Eisai Completes Rolling Submission to FDA for Lecanemab Approval

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Eisai has completed a rolling submission to the U.S. Food and Drug Administration (FDA) to seek approval for lecanemab (BAN2401), an investigational antibody for the treatment of early Alzheimer’s disease accompanied by beta-amyloid deposits in the brain.

The request — made in the form of a biologics license application (BLA) — if accepted by the FDA will be reviewed under the agency’s accelerated approval pathway, which allows for earlier approval of therapies to treat serious conditions and fill an unmet medical need.

Eisai also has requested the FDA use its priority review, according to a press release from BioArctic, lecanemab’s co-developer together with Eisai and Biogen.

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If the BLA is accepted, the FDA will then announce a Prescription Drug User Fee Act (PDUFA) date, which authorizes the agency to collect fees from companies to expedite therapies’ approval process.

“I am impressed by our colleagues at Eisai and their diligent work to help patients and caregivers living with Alzheimer’s disease. The completion of the rolling submission is an important milestone to potentially providing new treatment options, and I am proud of the BioArctic coworkers who made their contribution to making this possible,” said Gunilla Osswald, BioArctic’s CEO.

The BLA was based mostly on clinical data from Study 201, a Phase 2b (NCT01767311) trial that enrolled 856 people with early Alzheimer’s, which include patients with mild cognitive impairment or dementia and a confirmed presence of beta-amyloid deposits in the brain, a disease hallmark.

Additional safety and biomarker data from an open-label extension phase study (180 patients) and blinded safety data from the ongoing Clarity AD Phase 3 trial (NCT03887455) were also included.

Results from Study 201 showed that treatment with the highest dose of lecanemab (10mg/kg every other week) led to marked reduction in brain amyloid deposits after 18 months. Moreover, over 80% of patients became amyloid-negative by visual reads.

The decrease in amyloid deposition was accompanied by a slower clinical decline on different scales that measure cognitive ability in people with Alzheimer’s.

Only a fraction of patients (9.9%) on the highest dose developed amyloid-related imaging abnormalities-edema/effusion (ARIA-E), a side effect associated with therapies that target amyloids that causes fluid accumulation in the brain.

The trial, however, failed to meet its main goal, which was to demonstrate it had an 80% probability of being better than a placebo.

This prompted a follow-up open-label extension phase where participants who completed Study 201 continued or began receiving lecanemab, all at the highest dose, for up to two years.

Preliminary data collected after one year showed that the investigational therapy led to a significant drop in amyloid readings as early as three months. Over 80% of participants were amyloid-negative status by visual read. The reduction in beta-amyloid deposits was also seen in patients who received a placebo in the first trial.

Data from the ongoing Clarity AD Phase 3 trial, which enrolled 1,795 patients, will serve as confirmation of the clinical benefits of lecanemab. The results are expected by fall and, if positive, they may support a request for the full approval of lecanemab to the FDA by March 2023.

Lecanemab targets a soluble, damaging version of the beta-amyloid protein. The antibody, administered directly into the bloodstream, was designed to clear beta-amyloid before it clumps together into beta-amyloid plaques. This is thought to slow disease progression in people with early Alzheimer’s.

The FDA gave lecanemab fast track and breakthrough therapy status, which help to speed its development.

Eisai has also started the process of seeking approval of lecanemab to treat early Alzheimer’s disease in Japan. Based on the data from the Clarity AD, the company will seek manufacturing and marketing approval of lecanemab in the U.S., Japan, and European Union by March 2023.