Today, the UK Medicines and Healthcare products Regulatory Agency (MHRA) announced the approval of donanemab for the treatment of mild cognitive impairment or mild dementia due to Alzheimer’s disease (AD). This approval, which comes two months after lecanemab was approved by the UK regulator, was based on data from the Phase 3 TRAILBLAZER-ALZ2 study, which enrolled 1,736 participants with early AD. As well as amyloid plaques, participants had evidence of tau protein accumulation in their brains and were accordingly stratified into two groups (low-medium or high tau).
TRAILBLAZER-ALZ2 demonstrated a 35% slowing of clinical decline for participants with low to medium levels of tau, equating to a 4.4-month delay in disease progression. In the overall population, there was a 22% slowing of clinical decline, as measured on the iADRS scale for cognitive and functional impairment. Similar to other anti-amyloid drugs, donanemab treatment was associated with the development of amyloid-related imaging abnormalities (ARIA), a potentially severe side effect linked to brain microbleeds and swelling. The incidence of ARIA in TRAILBLAZER-ALZ2 was much higher in participants carrying two copies of the ApoE4 gene (40.6%) compared to participants who weren’t ApoE4 carriers (15.7%).
In its press release, the MHRA explained that donanemab meets acceptable standards of safety, quality and efficacy. The regulator stated that people should receive genetic testing to ascertain their ApoE4 status, and that people carrying two copies of ApoE4 should not receive donanemab. The MHRA also ruled out treatment of people who are on anticoagulants, as the risks in this group are considered to be greater than the benefits of receiving donanemab. A controlled access programme was mandated, with obligatory enrolment of patients in a central registration system during treatment. A post-authorisation safety study will also be conducted, particularly focusing on the safety and benefit-risk profile of donanemab in routine clinical practice.
While the marketing of donanemab in the UK has been authorised by the MHRA, the National Health Service (NHS) will not provide coverage for the drug, according to draft guidance issued by the National Institute for Health and Care Excellence (NICE). In a press release published today, NICE explained that donanemab does not currently demonstrate value for the NHS, based on present evidence on clinical benefit and cost-effectiveness of the drug. In particular, they cited uncertainties on how much benefit donanemab provides to patients, how long benefits last after stopping treatment, and the costs of administering donanemab on the NHS. A consultation on the draft guidance will close on 20 November, with the Committee expected to provide a final ruling in early 2025.
Donanemab is currently under review at the European Medicines Agency, with an outcome anticipated during the first quarter of 2025.
Read the MHRA press release: https://www.gov.uk/government/news/donanemab-licensed-for-early-stages-of-alzheimers-disease-in-adult-patients-who-have-one-or-no-copies-of-apolipoprotein-e4-gene
Read the NICE press release: https://www.nice.org.uk/news/articles/new-alzheimer-s-treatment-donanemab-does-not-currently-demonstrate-value-for-the-nhs-says-nice