US Food and Drug Administration converts Leqembi to traditional approval following verification of clinical benefit.
Yesterday, the FDA converted Lecanemab – which will now be known by the brand name Leqembi – to traditional approval having decided that a confirmatory trial verified the drug’s clinical benefit. Indicated to treat adult patients with Alzheimer’s, Leqembi, which was developed by Japanese pharma company Eisai and US biotech Biogen, is the first amyloid beta-directed antibody to be converted from an accelerated approval to a traditional approval for the treatment of this devastating neurological disease.
The drug works by reducing amyloid plaques that form in the brain, a defining pathophysiological feature of the disease. While amyloid is a naturally-occurring protein, in Alzheimer’s, abnormal levels of the molecule clump together to form sticky, clumping plaques that collect between neurons and disrupt cell function.
Longevity.Technology: Leqembi was approved in January under the Accelerated Approval pathway. This pathway allows the FDA to approve drugs for serious conditions where there is an unmet medical need, based on clinical data demonstrating the drug’s effect on a surrogate endpoint. And there certainly is an unmet medical need for treatments for Alzheimer’s, as despite extensive research and advancements in medical science, this debilitating neurodegenerative disorder continues to affect millions of people worldwide.
Alzheimer’s causes progressive cognitive decline, memory loss and, ultimately, a loss of independence and quality of life. Existing treatments only provide modest symptomatic relief, failing to halt or reverse the underlying disease progression; there is an urgent need for breakthrough therapies that can address the complex mechanisms of Alzheimer’s disease and offer disease-modifying effects – only then will we begin to alleviate the tremendous burden on individuals, families and society as a whole.
In the case of Leqembi, its ability to reduce amyloid plaques in the brain meant it met the FDA’s requirement that it is reasonably likely to be of clinical benefit to patients. As a post-marketing requirement of the accelerated approval, the FDA required the applicant to conduct a clinical trial – often referred to as a confirmatory study – to verify the anticipated clinical benefit of Leqembi. Efficacy of Leqembi was evaluated using the results of Study 301 (CLARITY AD), a Phase 3 randomized, controlled clinical trial.
“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” said Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease .”
Study 301 was a multi-center, randomized, double-blind, placebo-controlled, parallel-group study that enrolled 1,795 patients with Alzheimer’s disease. Treatment was initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of amyloid beta pathology. Patients were randomized in a 1:1 ratio to receive placebo or Leqembi at a dose of 10 milligrams (mg)/kilograms (kg), once every two weeks. Leqembi demonstrated a statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the primary endpoint, the Clinical Dementia Rating Scale Sum of Boxes score, compared with placebo. Statistically significant differences between treatment groups were also demonstrated on all secondary endpoints, which included the Alzheimer’s Disease Assessment Scale Cognitive Subscale 14, and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment .
On 9th June, the FDA convened the Peripheral and Central Nervous System Drugs Advisory Committee to discuss whether Study 301 provided evidence of clinical benefit of Leqembi for the treatment of Alzheimer’s disease. All committee members voted that the results of the study did indeed verify the clinical benefit of Leqembi for the indicated use.
The most common side effects of Leqembi were headache, infusion-related reactions and amyloid-related imaging abnormalities (ARIA), a side effect known to occur with the class of antibodies targeting amyloid. Leqembi is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of its inactive ingredients. Adverse reactions may include angioedema (swelling) and anaphylaxis (allergic reaction).
The FDA statement says that Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease, the population in which treatment was studied in clinical trials .