Lilly’s Donanemab Granted FDA Breakthrough Therapy Status

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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donanemab, breakthrough therapy designation


The U.S. Food and Drug Administration has named Eli Lilly’s donanemab a breakthrough therapy for treating Alzheimer’s disease, the company announced in a press release.

Lilly said it intends to submit a biologics license application or BLA — which would allow it to market donanemab in the U.S. — to the FDA later this year.

The breakthrough therapy designation is intended to speed the development and review of treatments for serious medical conditions. To receive such status, candidate therapies must demonstrate significant improvement over already existing FDA-approved treatments.

The FDA’s decision was based on results from the TRAILBLAZER-ALZ study, a Phase 2 trial (NCT03367403) sponsored by Lily that evaluated donanemab’s safety, tolerability, and efficacy in adults with early stage, symptomatic Alzheimer’s.

The study results were presented at the recent 15th International Conference on Alzheimer’s & Parkinson Diseases, and subsequently published in the New England Journal of Medicine, in an article titled “Donanemab in Early Alzheimer’s Disease.”

Donanemab is an antibody designed to recognize a harmful form of the beta-amyloid protein that clumps into toxic plaques in Alzheimer’s patients. Antibodies trigger immune reactions by attaching themselves to their target molecules — in this case, toxic amyloid clumps — labeling them as harmful.

In this way, donanemab can recruit cells from the immune system to clear such amyloid plaques, which is expected to slow Alzheimer’s progression.

TRAILBLAZER-ALZ enrolled 257 patients, ages 60–85, who were randomly assigned to receive either donanemab, or a placebo, both given intravenously (into the vein).

The main goal of the study was to evaluate changes in the integrated Alzheimer’s Disease Rating Scale or iADRS, a measure of cognition and daily life abilities. Participants were evaluated, using iADRS, from the beginning of the study until 76 weeks (almost 1.5 years) of treatment.

Secondary goals included evaluating changes in other measures of cognition, memory, and activities of daily functioning. Brain amyloid and tau deposits also were measured.

The results showed donanemab was able to slow cognitive decline and the loss of daily life abilities when compared with a placebo. Outcomes in the secondary trial goals were more mixed, however, and not all time points measured showed statistical significance.

Importantly, donanemab cleared amyloid plaques more effectively than did the placebo.

Lilly now plans to submit a BLA for donanemab to the U.S. regulatory agency for approval, based on data from TRAILBLAZER-ALZ. The BLA is a request for permission to introduce a biologic product into interstate commerce. According to Lily, that request will be made later this year, through the FDA’s accelerated approval pathway.

In addition to TRAILBLAZER-ALZ, two other clinical trials are currently assessing the safety and efficacy of donanemab for patients with early Alzheimer’s. These include the study’s long-term extension, TRAILBLAZER-EXT (NCT04640077), and a Phase 3 trial, called TRAILBLAZER-ALZ 2 (NCT04437511).

TRAILBLAZER-ALZ 2 is currently recruiting participants at 326 sites worldwide. Eligible patients will be ages 60-85 with gradual and progressive change in memory function for at least six months. More information on contacts and locations can be found here.