Introduction

The therapeutic landscape for Alzheimer’s treatments is presently facing significant attention. Recently, the UK’s National Institute for Health and Care Excellence (NICE) evaluated lecanemab, a drug aimed at slowing cognitive decline in early Alzheimer’s patients. While NICE acknowledged its potential, the high costs and limited benefits led to its non-recommendation for National Health Service (NHS) use. However, other than lecanemab there are three other promising drugs for the treatment of Alzheimers—donanemab, remternetug, and blarcamesine. As part of Ageing Healthy month, we highlight the mechanisms, clinical trial outcomes, and future prospects of these potential treatment options.

Lecanemab: NICE’s Verdict

Lecanemab, also known as Leqembi, targets amyloid plaques in the brain, slowing disease progression by four to six months. Licensed by the Medicines and Healthcare products Regulatory Agency (MHRA), it requires fortnightly infusions and intensive monitoring. Despite its potential, NICE’s independent committee found the benefits too small to justify the cost. Approximately 70,000 adults in England would have been eligible for treatment, but NICE prioritises cost-effective use of NHS resources. The public consultation on this draft guidance will close on 20 September 2024.

Donanemab: A New Hope in Immunotherapy

Developed by Eli Lilly, donanemab is an immunotherapy drug targeting amyloid plaques. Administered intravenously, it showed promising results in the TRAILBLAZER-ALZ2 trial. Involving 1,182 participants, the trial demonstrated a 20-60% reduction in cognitive decline, depending on the severity of brain changes. Furthermore, daily activity decline was reduced by 40%. Following the Food and Drug Administration (FDA) approval in July 2024, the MHRA is expected to review donanemab, focusing on its safety, efficacy, and cost-effectiveness.

Remternetug: The Next Generation

Also from Eli Lilly, remternetug is a second-generation immunotherapy drug. It targets amyloid plaques more effectively and can be administered intravenously or via subcutaneous injections. Initial trials showed significant amyloid plaque clearance within six months, outperforming donanemab. However, some participants experienced brain swelling or bleeding. The ongoing TRAILRUNNER-ALZ1 phase 3 trial aims to further evaluate its safety and efficacy, with results expected by 2025.

Blarcamesine: A Novel Approach

Developed by Anavex Life Science Corp., blarcamesine activates the sigma-1 receptor, preventing protein misfolding implicated in Alzheimer’s. Taken orally as a daily capsule, it also supports mitochondrial function, offering broader neuroprotective effects. At the Alzheimer’s Association International Conference in August 2024, Anavex reported that blarcamesine slowed cognitive decline by over 25%, though it did not significantly impact daily functioning. Mild to moderate side effects, including dizziness and confusion, were observed. Anavex plans to seek marketing approval in Europe by the end of 2024.

Conclusion: Alzheimer’s Treatments

While lecanemab represents a step forward in Alzheimer’s treatment, NICE’s decision highlights the crucial balance between clinical benefits and cost-effectiveness. The drug’s modest impact on cognitive decline, combined with its high cost, underscores the importance of rigorous economic evaluations in healthcare. For the policymakers, these findings stress the need for treatments that offer substantial benefits at sustainable costs. Emerging therapies like donanemab, remternetug, and blarcamesine show promise, but their ultimate value will depend on both clinical efficacy and economic viability. Continued investment and research are essential to develop treatments that are not only effective but also accessible and affordable, ensuring optimal use of healthcare resources.