Eisai Starting Rolling Submission to FDA for Lecanemab Approval
Eisai has started work on a rolling submission to the U.S. Food and Drug Administration (FDA) for a Biologics License Application (BLA) for lecanemab (BAN2401), its antibody treatment for early Alzheimer’s disease.
As a rolling submission, Eisai will submit each portion of its application as it is completed, rather than waiting for its entire package to be done before handing it over to federal regulators, as is normally the process.
“The lecanemab rolling BLA submission marks a new milestone toward the advancement of a treatment system for [Alzheimer’s disease],” Haruo Naito, Eisai’s CEO, said in a press release.
“As part of our human health care mission, we are committed to bringing new medicines to people living with [Alzheimer’s] and their families as early as possible,” Naito said.
Lecanemab, being jointly developed by Eisai and Biogen, is an investigational antibody administered directly into the bloodstream that is designed to specifically bind to a soluble, damaging version of the beta-amyloid protein — which clumps and builds up into toxic plaques in Alzheimer’s disease
By binding to this form of beta-amyloid, lecanemab may promote its clearance before it can create the deposits that are a key hallmark of Alzheimer’s disease. This is thought to slow disease progression in people with early Alzheimer’s.
In June, the FDA granted lecanemab breakthrough therapy status, a designation that helps expedite the advancement of medications for serious and life-threatening conditions. With that, the therapy is now eligible for all fast-track benefits, and potentially priority review.
Once all portions of the application have been submitted, and the BLA is accepted, a Prescription Drug User Fee Act (PDUFA) date can be set. That date — for the completion of the agency’s examination — is known as the FDA action date.
This rolling submission agreement for lecanemab was based mostly on clinical evidence from Study 201, a Phase 2b (NCT01767311) trial that enrolled 856 patients who had mild cognitive impairment or dementia and a confirmed presence of beta-amyloid deposits in the brain.
The results showed that, after 18 months of treatment on the highest dose (10mg/kg every other week) of lecanemab, brain amyloid was reduced, and more than 80% of participants became amyloid negative by visual reads.
Additionally, this reduction in amyloid was correlated with a slower clinical decline on different scales that measure cognitive ability in people with Alzheimer’s. Specifically, the researchers used the Alzheimer’s Disease Composite Score or ADCOMS, the Clinical Dementia Rating-Sum-of-Boxes, known as CDR-SB, and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale or ADAS-cog.
The rate of amyloid-related imaging abnormalities-edema/effusion (ARIA-E) — fluid accumulation in the brain often associated with therapies that target amyloids — was 9.9% for the highest dose.
However, the trial failed to meet its main goal. Specifically, lecanemab did not show that it had an 80% probability of being better than a placebo, by 25%, at reducing patients’ ratings on the ADCOMS after one year of treatment.
This led to the launch of an open-label extension phase, in which all participants who completed the core study could continue or start receiving the investigational therapy, all at the highest dose, for up to two years.
One-year preliminary findings showed that lecanemab treatment resulted in significant reductions in amyloid readings as early as three months, with more than 80% of participants achieving amyloid negative status by visual read.
Amyloid reductions in those treated with the highest dose in the main study were maintained after discontinuing treatment in the period before entering the extension phase. Also, patients who were assigned to receive a placebo in Study 201 and were then switched to lecanemab in the extension phase showed the greatest drops in beta-amyloid levels.
The rate of ARIA-E was consistent with that of the core study, and was observed in about 10% of participants.
Lecanemab now is being tested in two ongoing Phase 3 trials: Clarity AD (NCT03887455) in early Alzheimer’s and AHEAD 3-45 (NCT04468659) in asymptomatic individuals who have intermediate or elevated levels of beta-amyloid clumps in their brains.
The FDA has agreed that, upon completion, the results of Clarity AD can serve as the confirmation study to verify the clinical benefits of lecanemab. The blinded safety data from the Clarity AD study will be able to be included to support the BLA.
“It is our vision that patients and their families have choice and access to multiple treatment options for Alzheimer’s disease,” said Michel Vounatsos, CEO at Biogen, who called the rolling submission “a positive step toward that goal.”
“We believe that treatments directed at amyloid beta reduction in the brain have the potential to transform diagnosis and treatment of Alzheimer’s disease,” Vounatsos said. “We look forward to continuing to work with Eisai to pioneer science, advance knowledge, and serve the needs of Alzheimer’s patients.”
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