The Medicines and Healthcare products Regulatory Agency (MHRA) has granted approval for the use of lecanemab, marketed as Leqembi, as a treatment for early-stage Alzheimer’s disease. This decision, announced on 22 August 2024, marks a significant milestone as lecanemab is the first medicine in Great Britain that has demonstrated efficacy in slowing the progression of this debilitating condition.
The approval follows a thorough evaluation by the MHRA, supported by expert advice from the Commission on Human Medicines (CHM), the UK government’s independent advisory body. Julian Beach, Interim Executive Director for Healthcare Quality and Access at the MHRA, stated, “Licensing medicines that meet the necessary standards of safety, quality, and efficacy is a priority for us. We are confident that the regulatory standards for this medicine have been met.”
Lecanemab, a monoclonal antibody, works by targeting amyloid beta, a protein that forms harmful plaques in the brains of Alzheimer’s patients. By binding to these plaques, lecanemab reduces their presence, thereby slowing the disease’s progression. The treatment is administered via a 10mg/kg intravenous dose every two weeks, with each session lasting approximately one hour, under the supervision of a healthcare professional.
However, the approval comes with specific conditions. Lecanemab is approved for use in adults in the early stages of Alzheimer’s disease who have one or no copies of the apolipoprotein E4 (ApoE4) gene—a genetic marker associated with an increased risk of developing Alzheimer’s. The MHRA’s decision was influenced by clinical trial data involving 1,795 participants, which indicated that patients with two copies of the ApoE4 gene, known as homozygous patients, faced a higher risk of developing Amyloid Related Imaging Abnormalities (ARIAs). These abnormalities include temporary brain swelling (ARIA-E) and small brain haemorrhages (ARIA-H). While most ARIA events were asymptomatic, some patients did experience serious symptoms.
In light of these findings, the CHM advised that the benefit-risk ratio of lecanemab was favourable for ApoE4 non-carriers and heterozygous individuals (those with one copy of the gene) but not for homozygous patients. Consequently, testing for the ApoE4 gene is recommended before commencing treatment. Additionally, the use of lecanemab is contraindicated for patients on anticoagulants or those diagnosed with cerebral amyloid angiopathy (CAA), as the risks outweigh the potential benefits.
The approval is accompanied by a commitment to closely monitor the safety of lecanemab. A controlled post-authorisation safety study will be conducted to assess the long-term safety and efficacy of the drug, particularly concerning ARIAs and intracerebral haemorrhage. A central registration system will also be implemented as part of a controlled access programme to ensure the responsible use of the medicine.
The most common side effects observed during the clinical trials were infusion-related reactions, headaches, and ARIAs. Despite these risks, lecanemab represents a groundbreaking advancement in the treatment of Alzheimer’s disease, offering new hope to patients in the early stages of this devastating illness.
Patients and healthcare professionals are encouraged to report any adverse effects through the MHRA’s Yellow Card scheme, ensuring ongoing vigilance in monitoring the safety of this newly approved treatment.
