Eli Lilly shut out of Alzheimer's fast lane with FDA rejection for donanemab

Eli Lilly’s bid for an accelerated approval of Alzheimer’s disease drug donanemab has been shut down by the FDA.

The Indianapolis pharma received a complete response letter from the agency, according to a late Thursday press release. Lilly had been seeking a nod to treat early cases of symptomatic Alzheimer's disease. The FDA rejected the request due to the limited number of patients who had seen at least 12 months of drug exposure in a clinical study, according to the company. The agency did not flag any other issues.

Lilly’s application was based on a phase 2 trial that showed a decrease in amyloid plaques within the brain, which has been used as a surrogate biomarker for efficacy against Alzheimer’s. Therapies can be approved under the FDA's accelerated pathway based on biomarker evidence, so long as the company conducts a confirmatory trial to demonstrate stronger efficacy in the future. 

Donanemab is currently in a phase 3 trial called TRAILBLAZER-ALZ 2 that Lilly hopes will do just that. A top-line readout is expected in the second quarter, and, without the accelerated nod, Lilly will have to wait for those data to put forward a full application. The company said a traditional approval filing will occur shortly after that data release.

That puts the company well behind Eisai and Biogen, which in December received an accelerated OK for lecanemab, now known as Leqembi. Lilly was already gearing up to launch donanemab with an expected FDA nod sometime this year.

The FDA requested data from a minimum of 100 patients after at least a year of continued treatment with donanemab. The original TRAILBLAZER-ALZ study that formed the accelerated review application treated patients until they reached a certain level of amyloid plaque clearance, at which point patients stopped treatment.

“While the trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as six months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab,” Lilly explained in the release.

The FDA also said the exposure information they are looking for will likely need to include unblinded, controlled safety data from the ongoing TRAILBLAZER-ALZ 2 study once it’s complete.

Lilly said the safety of donanemab has been reported and has remained consistent since the company submitted the accelerated approval application. 

The setback does not change Lilly’s 2023 financial guidance, according to the company's release.