New Alzheimer’s drugs have shown promise, but are not very effective, and ARIA’s safety risks, high costs, and regulatory disagreements demonstrate how uncertain the path to meaningful treatment remains.
From hope to uncertainty: Regulation of novel treatments for Alzheimer’s disease. Image credit: ER Pictures / Shutterstock
Recently published world reports lancet Explore the evolving therapeutic landscape and regulatory hurdles surrounding Alzheimer’s disease (AD). Regulatory agencies are debating whether the clinical benefits of new drugs outweigh safety concerns and whether those benefits translate into meaningful patient outcomes. This has resulted in inconsistent approval decisions from country to country. Scientists are now developing safer drugs that target broader disease mechanisms and testing them in people at high risk of developing Alzheimer’s before symptoms appear. Such efforts could help advance precision medicine and reduce the global burden of Alzheimer’s disease.
Alzheimer’s disease is a brain disease that damages nerve cells and causes millions of people with dementia around the world. The number of people with dementia worldwide is expected to increase from 55 million in 2020 to 78 million by 2030, increasing the need for better treatments. Many new drugs are being tested, and health authorities often have differing views on approving new drugs based on clinical results. Agencies such as the United States Food and Drug Administration (US FDA) and the United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) are often different from the European Medicines Agency (EMA).
In this report, author Nayana Siva examines regulatory obstacles and new treatments for Alzheimer’s disease, and suggests steps to improve disease outcomes.
Overview of the current regulatory situation
Various health organizations around the world do not unanimously agree on whether new drugs for Alzheimer’s disease should be approved. Although many recently approved therapeutics and late-stage disease-modifying drugs target amyloid-β accumulation in the Alzheimer’s disease brain, the role of amyloid as a major disease driver remains controversial. Some officials believe the new drug could provide valuable clinical benefits for Alzheimer’s patients. Other regulators believe the side effects may outweigh the benefits.
For example, donanemab received approval for use in the US and UK in 2024. However, European regulators initially rejected it, citing safety concerns. The EMA later recommended marketing authorization for the drug in a limited patient population, supported by additional safety data from a revised dosing regimen, for people with one or no copies of the apolipoprotein E4 (ApoE4) gene. Another drug, lecanemab, received FDA approval in 2023 and MHRA approval in 2024, but European regulators initially rejected it and later approved it with restrictions. Aducanumab received accelerated FDA approval in 2021, but was rejected in several other regions and withdrawn in 2024.
Scientists have found that while these drugs may slow cognitive and functional decline, they cannot cure or reverse Alzheimer’s symptoms. In early studies, donanemab reduced AD progression by approximately 35% on the Unified Alzheimer’s Disease Rating Scale over 72 weeks in patients with early symptomatic AD. Although treatment has slowed the decline, some patients develop microbleeds and swelling in the brain, collectively known as amyloid-associated imaging abnormalities (ARIA). In this pivotal trial, ARIA was detected in 36.8% of patients treated with donanemab and 14.9% of patients treated with placebo, and 1.6% of treated patients experienced a serious ARIA event. Lecanemab showed a 27% slower decline on various clinical scales over 18 months, along with ARIA side effects.
Doctors can manage ARIA by prescribing genetic testing, regular magnetic resonance imaging (MRI) scans, and monitoring patients closely. Nevertheless, many scientists question whether removing amyloid actually changes the course of the disease or simply reduces biological markers associated with amyloid. The report further raises scientific concerns by citing the case of Sister Mary’s study of nuns who maintained high cognitive function until death despite having extensive amyloid plaques at autopsy.
Additionally, regulatory approval does not always translate to patient access. In 2025, the UK’s National Institute for Health and Care Excellence ruled that donanemab and recanemab were not routinely available in the National Health Service because their high costs were outweighed by their modest clinical efficacy, but both drugs were later brought back for reassessment following an appeal over unpaid carer costs.
Addressing limitations and future directions
Scientists now believe that Alzheimer’s disease needs to be detected more aggressively in order to begin early treatment, ideally before significant brain damage or memory changes occur. Clinical trials test new drugs in high-risk people who are not yet showing symptoms of Alzheimer’s disease. They are studying other possible mechanisms, including brain inflammation, infection, and metabolic changes, to develop more effective drugs.
Scientists are also looking for treatments that are safer and easier to use. For example, early research suggests that the experimental drug trontinnemab can clear amyloid plaques while entering the brain more effectively and with fewer side effects. There are ongoing efforts aimed at achieving similar effects with subcutaneous injections. If effective, such injections could be given at home, potentially significantly reducing hospital visits.
Health organizations and governments need to increase investment in clinical trials testing different types of drugs that target multiple biological processes involved in Alzheimer’s disease. In fact, the therapeutic landscape already appears to be changing. Researchers are currently expanding their work beyond amyloid-centric approaches, with more than 150 new drugs in testing targeting various Alzheimer’s disease-related mechanisms.
Medical experts now suggest that scientists need to use a more patient-centered approach to develop treatments. New drugs should aim to improve the quality of life of Alzheimer’s patients, rather than simply changing laboratory test results. Individuals will be more willing to adopt treatment strategies that help them perform daily tasks and preserve memory. Health governments and health organizations also need to conduct transparent, balanced evaluations and clarify outcomes to improve trust.
Based on these reports, regulatory agencies often disagree about whether a new drug should be approved, restricted, reevaluated, or made routinely available to patients. Nevertheless, the overall outlook looks hopeful. Scientists around the world are increasingly agreeing that strategies that enable earlier diagnosis, earlier intervention, and target multiple biological pathways involved in disease may ultimately improve patient care in the near future.
