USA – The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for donanemab, Eli Lilly and Company’s investigational antibody therapy for Alzheimer’s disease (AD).

The Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over already available therapies that have received full FDA approval.

The FDA Breakthrough Therapy designation is based on clinical evidence for donanemab, an investigational antibody that targets a modified form of beta amyloid called N3pG.

The company’s Phase 2 trial, TRAILBLAZER-ALZ, studied the efficacy and safety of donanemab in patients with early, symptomatic AD.

The safety, tolerability and efficacy of donanemab are also being evaluated in the ongoing randomized, placebo-controlled, double-blind, multi-center Phase 3 study TRAILBLAZER-ALZ 2 (NCT04437511).

Eli Lilly plans to file for accelerated approval of its Alzheimer’s disease prospect donanemab later this year.

The planned filing on the strength of phase 2 data comes hot on the heels of the FDA’s decision to grant accelerated approval to Biogen’s Aduhelm.

Lilly is running a phase 3 clinical trial of donanemab but, with the FDA opening the door to approval of Alzheimer’s treatments without the normally required evidence of clinical efficacy, no longer sees a need to wait for the data before trying to get the product to market.

Lilly disclosed news of its plan as part of a statement about the FDA awarding breakthrough-therapy status to donanemab.

The anticipated filing seemingly poses another challenge to the FDA, as it may have offered encouragement to the company following granting them the Breakthrough Therapy designation.

The challenge stems from differences between the amount of data on donanemab and Aduhelm.

While Biogen failed to meet the bar for traditional approval, it tried to generate the required data and in doing so built a safety database featuring more than 3,000 subjects. Lilly has data on less than 500 subjects.

The data that are available are mixed from an efficacy perspective, with the drug failing to improve on placebo against the Clinical Dementia Rating Scale Sum of Boxes endpoint, but the precedent set by Aduhelm suggests evidence of a reduction in amyloid beta plaques on PET imaging will be enough for accelerated approval.