Eisai, a Tokyo-based pharmaceutical company, has received full FDA approval for its Alzheimer’s disease drug, Leqembi. This decision not only marks a significant milestone for the treatment of Alzheimer’s but also sets a precedent for the review and potential approval of other therapies for the neurodegenerative disorder. Leqembi is an antibody that targets the buildup of amyloid beta protein plaques in the brains of Alzheimer’s patients.
The FDA’s decision covers patients with mild cognitive impairment or mild dementia, which is the same population that was evaluated in the drug’s clinical testing. In January, Leqembi received accelerated approval based on a placebo-controlled Phase 2 study that enrolled 825 patients. The study showed a reduction in amyloid plaque in the brain after 12 months of treatment. This surrogate endpoint, which indicates that the drug may be working, was also the basis for the accelerated approval of Biogen’s Alzheimer’s drug, Aduhelm.
To confirm Leqembi’s efficacy, a Phase 3 study involving a larger group of 1,795 patients was conducted. The results showed a statistically significant 27% reduction in clinical decline compared to the placebo group, as measured by a scale used to evaluate dementia symptoms. This confirmatory study verified the drug’s safety and effectiveness in treating Alzheimer’s disease, making it the first drug to target the underlying disease process and demonstrate clinical benefit.
However, the drug’s approval comes with warnings about severe complications, including deaths reported during the confirmatory clinical trial. The side effects reported in the trial included potentially fatal swelling and bleeding complications known as amyloid-related imaging abnormalities (ARIA), which are a known risk associated with amyloid-targeting antibody drugs. Leqembi’s label now includes a black box warning, the strictest alert the FDA can issue, highlighting the risk of ARIA. The warning also mentions a higher risk of ARIA in patients who are carriers of the APOE4 gene, which increases the risk of Alzheimer’s.
During the Phase 3 study’s open-label extension, three deaths were attributed to brain bleeding complications, two of which occurred in patients using blood thinners while receiving Leqembi treatment. The drug’s label advises caution for patients taking anticoagulants. These risks were discussed during an FDA advisory committee meeting, where the committee unanimously confirmed the drug’s clinical benefit based on the Phase 3 data.
Leqembi is a product of a partnership between Eisai and Biogen, the same alliance that developed Aduhelm. Despite its FDA approval, Aduhelm faced challenges in the market due to concerns about its price, safety, and efficacy. The Centers for Medicare and Medicaid Services (CMS) only covered Aduhelm for Medicare beneficiaries enrolled in approved clinical trials, citing lingering safety and efficacy questions. However, CMS recently announced that it would cover Alzheimer’s drugs with full FDA approval and require physicians to participate in registries to collect real-world data on the drugs’ effectiveness and safety.
This coverage policy will also impact Eli Lilly’s amyloid-busting antibody drug candidate, donanemab, as it plans to seek full FDA approval based on Phase 3 data showing a 35% slowing in decline compared to placebo. The CMS registry will help gather evidence about the benefits and harms of these drugs in real-world community practice and how they may vary based on patient characteristics, treating clinicians, and settings.
