CHMP Gives Positive Opinion for Lecanemab Following Re-Examination of Data

Christopher van Dyck, MD

Months after the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) gave a negative opinion for the approval of lecanemab (Leqembi; Eisai), an antiamyloid treatment for early-stage Alzheimer disease (AD), the agency has flipped course, adopting a positive opinion for recommending approval.¹

Following the EMA’s regulatory process, the European Commission is expected to make a final decision on lecanemab’s marketing authorization application (MAA) within 67 days after receiving the CHMP’s recommendation. Lecanemab, a monoclonal antibody that selectively binds to soluble amyloid-ß (Aß) aggregates, has been on the market in the US since 2023 after gaining traditional approval from the FDA.

The medication’s positive opinion from the CHMP was primarily based on data from the phase 3 Clarity AD trial (NCT03887455), the same study it was traditionally approved on in the U.S. In this global, placebo-controlled, double-blind, parallel-group study, lecanemab met its primary end point of change in Clinical Global Dementia-Sum of Boxes (CDR-SB) score over an 18-month period relative to placebo. The large-scale study randomized 1795 patients with early AD, of which 1521 were in the recommended indicated population (apolipoprotein [APOE] ε4 non-carriers or heterozygotes).²

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Led by Christopher van Dyck, MD, director of the Yale Alzheimer’s Disease Research Center, treatment with lecanemab led to a statistically significant 27% reduction in CDR-SB compared with placebo over the 18-month period. Lecanemab also met secondary endpoints, showing a significant reduction in amyloid PET centiloids (LS difference: –50.12; P < .0001) and improved scores on the Alzheimer’s Disease Assessment Scale-Cognitive 14 (LS difference: –1.442; P = .00005) compared to placebo over 18 months. It further outperformed placebo on the Alzheimer's Disease Composite Scale (ADCOMS; LS difference: –0.00; P = .00002) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS MCI-ADL; LS difference: 2.016; P < .00001). Specifically, it slowed disease progression by 24% on ADCOMS and by 37% on ADCS MCI-ADL at the same time point.

Lecanemab is also approved in several other countries outside the U.S., including Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain. While several countries have integrated the therapy, some are still skeptical. Last month, the Therapeutic Goods Administration, the medicine and therapeutic regulatory agency of the Australian Government, made the decision not to register lecanemab for the treatment of early-stage AD, noting that the efficacy of the drug did not outweigh the safety risks associated with its use. In their decision, the agency stated that the reduction in disease progression observed in lecanemab-related trials was not significant enough to provide meaningful clinical benefit for patients.³

Since its approval, Eisai has tried to find new alternative ways to better administer and dose patients with the agent. In June, the FDA accepted the company’s supplemental biologics license application (sBLA) for a new monthly intravenous maintenance dosing option of the medication. The agency has until January 25, 2025, to give an answer.⁴ Earlier this month, Eisai submitted its BLA for a subcutaneous autoinjector formulation of lecanemab, which may allow for a more convenient method of administration for patients at home or at medical facilities. In an analysis of Clarity AD, treatment with subcutaneous lecanemab demonstrated greater amyloid plaque removal compared with biweekly intravenous administration, its approved regimen, with bioequivalence in pharmacokinetic exposure.⁵

REFERENCES
1. Eisai Receives Positive Opinion from the CHMP in the European Union for Lecanemab in Early Alzheimer's Disease. News release. Eisai. November 14, 2024. Accessed November 15, 2024. https://www.prnewswire.com/news-releases/eisai-receives-positive-opinion-from-the-chmp-in-the-european-union-for-lecanemab-in-early-alzheimers-disease-302306160.html
2. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948
3. TGA’s decision to not register lecanemab (Leqembi). Australian Government: Therapeutic Goods Administration. News release. October 16, 2024. Accessed November 15, 2024. https://www.tga.gov.au/news/news/tgas-decision-not-register-lecanemab-leqembi
4. FDA Accepts Eisai's Filing of LEQEMBI® (lecanemab-irmb) Supplemental Biologics License Application for IV Maintenance Dosing for the Treatment of Early Alzheimer's Disease. Eisai. June 9, 2024. Accessed November 15, 2024. https://www.prnewswire.com/news-releases/fda-accepts-eisais-filing-of-leqembi-lecanemab-irmb-supplemental-biologics-license-application-for-iv-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302167814.html
5. Eisai Completes Rolling Submission to US FDA for LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease Under the Fast Track Status. Eisai. October 31, 2024. Accessed November 15, 2024. https://www.prnewswire.com/news-releases/eisai-completes-rolling-submission-to-us-fda-for-leqembi-lecanemab-irmb-biologics-license-application-for-subcutaneous-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-under-the-fast-track-status-302293541.html