So far, the FDA has granted accelerated approval to two Alzheimer’s drugs. Eli Lilly’s amyloid plaque removal therapy won’t become the third. The Lilly drug still has a chance to pass regulatory testing, but that will take more data and more time.
Lilly announced the full response to the letter Thursday night. According to Lilly, the FDA cited a lack of data from patients who had been treated with the drug donanemab for at least 12 months. The agency wants to see such data from at least 100 patients.
“Although the trial included more than 100 patients treated with donanemab, due to the rate of plaque reduction, many patients were able to discontinue dosing as early as six months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab,” Lily I said. “FDA has indicated that data to meet exposure expectations will likely need to include unblinded controlled safety data from TRAILBLAZER-ALZ 2 upon completion.”
TRAILBLAZER-ALZ 2 is the ongoing confirmatory phase 3 trial. Preliminary data from this study is expected in the second quarter of this year. Lilly said that when those results are available, they will form the basis of an application seeking traditional regulatory approval.
The The 2021 approval of Biogen’s Aduhelm made it the first Alzheimer’s drug to reach the market under accelerated FDA approval. Two weeks ago, Eisai’s Leqembi received fast-track FDA approval along the same route. Both drugs target and break down amyloid, the protein that forms plaques on the brains of Alzheimer’s patients.
Like the Biogen and Eisai drugs, donanemab is also an antibody that targets amyloid. But the Lilly drug is designed to target a modified form of beta amyloid plaque called N3pG. The Phase 2 trial of donanemab included 272 Alzheimer’s patients in the early stages of the disease; 131 in the study drug group and 126 in the placebo group. The primary objective was to measure at week 76 the change in outcome on a composite rating scale measuring cognition and function.
The results of the Phase 2 study were published in 2021 in the New England Journal of Medicine. Comparison of the donanemab group with the placebo group showed a statistical difference in the change in outcomes. But the study’s primary endpoint assessment at week 52 had only 88 patients in the donanemab arm. Study discontinuations were more common in the donanemab arm. In that group, seven participants dropped out of the clinical trial — two of them because of brain hemorrhage, a side effect that is a known complication of Alzheimer’s drugs that target amyloid. Lilly said the safety profile of donanemab has been consistent since the company submitted its application for accelerated approval.
Besides the lack of data on at least 100 patients after a year of treatment, Lilly said the FDA cited no other problems with its application.
“We look forward to our upcoming confirmatory Phase 3 results of TRAILBLAZER-ALZ 2 and the subsequent FDA submission, which we have always seen as the most impactful next steps for patients,” said Anne White, executive vice president of Lilly Neuroscience, in a prepared statement. “We expect this study to confirm the benefit and safety profile we observed in the Phase 2 trial of TRAILBLAZER-ALZ, and we believe patients and physicians will be well served by having the complete Phase 3 data alongside our Phase 3 data 2 when they have to make treatment decisions.”
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