FDA Requires Fast Track Designation for Subcutaneous Formulation of Leqembi for Alzheimer's Disease

The US Food and Drug Administration (FDA) has informed lecanemab-irmb (US brand name: Leqembi®) developers Eisai Co Ltd and Biogen Inc that a Fast Track designation specific to the subcutaneous formulation of the drug is necessary to proceed with rolling review. Eisai announced in February that its goal was to have treated 10,000 patients with lecanemab by the conclusion of its fiscal year in March 2024. However, as of January 26, only 2000 patients in the United States were undergoing treatment with this amyloid-busting antibody.

The latest notification by the FDA alters the course of Eisai's regulatory submission plans for lecanemab in the treatment of early Alzheimer disease. Initially, Eisai had aimed to submit a Biologics License Application (BLA) for weekly maintenance therapy via subcutaneous administration in March 2024. However, the FDA's recent requirement for additional 3-month immunogenicity data at the proposed maintenance dose of 360 mg weekly prompted Eisai to plan a rolling BLA submission. Following this, the FDA notified Eisai of the necessity for a Fast Track designation specific to the subcutaneous formulation to proceed with rolling review. Eisai has submitted a request for Fast Track designation, and the decision is expected within 60 days of the March 2024 submission.

Analysts from William Blair stated, “These are technicalities in our view and do not undermine the potential of Leqembi. But they are disappointing delays for Biogen, which clearly needs to demonstrate better execution to improve investor sentiment.” This development underscores the shifting regulatory landscape surrounding lecanemab's pathway to approval for the treatment of Alzheimer disease. A non-subcutaneous formulation of the drug received traditional FDA approval for the treatment of Alzheimer disease in July 2023, making it the first amyloid beta-directed antibody for the treatment of Alzheimer disease treatment to transition from accelerated to traditional approval.

The FDA's decision to grant traditional approval stemmed from the outcomes of a confirmatory trial, which substantiated the drug's clinical benefits. Initially, lecanemab received accelerated approval from the FDA in January 2023 and received unanimous endorsement for its clinical benefit and efficacy from an FDA Advisory Committee in June 2023. Helen Lavretsky, MD, MS, commented on the FDA approval of lecanemab, stating, “The FDA approval of lecanemab is an important milestone for millions of those suffering from mild to moderate Alzheimer’s disease and their families that will allow the disease-modifying drug to delay the progression of Alzheimer’s disease by 6 months or longer.”