospital, spoke in favor of the drug's approval during the committee meeting. "It is critical to do whatever we can to have an impact to slow this terrible, inexorably progressive disease," Sperling said.
The committee also heard from patients who have participated in clinical trials. Myra Garcia, a 65-year-old Alzheimer's patient from Upland, California, shared her positive experience with donanemab. "Donanemab has been very, very helpful to me. I have been on the clinical trial for about two to three years, and I can tell you that I have had not a single bit of problem with it," Garcia testified.
