Lilly's Alzheimer's drug faces delayed reckoning
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The outlook for the latest experimental drug shown to delay Alzheimer's disease will come into focus Monday, when Food and Drug Administration advisers review an application from Eli Lilly that's been held up by questions about the design of clinical trials and safety risks.
Why it matters: Their conclusions could influence how the FDA treats future drugs that target proteins in the brain known as amyloid plaques that are believed to contribute to the development of the dreaded neurological condition that afflicts nearly 7 million people in the U.S.
State of play: Lilly's antibody donanemab was shown to be effective in slowing Alzheimer's progression by about a third, and it could become the second drug of its kind to receive FDA approval and corresponding Medicare coverage.
- It would compete with Eisai and Biogen's Leqembi, which the FDA approved last year but has been slow to take off amid questions about how to deploy it and whether insurers will cover the cost.
Friction point: Lilly had expected FDA approval to come early this year, but the agency in March unexpectedly called for an outside review of donanemab after some patients enrolled in a clinical trial experienced brain swelling, bleeding and other adverse events.
- An FDA staff briefing document prepared for today's advisory committee meeting cites disagreements between the agency and Lilly over the company's decision to change the measures of cognitive function used as the primary endpoint of the clinical trial.
- It also highlights how Lilly used PET scans to assess the amounts of another protein called tau that builds up in the brains of Alzheimer's patients, then used the results to select which participants would be monitored for disease progression over an 18-month period.
- It questions whether measured tau levels should be used to limit which patients get the drug, which would shrink the potential market for the treatment.
On safety, FDA staff noted there were 17 deaths in patients given donanemab, compared with 10 who received placebo. They said risks could be described in the prescribing information, including a boxed warning, similar to the one for Leqembi.
- Follow-up safety strategies could include MRI monitoring and expedited reporting of any patient deaths.
The other side: Lilly, in a rebuttal, said it wouldn't be necessary for prospective patients to get PET scans to measure tau levels, and that the company only did so in the trial to increase the likelihood it could "clearly determine" the drug's effect by enrolling patients whose condition was expected to get worse.
- It defended its use of endpoints, saying patients show clinically meaningful reduction of decline across different rating scales.
- And it stated "there is no evidence of an increase in risk of mortality or excess death related to donanemab," noting Alzheimer's irreversible, ultimately fatal nature and the way it can significantly increase the risk of acute conditions that can cause death.
Reality check: Even it wins approval, donanemab may have limited takeup because of safety concerns and because it's administered intravenously in hospitals and less convenient, Leerink analysts wrote in a research note on Sunday.
- They noted Biogen is expected to launch a more convenient, injectable version of Leqembi next year.
- Another Lilly experimental Alzheimer's treatment called remternetug that's now in clinical trials has shown promising results and could be more competitive, the analysts said.
