The FDA Peripheral and Central Nervous System Drugs Advisory Committee unanimously voted that lecanemab (leqembi) showed clinical benefit in early Alzheimer’s disease, paving the way for a traditional approval of the drug. This milestone comes just ahead of its July 6th PDUFA date and if approved, Leqembi will be the first-ever disease-modifying treatment for Alzheimer’s to receive full approval.
“We are encouraged by the FDA Advisory Committee’s decision to endorse Leqembi, but we recognize that the mission to develop effective treatments for all patients with Alzheimer’s disease is far from over,” says Dr. Howard Fillit, Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “While this is an exciting step forward, our understanding of the biology of aging tells us we will need multiple therapies that target novel pathways and can be used in combination with other drugs, like anti-amyloids, for a precision medicine approach.”
As more new therapies move from discovery to development, there is an increased need to develop and utilize complimentary biomarkers and diagnostic tools that can identify the populations that will most benefit from various treatments. One of the biomarkers that formed the basis for the accelerated approval of Leqembi is the Amyvid® PET scan, which received early seed funding from the ADDF, and has helped to enroll patients and monitor progress in several monumental clinical trials.
“Biomarkers offer the ability to match the right drugs to the right patients at the right time,” says Dr. Fillit. “As with other diseases of chronic aging, a precision prevention approach that begins with an early, accurate diagnosis and tailors drug combinations based on a patient’s individual biomarker profile will give us the best chance of slowing—and potentially stopping—disease progression.”
This milestone also underscores the recent progress made in the Alzheimer’s robust drug pipeline, demonstrating the field’s ability to run rigorous clinical trials that provide definitive answers on the effectiveness of new treatments with the support of biomarker monitoring.
“In today’s pipeline, over three quarters of drugs in clinical development are targeting novel pathways, priming the field for the next generation of drugs that target a whole host of underlying factors,” adds Dr. Fillit.
About The Alzheimer’s Drug Discovery Foundation (ADDF)
Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer’s Drug Discovery Foundation is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer’s disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer’s, employing a venture philanthropy model to support research in academia and the biotech industry. The ADDF’s leadership and contributions to the field have played a pivotal role in bringing the first Alzheimer’s PET scan (Amyvid®) and blood test (PrecivityAD®) to market, as well as fueling the current robust and diverse drug pipeline. Through the generosity of its donors, the ADDF has awarded more than $250 million to fund over 720 Alzheimer’s drug discovery programs, biomarker programs and clinical trials in 19 countries. To learn more, please visit: http://www.alzdiscovery.org/.
Why Leqembi for Alzheimer’s Won Unanimously
The unanimous decision by the panel of independent experts was based on the supplementary Biologics License Application (sBLA) which includes data from Eisai’s large global confirmatory Phase 3 Clarity AD trial. The Clarity AD trial met its prespecified primary endpoint, demonstrating a highly statistically significant slowing of cognitive and functional decline (27%, p=0.00005) compared to placebo over 18 months. Highly statistically significant treatment effects were also observed for all multiplicity-controlled secondary endpoints that examined cognition and functional changes using other validated scales. The most common adverse events (>10%) in the LEQEMBI group were infusion reactions (LEQEMBI: 26.4%; placebo: 7.4%), ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis: LEQEMBI: 17.3%; placebo: 9.0%), ARIA-E (edema/effusion: LEQEMBI: 12.6%; placebo: 1.7%), headache (LEQEMBI: 11.1%; placebo: 8.1%), and fall (LEQEMBl: 10.4%; placebo: 9.6%). Infusion reactions were largely mild-to-moderate (grade 1-2: 96%) and occurred on the first dose (75%). The results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
LEQEMBI, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril*) and insoluble forms of amyloid beta (Aβ), received accelerated approval on January 6, 2023, and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD. Its continued approval may be contingent upon verification of LEQEMBI’s clinical benefit in the confirmatory Clarity AD trial (Study 301). The advisory committee agreed unanimously that Study 301 verified the clinical benefit. The Prescription Drug User Fee Act (PDUFA) action date for the traditional approval is July 6, 2023.
Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
LEQEMBI has been approved under the FDA accelerated approval pathway. Click here for the Prescribing Information.