New Alzheimer’s drugs are raising hopes, but modest benefits, ARIA safety risks, high costs, and regulatory disagreements show how uncertain the path to meaningful treatment remains.
From hope to uncertainty: regulating novel drugs for Alzheimer's disease. Image Credit: ER Pictures / Shutterstock
A recent World Report published in The Lancet examines the evolving therapeutic landscape and regulatory hurdles surrounding Alzheimer’s disease (AD). Regulators debate whether the clinical benefits of new drugs outweigh their safety concerns and whether those benefits can translate into meaningful patient outcomes. This has led to conflicting approval decisions across countries. Scientists are now developing safer drugs that target broader disease mechanisms and testing them in people at high risk for AD before symptoms appear. Such efforts could advance precision medicine and help reduce the global burden of AD.
AD is a brain disease that damages nerve cells and causes millions of dementia cases worldwide. The disease burden is projected to rise from 55 million dementia cases globally in 2020 to 78 million by 2030, increasing the need for better treatments. Although many new drugs are being tested, health agencies often differ in their views on approving new drugs based on clinical outcomes. Agencies such as the United States Food and Drug Administration (US FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK) often differ from the European Medicines Agency (EMA).
In this report, the author Nayanah Siva examined regulatory obstacles and emerging treatments for AD and suggested steps to improve disease outcomes.
Overview of the current regulatory landscape
Different health agencies around the world do not unanimously agree on whether new drugs for AD should be approved. Many recently approved or late-stage disease-modifying drugs target amyloid β accumulation in the Alzheimer’s disease brain, although amyloid’s role as a primary disease driver remains debated. Some officials believe that new drugs offer valuable clinical benefits for AD patients. Other regulators believe their side effects may outweigh their benefits.
For example, donanemab received approval for use in the US and the UK in 2024. However, European regulators initially rejected it because of safety concerns. The EMA later recommended marketing authorization for the drug in a restricted patient population, supported by additional safety data from a modified dosing regimen, for people with one or no apolipoprotein E4 (ApoE4) gene copies. Another drug, lecanemab, received FDA approval in 2023 and MHRA approval in 2024, although European regulators initially rejected it before accepting it later with restrictions. Aducanumab received accelerated FDA approval in 2021 but was rejected in several other regions before being withdrawn in 2024.
Scientists find that these drugs may slow cognitive and functional decline, but they do not cure or reverse AD symptoms. In early investigations, donanemab reduced AD progression by about 35% on the integrated Alzheimer’s Disease Rating Scale over 72 weeks in patients with early symptomatic AD. Although the treatment slowed the decline, some patients developed microbleeds and swelling in the brain, collectively known as amyloid-related imaging abnormalities (ARIAs). In the pivotal trial, ARIA was detected in 36.8% of donanemab-treated patients and 14.9% of placebo-treated patients, with 1.6% of treated patients experiencing serious ARIA events. Lecanemab showed a 27% slowing of decline on a different clinical scale over 18 months, along with ARIA side effects.
Doctors can manage ARIA by prescribing genetic tests, periodic magnetic resonance imaging (MRI) scans, and closely observing patients. Despite this, many scientists question whether removing amyloid actually alters the disease course or merely reduces a biological marker associated with it. The report cites the Nun Study case of Sister Mary, who maintained high cognitive function until death despite extensive amyloid plaques at autopsy, further increasing scientific concerns.
Regulatory approval also does not always translate into patient access. In 2025, the United Kingdom’s National Institute for Health and Care Excellence ruled that donanemab and lecanemab would not be routinely available on the National Health Service because their high costs did not justify their modest clinical benefits, although both drugs later returned for re-evaluation after an appeal involving unpaid carer burden.
Addressing limitations and future directions
Scientists now believe that AD should be detected more proactively to initiate early treatment, ideally before major brain damage and memory changes occur. Clinical trials are testing new drugs in high-risk individuals who do not yet show AD symptoms. They are exploring other possible mechanisms, such as brain inflammation, infections, and metabolic changes, to develop more effective drugs.
Scientists are also looking for safer treatments that are also more convenient for use. For example, early studies suggest that the experimental drug trontinemab can clear amyloid plaques with fewer side effects while entering the brain more effectively. Ongoing efforts are aimed at achieving similar efficacy with subcutaneous injections. If found effective, such injections could be administered at home, considerably reducing hospital visits.
Health agencies and governments must increase investments in trials testing different types of drugs targeting multiple biological processes involved in AD. In fact, the treatment landscape already appears to be shifting. Researchers are now broadening beyond amyloid-centered approaches, with more than 150 new drugs under test targeting different AD-related mechanisms.
Health experts now suggest that scientists must develop treatments using a more patient-centered approach. New drugs should aim to improve the quality of life for AD patients rather than simply altering lab test results. Individuals would be more willing to adopt treatment strategies that help them perform daily tasks or preserve their memory. Health governments and agencies must also conduct transparent, balanced evaluations and clarify outcomes to increase trust.
Based on the report, regulatory bodies often disagree on whether new drugs should be approved, restricted, reassessed, or made routinely available to patients. The overall outlook, nevertheless, appears hopeful. Scientists worldwide increasingly agree that strategies enabling earlier diagnosis, earlier intervention, and targeting multiple biological pathways involved in the disease could ultimately improve patient care in the tnear future
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