With New Trial Data, Lecanemab Wins FDA Breakthrough Status

Based on new evidence from an ongoing Phase 2b clinical trial, the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to lecanemab, also called BAN2401, an investigational antibody for treating early Alzheimer’s disease.

The therapy, being developed jointly by Eisai and Biogen, is designed to slow Alzheimer’s progression.

The FDA’s decision was based on clinical evidence from Study 201, a Phase 2b (NCT01767311) trial that enrolled patients who had mild cognitive impairment or dementia and a confirmed presence of beta-amyloid — the protein that forms toxic clumps in Alzheimer’s — deposits in the brain.

With the breakthrough therapy status, the companies may be able to speed up the development of lecanemab for Alzheimer’s, as the therapy is now eligible for all fast-track designation benefits, as well as intensive guidance on an efficient development program. The designation grants eligibility for rolling review and potentially priority review

Lecanemab is an antibody that is administered directly into the bloodstream and is designed to specifically bind to a soluble, damaging version of the beta-amyloid protein. By binding to this form of beta-amyloid, lecanemab is thought to promote its clearance before it clumps and forms toxic plaques, this way slowing disease progression.

Results from Study 201 showed that, when given at the highest dose (10 mg/kg every other week), lecanemab reduced deposits of beta-amyloid in the brain and slowed clinical decline. However, the trial failed to meet its main goal. Specifically, lecanemab did not show that it had an 80% probability of being better than placebo, by 25%, at reducing patients’ ratings on the Alzheimer’s Disease Composite Score — a combined measure of cognitive abilities — after one year of treatment.

This led to the initiation of an open-label extension phase, in which both researchers and participants know what therapy, and at what dose, patients are receiving. In that phase, patients completing the core study could continue or start to receive the investigational therapy, all at the highest dose, for up to two years.

One-year preliminary findings showed that amyloid reductions in people treated with the highest dose in the core study were sustained after treatment discontinuation within the gap period before entering the extension phase. Notably, greater beta-amyloid drops were observed in those patients assigned to a placebo for the first part of Study 201 and who switched to lecanemab in the extension phase.

Lecanemab currently is also being evaluated in two ongoing Phase 3 trials: Clarity AD (NCT03887455) and AHEAD 3-45 (NCT04468659).

Clarity AD, which seeks to confirm the safety and efficacy of lecanemab given at 10 mg/kg every other week in people with early Alzheimer’s, completed its enrollment in March 2021 with 1,795 participants. The companies expect initial data by the end of September 2022.

Meanwhile, AHEAD 3-45 will evaluate the therapeutic effect of lecanemab on the progression of Alzheimer’s in patients who are clinically normal (asymptomatic) but have intermediate or elevated levels of beta-amyloid clumps in their brains. This trial is being conducted as a collaborative effort between Eisai and the Alzheimer’s Clinical Trial Consortium, and is funded by the National Institute on Aging, part of the National Institutes of Health. Participants are being recruited at more than 100 sites worldwide.