FDA delays Alzheimer’s drug for more review
The US Food and Drug Administration delayed regulatory action on an experimental Alzheimer’s drug that was widely expected to be approved this month, drugmaker Eli Lilly said Friday, citing a need for more review to establish its safety and effectiveness.
The FDA plans to hold an advisory committee meeting to further scrutinize Eli Lilly’s donanemab, one of few treatments developed for Alzheimer’s disease, a debilitating and incurable affliction that affects some 6 million Americans.
The agency’s action reflects a cautious approach, experts said, after approving a different Alzheimer’s drug in 2021 that showed conflicting data about its effectiveness — even as public pressure mounts for therapies to treat the memoryrobbing disease.
The call for additional scrutiny surprised Lilly executives, who said it is unusual for such a review to occur after the FDA has given an anticipated date to make a decision on approval.
“We are confident in donanemab’s potential to offer very meaningful benefits to people with early symptomatic Alzheimer’s disease,” Anne White, an executive vice president at Lilly, said in a statement. The company noted that the FDA held similar reviews for the two other amyloid-targeting drugs it previously approved.
The two approved drugs, known by their brand names as Aduhelm and Leqembi, drew heightened attention because of complications such as bleeding in the brain, with particular risk for patients that have a certain genetic variation and those taking blood thinners. Cambridge-based Biogen, which developed the two drugs with Japan’s Eisai, said in January it would cease marketing Aduhelm, a controversial drug that sputtered commercially after Medicare declined to broadly reimburse for it.
“The FDA was burned pretty badly with Aduhelm,” said Brian Balin, a professor at the Philadelphia College of Osteopathic Medicine who studies Alzheimer’s disease. Donanemab’s side effects could put patients with mild cognitive impairment at risk, he said, adding of the FDA’s action Friday, “I think it’s a wise decision.”
Jason Karlawish, associate director of the Alzheimer’s Disease Research Center at the University of Pennsylvania’s Perelman School of Medicine, said Eli Lilly’s clinical trials were well-designed. “This is not Aduhelm part two,” Karlawish said. “It’s fair to say that this decision is a surprise, but it’s not a cause for worry. The data shows [donanemab] is effective.”
The FDA doesn’t comment on drugs that are pending approval.
Donanemab is designed to attack a sticky substance in the brain known as amyloid beta, which has been linked to Alzheimer’s. Clinical trials have shown that donanemab slows cognitive decline of people in the early stages of the disease, but the promise of amyloid-targeting drugs remains divisive within the field.
Those drugs don’t reverse the effects of the disease, said Marwan Sabbagh, a behavioral neurologist at the Barrow Neurological Institute who served on the advisory committee for Leqembi.
“The reality is these patients are less worse,” Sabbagh said of amyloid-targeting drugs. “They do not actually get better on these drugs, but we slow the rate of decline.”
Matthew Schrag, a neurologist at Vanderbilt University Medical Center, continues to be skeptical of the focus on amyloid to treat Alzheimer’s. “The absolute magnitude of the benefit is very small,” he said. “I think it is entirely appropriate that the FDA thoroughly vets donanemab and avoids the perception that the approval process is rushed.”
Donanemab, which is administered once a month by infusion, showed in clinical trials that it slowed the mental decline of participants by 35 percent, as measured by cognitive tests and activities like driving and managing finances. But it also aroused safety concerns, with trial investigators attributing the deaths of two participants to a complication from the drug. That complication, known as ARIA, usually involves swelling or bleeding in the brain, and has dogged Aduhelm and Leqembi as well.