FDA Accepts BLA for Lecanemab in Alzheimer Disease, Sets PDUFA Date for January 2023

Gunilla Osswald

After officially submitting it this May, the FDA announced they have accepted and granted priority review to Eisai and Biogen’s biologics license application (BLA) of lecanemab (BAN2401), an investigational agent to treat mild cognitive impairment (MCI) because of Alzheimer disease (AD). The companies have been given a Prescription Drug User Fee Act (PDUFA) action date of January 6, 2023.¹

Submitted under the accelerated approval pathway—the same pathway that Biogen’s aducanumab (Aduhelm) was approved under in 2021—the application was supported by data from the phase 2b proof-of-concept clinical trial, known as Study 201 (NCT01767311). Additionally, the FDA will consider and review results from the ongoing phase 3 Clarity AD study (NCT03887455), which will serve as complimentary data to verify the clinical benefit of lecanemab post approval. Dependent upon the results of Clarity AD, Eisai will submit for traditional approval of lecanemab to the FDA before the end of the first quarter in 2023.

Lecanemab, an antiamyloid beta (Aß) protofibril antibody, is designed to neutralize and eliminate soluble toxic Aß aggregates that are thought to contribute to the neurodegenerative process in AD. Study 201, a Bayesian design clinical trial, randomized 856 patients with early AD with a confirmed presence of amyloid pathology to lecanemab at multiple doses (2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, 10 mg/kg biweekly) or placebo, identifying 10 mg/kg biweekly as the effective dose achieving at least 90% of the maximum treatment effect.

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At the end of the 18-month treatment period, 10-mg/kg biweekly lecanemab reduced brain amyloid by a mean of 0.306 standardized uptake value ratio (SUVr) units from a baseline mean of 1.37. Additionally, this treated group had a 76% probability of achieving 25% less decline on the primary end point, the change on the Alzheimer Disease Composite Score (ADCOMS), than placebo. Developed by Eisai, ADCOMS combines items from the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog), Clinical Dementia Rating (CDR), and the Mini-Mental State Examination scales to enable a sensitive detection of changes in clinical functions of early AD symptoms and changes in memory.²

In conventional analyses, treatment with lecanemab 10 mg/kg biweekly resulted in a dose-dependent reduction in change from baseline in ADCOMS over 18 months, with 30% (P = .034) less decline than placebo. Additionally, a 26% less decline on CDR-sub of boxes was observed in the same dosed group (P = .125), along with a 47% less decline on ADAS-Cog scales as well. Amyloid-related imaging abnormalities-edema/effusion, a concern for patients with AD, was found in 9.9% of patients on 10 mg/kg biweekly dosing in Study 201.

Additionally, in April, data published using the AD Archimedes condition-event (ACE) disease stimulation model, the investigational agent was estimated to slow the rate of disease progression, resulting in an extended duration of MCI because of AD and mild AD dementia and shortened duration in moderate and severe AD dementia. Compared with standard of care alone, the proportion of patients treated with lecanemab plus standard of care who progressed to mild AD, moderate AD, and severe AD were reduced by 7%, 13%, and 10%, respectively. The model also predicted a 25% lifetime probability of needing institutional care for those who received the combination of treatments compared with 31% for standard care.³

BioArctic, a Swedish research-based biopharma company that signed off the rights for lecanemab in 2007, will be awarded a milestone payment of MEUR 15 from Eisai as a result of the accepted BLA. "For almost 20 years now, BioArctic's vision has been to develop innovative medicines for people with neurological disorders such as Alzheimer's disease, a disease which affects millions of people around the world. FDA's acceptance of the BLA and granting of a priority review for lecanemab brings us one step closer in our quest to meet the huge medical need in this patient population," Gunilla Osswald, chief executive officer, BioArctic, said in a statement.¹

REFERENCES
1. The FDA accepts BLA and grants priority review for lecanemab for treatment of early Alzheimer disease under the accelerated approval pathway. News release. Biogen / Eisai. July 6, 2022. Accessed July 6, 2022. https://www.biospace.com/article/releases/the-fda-accepts-bla-and-grants-priority-review-for-lecanemab-for-treatment-of-early-alzheimer-s-disease-under-the-accelerated-approval-pathway/
2. Swanson CJ, Zhang Y. Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer disease with lecanemab, an anti-Aß protofibril antibody. Alzheimers Res Ther. 2021;13(80). doi:10.1186/s13195-021-00813-8
3. Monfared AT, Tafazzoli A, Ye W, Chavan A, Zhang Q. Long-term health outcomes of lecanemab in patients with early Alzheimer’s disease using simulation modeling. Neurol Ther. 2022;11:863-880. doi:10.1007/s40120-022-00350-y