Researchers call for a strengthened pharmacovigilance approach to monitor the safety and effectiveness of new Alzheimer’s Disease drug

Researchers from the Drug Safety Research Unit are calling for the robust monitoring of the safety of lecanemab, a promising new drug to treat Alzheimer’s Disease (AD).

In a review article, published in the British Journal for Clinical Pharmacology, the researchers discuss the need for ongoing assessment of the safety and effectiveness of lecanemab in the real-world clinical setting in the UK and beyond.

Lecanemab is a novel anti-amyloid monoclonal antibody (mAb) drug, which has shown promise in slowing down early-stage AD. In 2024, the drug was approved for use in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA), followed by an approval by the European Medicines Agency (EMA) in November 2024. However, the National Institute for Health and Care Excellence (NICE) in the UK has not recommended lecanemab for routine NHS use, citing uncertainty regarding the long-term effectiveness of lecanemab and a requirement for more evidence regarding its cost-effectiveness.

In the paper, researchers from the DSRU highlighted the benefits of lecanemab when used for mild cognitive impairment and mild dementia due to AD. Lecanemab has shown a high selectivity for soluble aggregated species of amyloid beta (Aβ),a reduction in mean amyloid burden in early AD, and a reduction in dementia severity and progression compared to placebo. However, as echoed by NICE, they argue that more work needs to be done to establish whether these benefits are clinically meaningful to patients in the long term.

“Any measure of clinical meaningfulness derived from the analysis of efficacy in RCTs may not necessarily be translatable to that observed in the real-world; thus there is a clear need to monitor effectiveness data in real-world clinical settings, particularly over a longer term duration of treatment beyond 18 months,” they write.

In addition, they stress the need for more data to understand any risks associated with the drug as these should be continuously re-evaluated in terms of the benefits observed in clinical practice. Lecanemab has been linked to a higher risk of Amyloid-Related Imaging Abnormalities (ARIA) in clinical trials, which may cause brain swelling and bleeding. These adverse events occurred particularly among patients carrying two copies of the ApoE ε4 gene. Although use has been restricted to patients with one or no copies of the ApoE ε4 gene, clinical vigilance is still advised for all patients during the first 14 weeks of treatment.

They call for a strengthened pharmacovigilance approach for the use of lecanemab in a larger and more diverse population due to the inherent limitations of clinical trials when detecting safety outcomes, the need to minimise the risks in clinical practice, and in light of the differing opinions of regulators and health bodies regarding the use of the drug.

The researchers say: “The post-authorisation monitoring of the complex benefit-risk profile of lecanemab in real-world clinical use should encompass a broad range of pharmacovigilance activities. Post-marketing surveillance of safety and effectiveness should inform a robust, ongoing review and assessment of the benefit-risk profile of lecanemab using a variety of available real-world data (RWD) sources, with an understanding of the strengths and limitations of each data source.”

A proactive review of spontaneous reports of Adverse Drug Reactions (ADRs), including Individual Case Safety Reports (ICSRs), may provide an initial indicator of the reporting of adverse events with the drug in clinical practice. However, spontaneous reporting should be strengthened with RWD from a variety of other sources, including that generated by Post-Authorisation Safety Studies (PASS), the review suggests.

Amy Bobbins, lead author of the paper and Senior Research Pharmacist at the DSRU, commented: “The development of anti-amyloid mAbs, such as lecanemab, represents a significant step forward in AD research. As similar drugs are in various stages of drug development, understanding the benefits and risks of these novel drugs in the real-world setting is essential to support their safe and effective use.

“As more RWD begins to emerge for lecanemab across various clinical settings, the ongoing assessment of safety evidence is crucial to protect the health of patients with AD.”