Lecanemab for Early Alzheimer’s Granted the FDA’s Fast Track Status
Lecanemab, an investigational antibody also known as BAN2401, has been granted a fast track designation from the U.S. Food and Drug Administration (FDA), which may help speed up its development for the treatment of early Alzheimer’s disease.
The antibody, developed jointly by Biogen and Eisai, is designed to bind to the protein amyloid-beta. This potentially allows the immune system to clear the protein before it forms the toxic clumps that drive the death of nerve cells (neurons) in the brains of those with Alzheimer’s.
The FDA granted its breakthrough therapy designation to lecanemab in mid-2021. In September, Eisai started a rolling submission for a biologics license application under the FDA’s accelerated approval pathway, which the company expects to complete during the first half of 2022, according to a press release. A rolling submission means that the company can submit sections of its application for review as soon as they are completed, rather than waiting until every section is ready before the entire application can be reviewed.
The biologics license application is based on data from Study 201, a Phase 2b clinical trial (NCT01767311) that enrolled 856 patients with mild cognitive impairment or dementia and a confirmed presence of amyloid-beta clumps in the brain.
The data showed that lecanemab reduced amyloid-beta clumps in the brain and slowed clinical decline. The link between the two supports the use of amyloid-beta as a surrogate marker that could allow quicker approval of lecanemab for early Alzheimer’s. A surrogate marker is not itself a true indicator of clinical benefit but could be used to predict how well a therapy may work. Its use might shorten the time required for the therapy to receive approval by the FDA.
Under the accelerated approval program, the FDA also requires lecanemab to be tested in a confirmatory clinical trial to verify that the therapy provides the clinical benefit shown in earlier-phase studies — this time in more patients.
A Phase 3 clinical trial (NCT03887455), called Clarity AD, is testing the safety and efficacy of lecanemab given at 10 milligrams per kilogram of body weight (mg/kg) every two weeks versus a placebo in up to 1,795 patients with early Alzheimer’s.
The FDA has agreed that Clarity AD can serve as the confirmatory trial to verify the clinical benefit of lecanemab. The study is expected to finish in March 2024, with initial data out by the end of September this year. Meanwhile, its safety data are included in the ongoing rolling submission.
The primary endpoint of the 18-month study, to be followed by an open-label extension phase, is a change from an initial measurement in the Clinical Dementia Rating–Sum of Boxes, a clinical tool for staging dementia. One of its secondary endpoints is a change in the levels of beta-amyloid measured on a position emission tomography scan.
Another Phase 3 clinical study (NCT04468659), called AHEAD 3-45, is testing the efficacy of lecanemab versus a placebo in up to 1,400 patients with preclinical Alzheimer’s disease and intermediate or high levels of beta-amyloid.
In a new Phase 1 clinical trial (NCT05045716), Eisai will study the bioavailability (the amount of medication that enters circulation) and pharmacokinetics (the activity of the medication over time in the body) of lecanemab when given subcutaneously, or under the skin, in up to 50 healthy individuals. The company is currently recruiting participants.