FDA Grants Accelerated Approval for Leqembi



Last updated 3/8/2023 at 11:27pm | View PDF

On January 6, the U.S. Food and Drug Administration approved Leqembi (lecanemab-irmb) via the Accelerated Approval pathway for the treatment of Alzheimer’s disease.

Leqembi is the second of a new category of medications approved for Alzheimer’s disease that target the basic pathophysiology of the disease. These medications represent an important advancement in the ongoing fight to effectively treat Alzheimer’s disease.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” said Billy Dunn, M.D., director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”

Alzheimer’s disease is an irreversible, progressive brain disorder affecting more than 6.5 million Americans that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks. While the specific causes of Alzheimer’s are not fully known, it is characterized by changes in the brain — including amyloid beta plaques and neurofibrillary, or tau, tangles — that result in loss of neurons and their connections. These changes affect a person’s ability to remember and think.

Leqembi was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. The results of a Phase 3 randomized, controlled clinical trial to confirm the drug's clinical benefit have recently been reported and the agency anticipates receiving the data soon.

"This treatment is the second Alzheimer’s drug to be approved that targets the amyloid plaques in the brain that are thought to cause Alzheimer’s Disease," said Dr. Karen Haught, public health officer for Tulare County, "but it is the first drug to show clinical differences relative to placebo in its prespecified end points. Unlike its predecessor, Aducanumab, the Accelerated Approval Program that approved Leqembi based on its ability to reduce amyloid plaques is also supported by a modest slowing of the progression of the disease in individuals with mild cognitive impairment or early Alzheimer’s.

"There are no effectiveness data on initiating treatment at earlier or later stages of the disease," she continued. "As a result, this medication is only indicated for mild dementia. This approval pathway has been used for treatments for life-threatening conditions when there is not currently an alternative treatment option. After the approval, the FDA is requiring larger and more long-term clinical trials to further address safety and efficacy. We look forward to the findings of these additional trials."

Researchers evaluated Leqembi’s efficacy in a double-blind, placebo-controlled, parallel-group, dose-finding study of 856 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 receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque, with patients receiving the approved dose of lecanemab, 10 milligram/kilogram every two weeks, having a statistically significant reduction in brain amyloid plaque from baseline to Week 79 compared to the placebo arm, which had no reduction of amyloid beta plaque.

These results support the accelerated approval of Leqembi, which is based on the observed reduction of amyloid beta plaque, a marker of Alzheimer’s disease. Amyloid beta plaque was quantified using positron emission tomography (PET) imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions expected to be widely affected by Alzheimer’s disease pathology compared to a brain region expected to be spared of such pathology.

Possible Side Effects

"A possible side effect of this class of drugs is Amyloid-related imaging abnormality (ARIA)," said Dr. Haught. "Although, individuals who are diagnosed with ARIA usually are asymptomatic, in some cases clinical symptoms may occur. Of note swelling and bleeding of the brain may occur.

"As a result, patients on this medication must receive periodic brain imaging. For this reason, it is important to talk with your doctor about your own personal risk factors for these and other potential side effects. Another discussion to have with your care provider is cost of Leqembi.

"At this time, it is still not clear whether Medicare and private health insurers will cover this medication, however, there may be patient assistance programs available from the manufacturers for eligible uninsured and underinsured patients. We all hope for a safe and effective treatment to help our loved ones and their families affected by Alzheimer’s Disease."

Another warning for Leqembi is for a risk of infusion-related reactions, such as flu-like symptoms, nausea, vomiting and changes in blood pressure. The most common side effects of Leqembi were infusion-related reactions, headache and ARIA.

As specified in the prescribing information, Leqembi is for the treatment of Alzheimer’s disease. The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.

The labeling also states that there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.

The approval of Leqembi was granted to Eisai R&D Management Co., Ltd.


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