Drugmaker Eli Lilly says that approval of its experimental Alzheimer’s medication donanemab will be delayed beyond the end of March as the US Food and Drug Administration plans to call a last-minute meeting of its outside advisers to review the drug’s safety and efficacy.
The medicine had been expected to be cleared by the end of the first quarter of this year, after being pushed back already from an expected approval last year. It would follow Eisai and Biogen’s Leqembi to market as the second drug shown to slow the course of the memory-robbing disease, which affects more than 6 million Americans. Both drugs work by targeting plaque buildups in the brain that are known as amyloid.
The FDA told Lilly that it plans to call the advisory meeting to discuss the safety of donanemab, as well as the design of a key clinical trial supporting its application, called Trailblazer-Alz 2, the company said in a news release Friday. The date for the meeting hasn’t been set, Lilly said.
“We are confident in donanemab’s potential to offer very meaningful benefits to people with early symptomatic Alzheimer’s disease,” Lilly Neuroscience President Anne White said in the 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.”
The main safety concerns with these medicines are brain swelling and micro-hemorrhages known as amyloid-related imaging abnormalities, or ARIA. In donanemab’s Phase 3 clinical trial, 37% of participants had ARIA, including three who died.
Leqembi has been tied to patient deaths as well, although its rate of ARIA was lower in trials.
Lilly said the FDA also wanted its outside experts to weigh in on the “unique trial design” of the donanemab study, which allowed patients to stop taking the drug once the amyloid plaques were shown to be cleared from the brain. Other Alzheimer’s drugs, including Leqembi, don’t have designated stopping points.
The trial was also different in that it separated patients into groups based on their levels of another Alzheimer’s-related protein called tau. It found that among participants characterized as having “intermediate” levels of tau, those taking donanemab had a 35% slower decline in the ability to think clearly and perform daily tasks compared with those taking a placebo.
When people with high levels of tau — who are thought to be further along in the disease — were included, the benefit compared with placebo was 22%.
Leqembi received full approval from the FDA in July, a decision that triggered broader Medicare coverage. But the drug has been off to a slow start, with only about 2,000 people taking it, Biogen said on its quarterly earnings call February 13. That may reflect some of the challenges of these medicines, which require a number of scans and tests before starting and throughout treatment.
The FDA’s had a tortured history with recent Alzheimer’s drug approvals. It cleared a predecessor drug to Leqembi, called Aduhelm, in 2021 against the recommendation of its advisory panel, and the Centers for Medicare and Medicaid Services limited coverage for the drug, citing a lack of evidence behind it. The medicine never took off, and Biogen discontinued it in January.