Alzheimer’s disease is an irreversible, progressive brain disorder. It slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks. Even though the precise origins of Alzheimer’s are not entirely understood, it is known that abnormalities mark the disease in the brain, such as amyloid beta plaques and neurofibrillary, or tau, tangles, which lead to the loss of neurons and the connections they form. These changes have an impact on a person’s memory and thought processes.
On January 6, 2023, the U.S. Food and Drug Administration approved Leqembi (lecanemab-irmb) via the Accelerated Approval pathway to treat Alzheimer’s disease. Leqembi is an amyloid beta-directed antibody that is thought to work by selectively binding to neutralize and eliminate amyloid-beta (Aβ) aggregates that contribute to the progressive loss of neurons in Alzheimer’s disease.
It is the second of a new category of medications approved for Alzheimer’s disease that target the fundamental pathophysiology of the disease.
Leqembi was approved through the FDA’s accelerated approval process, which allows it to do so for medications of severe conditions when there is an unmet medical need, and the medication is demonstrated to have an impact on a surrogate endpoint that is reasonably likely to predict a clinical benefit for patients.
Billy Dunn, M.D., director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said, “Alzheimer’s disease immeasurably hinders the lives of those who suffer from it and has devastating effects on their loved ones. 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.”
Researchers assessed Leqembi’s effectiveness in a double-blind, placebo-controlled, parallel-group study with 856 Alzheimer’s patients. The treatment was started after amyloid beta pathology was confirmed in patients with mild cognitive impairment or mild dementia.
Patients receiving the recommended dose of lecanemab, 10 milligram/kilogram every two weeks, had a statistically significant reduction in brain amyloid plaque from baseline to Week 79 compared to the placebo arm, which had no reduction in amyloid beta plaque. Patients receiving the treatment had a significant dose- and time-dependent reduction of amyloid beta plaque.
These findings support Leqembi’s expedited approval, which is justified by the reported decline in amyloid-beta plaque levels, a sign of Alzheimer’s disease. To compare the levels of amyloid beta plaque in a composite of brain regions expected to be severely affected by the pathology of Alzheimer’s disease to a brain region expected to be spared from such pathology, an amyloid-beta plaque was quantified using positron emission tomography (PET) imaging.
Leqembi comes with a warning for amyloid-related imaging abnormalities (ARIA), which are known to happen when using antibodies from this class. Despite the rarity of major and life-threatening incidents, ARIA typically does not show symptoms.
Another warning for Leqembi is the 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.