In January, 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 fundamental pathophysiology of the disease. According to the FDA, 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 Dr. Billy Dunn, 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.
Researchers evaluated Leqembi’s efficacy in a double-blind, placebo-controlled study of 856 patients with Alzheimer’s disease. Treatment was initiated in patients with mild cognitive impairment or mild dementia 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 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 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.
According to McKnight’s Long-Term Care News, neurologists in the U.S. have a strong interest in prescribing the Leqembi, with the majority of 73 specialists surveyed saying they would prescribe the treatment if the government fully approves it.
The March 2023 survey, from Spherix Global Insights, found that a healthy proportion of neurologists had already begun prescribing Leqembi within a month of commercial availability, while most have chosen to wait for the FDA’s decision when it reviews the request by Eisai, the drug’s manufacturer, for traditional approval on July 6. If traditional FDA approval is granted, nearly all of the surveyed specialists said they planned to prescribe the treatment, mostly within the year following the greenlight, Spherix reported.
The prescribing information for Leqembi includes a warning for amyloid-related imaging abnormalities (ARIA), which are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur. ARIA most commonly presents as temporary swelling in areas of the brain that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain, though some people may have symptoms such as headache, confusion, dizziness, vision changes, nausea, and seizure.
Another warning for Leqembi is for a risk of infusion-related reactions, with symptoms 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.
According to Fierce Pharma, while there is another new drug on the market for Alzheimer’s — Aduhelm, which Eisai helped create with Biogen — that drug is commercially non-viable at the moment.
Specifically, the Centers for Medicare & Medicaid Services refused to cover payments of Aduhelm, which was also damaged by the controversial way the FDA approved the drug in 2021. The drug passed the regulatory hurdle despite serious safety and efficacy questions, including from the FDA’s own drug-review experts, who denied its approval at the drug’s advisory committee and were overruled by the FDA itself several months later.