Lilly to seek FDA approval for Alzheimer’s drug that firm says slows decline
The trial results provided upbeat news for anti-amyloid treatments, a drug class that at times has been dogged by controversy and confusing data. But the study also showed why safety concerns continue to swirl around the drugs. Two participants in the trial died, with trial investigators attributing those deaths to complications from the drug. Those complications, called ARIA, typically involve brain swelling and bleeding. A third participant died after experiencing a serious incident of ARIA, but the investigator did not link the death to ARIA. Lilly said it could neither attribute the death to ARIA nor rule it out.
The donanemab trial, which included about 1,700 people with early symptoms of Alzheimer’s, is the latest evidence that the anti-amyloid drugs are “not without risk” and will require discussions between physicians and patients, said Ronald C. Petersen, an Alzheimer’s researcher at the Mayo Clinic in Rochester, Minn.
Nevertheless, he said, donanemab’s ability to slow cognitive and functional decline shows that “we are on the right track” in pursuing anti-amyloid therapies. Results from the Lilly trial and other studies involving two similar Alzheimer’s drugs suggest that lowering amyloid levels in the brain can produce “a clinical slowing of the disease, not huge, but a modest effect,” Petersen said. “If we can preserve the function in these individuals, we should consider it.”
Donanemab is administered intravenously once a month.
Indianapolis-based Lilly, which released its results in a news release Wednesday, said donanemab slowed the decline of participants by 35 percent over 18 months, measured by a tool that assesses cognition as well as activities such as managing finances, driving, engaging in hobbies and talking about current events. The company said it anticipated filing for FDA approval by the end of June.
The data has not been peer-reviewed. Lilly said it plans to submit the information to a peer-reviewed journal.
The 35 percent slowdown occurred in a group with a moderate level of a protein called tau, also linked to Alzheimer’s, in their brains. Researchers hypothesized that this group would be most likely to benefit from the drug because their illness had not advanced too far. When all participants were considered, including those with higher levels of tau, the drug slowed decline by 22 percent.
Within the group that showed a 35 percent slowing of deterioration over 18 months, 47 percent of participants showed no decline after one year compared with 29 percent in the placebo group.
In addition, because scans showed that amyloid plaques were effectively removed from their brains, 52 percent of participants were able to stop treatment after a year and almost three-quarters stopped after 18 months.
Some doctors were not enthused.
“Safety is the real issue with this class of drugs,” Robert Howard, a psychiatrist at University College London, said on Twitter. “Few are talking about it at the moment, but once we start to see significant numbers of patient deaths in clinic, it will be all over.” Other experts wondered if the slowdown in decline would be large enough for patients and their families to notice.
In January, the FDA rejected Lilly’s bid for accelerated approval for donanemab, saying it wanted safety data on more patients.
If federal regulators approve donanemab, there could be two anti-amyloid drugs on the market by late this year or early next year. In January, the FDA granted accelerated approval to a similar drug by Eisai and Biogen called Leqembi. Those companies have applied for full approval in hopes of gaining coverage by Medicare and other insurers.
Another Biogen drug, called Aduhelm, received accelerated approval from the FDA in June 2021. But confusing trial results soured physicians on the drug, Medicare never covered it, and it failed in the marketplace.