Large Clinical Trial Supports Alzheimer Drug Full Approval

Published on: 

FDA's approval of Leqembi paves the way for wider coverage of the drug by Medicare and establishes a process for further clinical testing and evaluation of treatments for this widespread, debilitating condition

FDA recently granted full, or traditional, approval to Eisai Pharmaceutical’s Alzheimer’s treatment Leqembi, converting an earlier conditional approval status with further data from a multi-regional study of nearly 1800 patients. Results indicated that the drug slows the rate of cognitive and functional decline in early Alzheimer’s patients, compared to placebo, but also raised certain safety concerns. The decision paves the way for wider coverage of the drug by Medicare and establishes a process for further clinical testing and evaluation of treatments for this widespread, debilitating condition.

Eisai and partner Biogen had gained FDA accelerated approval for the drug in January 2023 based on evidence from a Phase II study. However, reimbursement was limited by the earlier decision of the Centers of Medicare and Medicaid Services (CMS) to pay for Alzheimer’s drugs only for those patients enrolled in clinical trials to further test the safety and efficacy of the therapy. This approach utilized CMS’ Coverage with Evidence Development (CED) policy, which limits access to certain innovative medical products while clinical trials continue and is most commonly used for new medical devices. It was very unusual and controversial for CMS to curb coverage for a drug granted accelerated approval by FDA and reflects concerns about potentially huge outlays for Medicare on a therapy that may have limited efficacy and potential adverse effects.

Now with the sponsor presenting trial data supporting full FDA approval, CMS said it will provide appropriate, broader coverage for Leqembi. But reimbursement still will be contingent on physicians enrolling patients in registries so that CMS may track the effectiveness of the treatment and emergence of side effects going forward with broader patient use.

Study confirms effect


Eisai set the stage for FDA full approval by conducting a large Phase III placebo-controlled, double-blind, randomized study in North America, Europe, and Asia. Study 301 Clarity AD enrolled 1795 patients with early Alzheimer’s disease, as seen in measures of mild cognitive impairment or mild dementia stage disease. Half of the participants received treatment and half placebo, with further stratification based on severity of disease, use of other medications, geographical region, and evidence of relevant genetic markers.

FDA approval on July 6, 2023 was based on data from 18 months of treatment indicating that the drug may slow progression of Alzheimer’s symptoms, as measured on global cognitive and functional scales. An FDA advisory committee had voted on June 9, 2023 that study results verified clinical benefit of Leqembi for its indicated use. However, the treatment will carry a boxed warning alerting patients and prescribers to the potential risks for individuals experiencing amyloid-related imaging abnormalities (ARIA) that may be associated with headaches, dizziness, as well as more serious brain edema. FDA recommends testing for a certain genetic marker that may be related to this condition.

Utilization and prescribing of the drug are uncertain, as many questions remain to be addressed concerning long-term effectiveness and prevalence and severity of side effects. And while Medicare and insurers will pay for much of the proposed $26,000 a year drug cost, patients will be responsible for considerable cost-sharing for the therapy, as well as a range of clinical visits and tests. At the same time, the relatively small positive effect on patient health may deter prescribing until additional data emerges. Utilization also may rise in the future with the development of new formulations that don’t require such frequent infusion, and more advanced diagnostics may better identify patients most likely to benefit and less likely to suffer serious side effects from the drug.

About the author

Jill Wechsler is Washington reporter for BioPharm International.