Eisai Starting Process of Requesting Lecanemab’s Approval in Japan

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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Eisai has started submitting data to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in support of an application for approval of its investigational lecanemab (BAN2401) to treat early Alzheimer’s disease.

This submission followed the company’s prior assessment consultation with the PMDA, given in advance of an approval application and intended to accelerate its review by identifying and addressing potential concerns, Eisai stated in a press release.

Lecanemab is an investigational antibody, being co-developed with Biogen, given as an intravenous (IV) infusion. It is designed to bind to a soluble, harmful version of the beta-amyloid protein, which clusters and accumulates into toxic plaques in the brains of those with Alzheimer’s, damaging and killing nerve cells (neurons).

By binding to beta-amyloid, lecanemab is thought to allow the immune system to eliminate this protein before it forms toxic clusters. This potentially could slow disease progression in people with in early disease stages.

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After the company’s request for a prior assessment was agreed to, Eisai submitted preclinical study data to the Japanese agency.

Eisai will now send additional data, including findings from its Phase 3 Clarity AD (NCT03887455) study, a confirmatory trial. Clarity AD is evaluating the safety and efficacy of lecanemab, given at 10 mg/kg every two weeks, against a placebo in up to 1,766 patients with mild cognitive impairment due to Alzheimer’s or mild Alzheimer’s dementia.

The primary goal of the 18-month study, being followed by an open-label extension phase, is a change from starting measures in the Clinical Dementia Rating–Sum of Boxes, a clinical tool for staging dementia. Changes in beta-amyloid levels as determined via a position emission tomography scan is a secondary goal.

Early study results are expected to be released in the fall. Based on these findings, Eisai plans to apply for marketing approval in Japan.

Eisai also started a rolling submission to the U.S. Food and Drug Administration (FDA) in September 2021 for lecanemab’s approval, which the company expects to complete this year. A rolling submission means the company can submit parts of its application for review as they come ready, rather than waiting until every section is complete and the whole application can be reviewed.

This rolling submission was supported by data from the ongoing Study 201, a Phase 2b (NCT01767311) trial in 856 patients with mild cognitive impairment or Alzheimer’s dementia and a confirmed presence of beta-amyloid clusters in the brain.

Reported results at one year into its long-term extension showed treatment with lecanemab reduced beta-amyloid clusters in the brain and slowed clinical decline in early-stage patients. This association could support the use of beta-amyloid as a surrogate marker. A surrogate marker does not necessary indicate the clinical benefit of a therapy but could be used to predict its efficacy. Its use could speed a treatment’s review by the FDA.

Eisai’s application to the FDA was accepted under its accelerated approval program, which requires lecanemab to be assessed in a larger, confirmatory study to verify treatment benefits seen in earlier clinical studies.

Lecanemab is also in a Phase 3 clinical study (NCT04468659), called AHEAD 3-45, in people ages 55 to 80 with preclinical Alzheimer’s disease, meaning they are clinically normal, and intermediate or elevated levels of beta-amyloid protein in the brain as evidenced on a PET scan or in their cerebrospinal fluid or blood plasma. Those ages 55 to 64 without elevated levels in such tests need to have a first-degree relative with dementia onset before age 75 or the ApoE4 gene variant, a known Alzheimer’s risk factor.

AHEAD 3-45 is currently recruiting up to 1,400 patients at sites across the U.S., Australia, Canada, Japan, and elsewhere in Europe and in Singapore. Those enrolled are being randomly assigned to lecanemab, given every two or four weeks, or to a matching placebo infusion.

The FDA also gave the potential therapy fast track status, which helps to speed its development.

A Phase 1 clinical trial (NCT05045716) in up to 60 healthy adults evaluated the bioavailability (the part of a therapy that reaches circulation) and pharmacokinetics (the movement of a medicine into, through, and out of the body) of a single dose of lecanemab given as a subcutaneous, or under the skin, injection.