The FDA has delayed its decision on Eli Lilly’s highly anticipated Alzheimer’s drug donanemab and plans to convene an advisory committee to review it in a surprise delay for a treatment that many experts had expected would be approved with relative ease.
The agency has additional questions about donanemab’s safety, the clinical trial design, the decision to take patients off the drug once it clears amyloid plaques from the brain, and Lilly’s stratification of patients based on how much tau protein is in their brain – where higher levels indicate a more advanced disease.
Endpoints News reports that this is the second delay for the drug, which Lilly had originally expected would get an approval decision in late 2023.
In November, Lilly announced that regulators had asked for extra time to review the data, pushing back an approval decision to the first quarter of this year.
It’s unclear how long this new delay will last – a date for the adcomm meeting has not been set.
Advisory committee meetings are not unusual, especially when there are questions about a treatment’s relative benefits and risks, but usually, they are scheduled earlier in a drug’s review process.
An adcomm for donanemab seemed unlikely since two meetings were already held for similar amyloid-busting antibodies, including Eisai and Biogen’s Leqembi, which won full FDA approval last summer.
While Leqembi was hailed as the first new drug to win a full-throated FDA approval in two decades, sales of the treatment have been off to a slow start. Donanemab’s delay could give Biogen and Eisai some extra breathing room.
A Lilly spokesperson said many of the FDA’s questions centred around safety. The spokesperson noted that there were potentially important differences in the kinds of patients who got donanemab, compared with those who got Leqembi.
Even though patients in both trials were in the early stages of cognitive impairment or dementia, patients in the Lilly trial had higher amounts of amyloid plaques in the brain, the spokesperson said, suggesting a slightly more advanced condition.
Donanemab was about twice as likely as Leqembi to cause signs of brain swelling and bleeding, which were attributed to three deaths in the 1 800-person study.
Lilly also divided patients in its trial based on the amount of tau protein in their brains, and the efficacy of its drug varied greatly depending on whether they had high or low tau levels.
Those with higher tau, and thus more advanced disease, got considerably less benefit.
And while Leqembi is supposed to be administered every two weeks indefinitely, patients in Lilly’s trial stopped taking donanemab once brain scans revealed that most of their amyloid plaques had been cleared. While this could be one of the major perks of Lilly’s treatment, it’s unclear when or if patients would need to get the drug again.
It’s also possible that regulators could have questions about Lilly’s decision to use a novel measurement of cognitive decline in its study, which led to a widely cited figure suggesting donanemab was more effective than Leqembi. The difference between the drugs was much smaller on a more widely used scale.
Some Alzheimer’s advocates were quick to frame the delay as part of the FDA’s “due diligence” for a ground-breaking class of drugs.
“The FDA decision is not a setback, but another step forward in the drug approval process,” Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said in a statement. “The decision to hold an advisory committee before granting approval follows the regulatory process that was used for the other drugs in this class, including Leqembi.”
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