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Notable Approval: FDA Approves First At-home Starting Dose for Alzheimer’s Disease Treatment
The U.S. Food and Drug Administration (FDA) has approved a new starting dosage regimen for the subcutaneous (under the skin) formulation of Leqembi (lecanemab-irmb), an amyloid beta-directed antibody indicated for the treatment of adult patients with Alzheimer's disease. Previously approved only as an intravenous starting dosage, with the option for transitioning to intravenous or subcutaneous maintenance dosage after 18 months of treatment, this approval marks the first time patients can begin treatment with home administration by themselves or their caregiver.
Condition
Alzheimer’s disease is an irreversible, progressive brain disorder affecting more than 6.5 million Americans. The disease 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 the formation of amyloid beta plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections.
Data Supporting Leqembi
The effectiveness of Leqembi was tested in two large clinical trials (Study 1, NCT01767311; Study 2 NCT03887455) in patients with Alzheimer’s disease (patients with confirmed presence of amyloid pathology and mild cognitive impairment or mild dementia stage of disease). Both trials were randomized, placebo-controlled studies, meaning patients were randomly assigned to receive either Leqembi or a placebo (an inactive treatment), and neither the patients nor the researchers knew who received which treatment during the study.
In both studies, the dose evaluated was 10 mg/kg given once every two weeks by intravenous (IV) infusion — meaning the medication was delivered directly into a vein over a period of time at a clinic. This was studied over an 18-month treatment period, with an option for patients to continue in a longer-term follow-up phase.
- The subcutaneous formulation was not tested separately in large clinical outcome trials. Instead, its effectiveness is supported by two key findings:
The IV formulation's proven effectiveness in clinical trials.
- Evidence that the subcutaneous formulation produced equivalent results in the body and similar reductions in amyloid plaques as the IV formulation.
Safety Information
The most common side effects of Leqembi are headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA), a side effect known to occur with the class of antibodies targeting amyloid. ARIA most commonly presents as temporary swelling in areas of the brain seen on imaging studies that usually resolve over time and may be accompanied by small spots of bleeding in or on the surface of the brain. Although ARIA is often not associated with any symptoms, symptoms can occur and include headache, confusion, dizziness, vision changes and nausea. ARIA can also infrequently present with serious and life-threatening brain edema that can be associated with seizures and other severe neurological symptoms. Intracerebral hemorrhages can occur in patients treated with this class of medications and can be fatal. A boxed warning is included in the prescribing information to alert patients and caregivers to the potential risks associated with ARIA. Patients treated with Leqembi who are homozygous for the ApoE ε4 allele have a higher incidence of ARIA, including symptomatic, serious and severe ARIA, compared to heterozygotes and noncarriers. The prescribing information states that testing for ApoE ε4 status should be performed before starting treatment with Leqembi to inform the risk of developing ARIA.
Leqembi IQLIK is also associated with injection-related reactions, most of which are localized at the site of the injection, and can include redness, swelling, rash, pain, and/or bruising.
Use of anticoagulant medication was associated with an increased number of intracerebral hemorrhages in patients taking Leqembi compared to placebo. The prescribing information recommends caution when considering use of Leqembi in patients taking anticoagulants or with other risk factors for intracerebral hemorrhage.
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).
Designation
Leqembi received a Priority Review designation for this indication.
The approval was granted to Eisai Inc.
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