Trial to Test Donanemab in People With Alzheimer’s Signs, Not Symptoms

A new Phase 3 trial, a collaboration between Eli Lilly and the Banner Alzheimer’s Institute, is planned to evaluate the potential of donanemab in preventing  the cognitive and functional decline related to Alzheimer’s disease.

Called TRAILBLAZER-ALZ 3, the study will enroll people with “evidence” of Alzheimer’s but no clinical symptoms. Those with and without the ApoE4 gene variant, a known genetic risk factor for Alzheimer’s disease, are eligible to participate.

The trial “will evaluate whether donanemab can prevent clinical progression in patients who have evidence of Alzheimer’s pathology, but don’t yet demonstrate clinical symptoms,” Mark Mintun, MD, vice president of pain and neurodegeneration at Eli Lilly, said in a press release. Lilly is developing donanemab.

Patient recruitment — expected to start by the end of the year — will be conducted through Banner’s Alzheimer’s Prevention Registry GeneMatch program.

“While these types of trials are challenging to enroll and conduct, Lilly, together with Banner, is proud to undertake the opportunity to bring about this new study in an area of high unmet medical need,” Mintun said.

By signing with the registry, which can be done here, patients will receive information about upcoming clinical studies and be able to participate in those they chose and qualify for, as well as research updates and news related to Alzheimer’s. Information provided to the registry is kept safe and private.

Low patient enrollment is a major roadblock in clinical research, with 80% of studies being delayed due to such difficulties. The registry was established as a way to bring together patients and scientists at the forefront of Alzheimer’s research, and boost patient enrollment.

“We are excited about the chance to work with Lilly in the effort to find an effective Alzheimer’s prevention therapy as soon as possible, introduce novel ways to increase the size, speed, and ease of participating in Alzheimer’s prevention trials, and do so in ways that might benefit the entire field,” said Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute and one of the trial’s lead investigators.

Donanemab, an antibody, is designed to recognize a harmful form of the beta-amyloid protein that clumps into toxic plaques in the brains of Alzheimer’s patients. By binding to this toxic form of beta-amyloid protein, donanemab works to trigger an immune response that helps to clear these plaques, which might slow disease progression.

Data from the TRAILBLAZER-ALZ study, a Phase 2 trial (NCT03367403), showed that donanemab was able to slow cognitive decline and the loss of daily life abilities when compared with a placebo, the study’s main goal. Donanemab was also able to clear amyloid plaques more effectively than placebo.

These findings supported the decision by the U.S. Food and Drug Administration to grant breakthrough therapy status to donanemab  as a potential Alzheimer’s treatment. This designation is intended to speed the development of therapies for serious medical conditions. It is given to candidate therapies that show a potential for significant improvement over already existing FDA-approved treatments.

Two other clinical trials — the long-term extension TRAILBLAZER-EXT (NCT04640077) study, and the global Phase 3 TRAILBLAZER-ALZ-2 (NCT04437511) study — are currently assessing the safety and efficacy of donanemab in patients with early Alzheimer’s.

TRAILBLAZER-ALZ-2 is enrolling up to 1,500 early stage patients, ages 60 to 85, experiencing gradual and progressive changes in memory for at least six months. People will be randomly assigned to donanemab or to a placebo, both given intravenously, for up to 76 weeks (about 1.4 years). More than 300 sites are recruiting across the U.S., Canada, Europe, Australia, and Japan; contact and other can be found here.

TRAILBLAZER-EXT is open to those who participated in previous donanemab studies.

“This collaboration combines Lilly’s more than 30 years of dedication to Alzheimer’s research with Banner’s unique expertise and showcases our collective commitment to partner within the health care community to find potential treatments to end this devastating disease,” said Mintun.