The Medicines And Healthcare Products Regulatory Agency Has Today 22 August 2024
22nd August 2024
Lecanemab is the first treatment for Alzheimer's disease licensed for use in Great Britain that shows some evidence of efficacy in slowing progression of the disease.
As for any new medicine, this decision was made with expert scientific advice on the benefit risk of lecanemab from the Commission on Human Medicines (CHM), the government's independent advisory body.
Julian Beach, MHRA Interim Executive Director, Healthcare Quality and Access, said:
Licensing medicines which meet acceptable standards of safety, quality and efficacy is a key priority for us.
We're assured that, together with the conditions of the licence approval, the appropriate regulatory standards for this medicine have been met.
As with all medical products, we will keep its safety under close review, and with a controlled post-authorisation safety study to be undertaken, we will ensure that the benefit risk of lecanemab in clinical use is closely followed up.
Lecanemab is approved to treat adults in the early stages of Alzheimer's disease who have one or no copies of the apolipoprotein E4 gene (ApoE4). A person can have no copies, one copy or two of this gene. Approximately 15% of those diagnosed with Alzheimer’s have two copies of this gene, known as homozygous patients, and are at increased risk of developing Alzheimer’s disease, while people with one copy also have an increased risk.
In the main clinical trial of 1,795 people with early Alzheimer’s disease, including patients with mild cognitive impairment or mild dementia and confirmed presence of amyloid beta pathology, ApoE4 homozygous patients who received lecanemab were at higher risk of developing Amyloid Related Imaging Abnormalities (ARIAs), which are most commonly seen as temporary swelling in one or more areas of the brain (ARIA-E) or small spots of bleeding in or on the surface of the brain (ARIA-H).
Whilst most ARIA events were only seen on a brain scan and did not cause any symptoms, in a small number of patients serious symptoms occurred. The risk of symptomatic, serious radiographic imaging and recurrent ARIA events were higher in ApoE4 homozygous patients compared with those with one or no copies of the gene. This increased risk was 45% in the homozygous group, 19% in the heterozygous group and 13% in the non-carriers, compared to 22%, 9% and 4% respectively in the placebo group.
In addition, the level of benefit in the ApoE4 homozygous patients with 2 copies of the ApoE4 gene, was uncertain compared with ApoE4 heterozygotes, those who have one copy of the ApoE4 gene or non-carriers.
The CHM therefore advised that the risk benefit of lecanemab was favourable in the patients who were ApoE4 non-carriers or heterozygous but not in the homozygous group, and that testing for the APOE4 gene should be carried out before treatment.
Use of lecanemab in patients who are on anticoagulants (blood thinners, including warfarin) or have been diagnosed with cerebral amyloid angiopathy (CAA) on MRI before starting treatment is contraindicated as the risks in these patients are considered to outweigh the benefits.
Lecanemab is a monoclonal antibody which binds to a protein called amyloid beta In Alzheimer’s disease, clumps of amyloid beta protein form plaques in the brain. Lecanemab works by binding to these clumps and reducing them, therefore slowing the progression of the disease.
Lecanemab treatment, a 10mg/kg dose, is administered intravenously in a healthcare setting every two weeks, with each infusion lasting approximately one hour, and it is given to the patient under the supervision of a healthcare professional. If well tolerated, treatment continues until a patient progresses beyond mild Alzheimer’s disease to moderate disease.
Patients in the clinical trial were given either lecanemab (at a dose of 10 mg/kg, once every two weeks) or placebo. At 18 months lecanemab demonstrated a statistically significant reduction in clinical decline when compared with the placebo. A statistically significant reduction in amyloid beta plaque levels in the brain for lecanemab, compared to placebo, was also seen.
The most common side effects of the medicine are infusion-related reactions (which can cause fever and flu-like symptoms), headaches and ARIA.
As with any medicine, the MHRA will keep the safety and effectiveness of lecanemab under close review. To promote safe and effective use and keep the safety and efficacy of lecanemab under close review, initiation of treatment in any patients will be through a central registration system implemented as part of a controlled access programme.
A controlled post-authorisation safety study will be conducted to investigate the safety and benefit-risk profile of lecanemab in routine clinical practice, particularly in relation to incidence and severity of ARIAs and intracerebral haemorrhage, and long-term safety.
Anyone who suspects they are having a side effect from this medicine is encouraged to talk to their doctor, pharmacist or nurse and report it directly to the Yellow Card scheme, either through the website (https://yellowcard.mhra.gov.uk/) or by searching the Google Play or Apple App stores for MHRA Yellow Card.
The authorisation for lecanemab was granted on 22 August 2024 to Eisai.
More information can be found in the Summary of Product Characteristics and Patient Information leaflets which will be published on the MHRA Products website - https://products.mhra.gov.uk/
The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe. All our work is underpinned by robust and fact-based judgements to ensure that the benefits justify any risks.
