Eli Lilly is preparing to apply for FDA review of its experimental Alzheimer’s drug the same expedited route the agency used to approve Aduhelm from Biogen, and the company will do so with even less patient data than Biogen does Needed help with his medication.
The Indianapolis-based pharmaceutical giant said Thursday that an application for approval for the drug donanemab would be submitted later this year. This submission is based on the results of a single Phase 2 clinical trial that met its primary objective. The FDA had previously asked companies to submit data from two pivotal studies for an application for approval of an Alzheimer’s drug.
Expedited approval is a verification pathway that can get drugs to market faster based on less evidence than normally required. Approvals can be based on a surrogate endpoint, a sign in clinical trials that the drug may work even if the benefit to the patient has not been confirmed. For Biogen’s rapid approval of Aduhelm, this surrogate endpoint was clearing of the amyloid protein plaques in the brains of Alzheimer’s patients. The FDA based its Aduhelm decision on three studies with a total of 3,482 patients. In these studies, patients treated with the Biogen drug showed reductions in amyloid plaques, while patients given a placebo did not.
Like Aduhelm, Donanemab is a monoclonal antibody that targets amyloid. The Lilly drug is said to bind to a specific, modified form of the protein called N3pG and cause amyloid plaques to be cleared quickly and completely.
Lilly tested his Alzheimer’s drug in a phase 2 study that enrolled 272 patients who were randomly assigned to experimental therapy or a placebo. Those patients who were in the early stages of their disease were selected based on cognitive assessments and brain imaging that confirmed the accumulation of amyloid and tau protein in the brain characteristic of Alzheimer’s disease. The main aim of the study was to show changes over 76 weeks according to a composite rating scale that measures cognition and function.
According to test results published last month in the New England Journal of Medicine, the baseline for both groups was 106. At 76 weeks, the change in score for the donanemab group was -6.86. In the placebo group, the change was -10.06. This difference was enough to be statistically significant. Regarding the amyloid measurement, Lilly reported that the mean reduction was 84 centiloids compared to 108 centiloids at baseline. A negative amyloid scan is less than 25 centiloids typical, according to the company. However, little difference was seen between the Donanemab and placebo groups for several secondary goals that included other memory and function measurements.
“In early-stage Alzheimer’s disease patients, donanemab produced a better composite score for cognition and ability to perform daily activities than a placebo at 76 weeks, although the secondary results were mixed,” the paper’s authors write. “Longer and larger studies are needed to investigate the efficacy and safety of donanemab in Alzheimer’s disease.”
A longer and larger study is already underway. Lilly said a phase 3 double-blind, placebo-controlled study will continue. Around 1,500 patients are expected to take part in this study. Drugs submitted for review under the accelerated pathway can do so with phase 2 data. For approval, a company must conduct a large post-marketing study to confirm patient benefit. If the FDA approves donanemab, the ongoing Phase 3 test could become the confirmatory study for the drug.
Lilly revealed her plan to apply for FDA approval of donanemab in her announcement that the agency had named the drug “Breakthrough Therapy”. This designation expedites drug development and regulatory review for serious illness when early clinical data suggests the drug could improve therapies already available with full FDA approval.
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