- Eli Lilly plans to seek accelerated Food and Drug Administration approval for its experimental Alzheimer's medicine donanemab, announcing Thursday plans to file an application with the agency later this year.
- The decision is a reversal for Lilly. In April, a top company executive told investors that Lilly didn't think it could submit donanemab for an accelerated OK based on the clinical trial evidence it has accrued. But earlier this month the FDA controversially cleared Biogen's Alzheimer's drug Aduhelm on a conditional basis, citing the therapy's effect on brain plaques associated with the disease. Donanemab works similarly.
- Lilly also said the FDA had granted Breakthrough Therapy designation for donanemab, a step that opens up closer collaboration between the agency and the company as well as speeds the FDA's review. Shares in Lilly rose by nearly 8% in pre-market trading Thursday on the news.
The FDA's accelerated approval of Aduhelm appears to have set a precedent that Lilly is now following. In clearing Aduhelm, the agency based its decision on how well the drug removed the sticky clumps of amyloid, a key protein in Alzheimer's, from the brain. This reduction in amyloid, the FDA said, was "reasonably likely" to translate to slower cognitive decline in patients with the disease.
The approval is highly controversial, however, both because the link between amyloid clearance and clinical benefit remains fiercely debated, and because evidence from two large clinical trials of Aduhelm was contradictory. One study showed treatment with a high dose led to a roughly 20% slower decline in cognition and function than did placebo. The other did not, raising concerns among many experts that the seeming effectiveness in the first trial could be a "false positive" result.
FDA officials, excepting the team tasked with a statistical review of Biogen's results, were convinced, however, and have strongly defended their decision since the June 7 approval.
The news from Lilly on Thursday suggests the agency may be open to similar approvals as well, a possibility that had lifted the drugmaker's shares even before the company's announcement.
Results from a Phase 2 study, published in The New England Journal of Medicine, show Lilly's drug dramatically reduced amyloid plaque in the brains of trial participants. By 76 weeks, the end of the study, roughly 68% of the 131 patients who had received donanemab were considered negative for brain amyloid.
Researchers also observed slower cognitive and functional decline, as measured by a rating scale, among donanemab-treated patients. The results were encouraging, but some experts questioned the magnitude of benefit.
"[Donanemab] actually did move the needle a tiny bit in the context of dramatically clearing amyloid." said David Knopman, a neurologist and Alzheimer's specialist at the Mayo Clinic, in an April interview with BioPharma Dive. "But the effect size in the donanemab trial was very small. Is that the best we can do?"
The data published in NEJM also showed treatment with donanemab did not meet several secondary goals of the study, although the trial's small size made that harder to do.
With accelerated approval, however, Lilly does not need conclusive proof donanemab leads to significant clinical benefit, only that its effects are reasonably likely to predict an eventual improvement. The drug's clear impact on amyloid, following the FDA's acceptance of amyloid reduction as a surrogate marker for Aduhelm's efficacy, could be enough for the agency to agree to review the drug.
"We think it would make zero sense for FDA to approve Aduhelm, but not donanemab," wrote Brian Skorney, an analyst at Baird who has been critical of the data supporting Aduhelm, in a note to investors Thursday.
Lilly also has already started a Phase 3 study of donanemab that could yield results by mid-2023 and, if the drug were to be approved, potentially serve as a confirmatory study. Biogen has not yet begun a required confirmatory trial of Aduhelm.
Skorney argues Aduhelm's accelerated approval and Lilly's decision to ask for the same could "be the beginning of a broader trend" that might see other amyloid-targeting drugs submitted to the agency. Roche, for instance, is still developing a treatment that had previously failed in late-stage studies.
On Wednesday, meanwhile, Japanese drugmaker Eisai and Biogen announced the FDA had granted a Breakthrough Therapy designation for lecanemab, another amyloid antibody developed through their partnership. While they didn't say whether they would seek accelerated approval based on data they already have, results from a Phase 3 study of the drug are expected by next fall.
Note: This story has been updated to include mention of additional trials of donanemab and Aduhelm.