HQ Team
August 30, 2025: The U.S. Food and Drug Administration (FDA) is recommending an additional magnetic resonance imaging in Alzheimer’s disease patients receiving Leqembi (lecanemab), an amyloid beta-directed antibody therapy.
This requirement comes after safety concerns were raised regarding a rare but serious side effect known as amyloid-related imaging abnormalities with edema (ARIA-E). This can result in brain swelling or fluid buildup — potentially leading to life-threatening complications such as seizure or even death.
Recently, six fatal cases were identified in patients experiencing severe ARIA-E symptoms soon after their third infusion of the medication.. These findings prompted the agency to revise its prescribing guidelines, now requiring an additional MRI scan prior to the third infusion. The previously recommended timeframe was before the fifth, seventh, or fourteenth infusion.
ARIA-E and Leqembi link
ARIA-E has been linked to Leqembi since its approval in 2023, typically manifesting as asymptomatic changes visible only through MRI. However, the FDA’s recent in-depth analysis uncovered concerning patterns of ARIA-E occurring earlier in the treatment timeline than previously anticipated.
The FDA’s revised monitoring schedule aims to identify ARIA-E at its earliest stages, enabling healthcare providers to act swiftly. Patients diagnosed with ARIA-E may need treatment delays or discontinuation to reduce risks of progression. The FDA emphasizes that early detection is critical, as some ARIA-E cases can escalate rapidly even after initial detection.
For patients and caregivers, this means staying vigilant about symptoms such as headache, confusion, dizziness, vision changes, nausea, or seizures. Anyone experiencing such symptoms should seek immediate medical attention and undergo urgent MRI evaluation. Similarly, healthcare professionals are urged to closely monitor patients for ARIA-E symptoms and adhere to the updated monitoring schedule to ensure timely intervention.
Risks vs benefit
Leqembi, approved in 2023, is designed to slow the progression of Alzheimer’s disease in patients with mild cognitive impairment or mild dementia by removing beta-amyloid plaques from the brain. While it offers hope for slowing disease progression, it carries significant risks, including ARIA-E.
The FDA has said that patients and caregivers should discuss risks with their healthcare providers and to report any adverse effects to the FDA MedWatch program.
Reuters noted that the FDA requires patients on rival Eli Lilly and Co.’s Alzheimer’s drug Kisunla to obtain a brain MRI before the second, third, fourth, and seventh infusions.
On Thursday, Prothena Corporation plc shared results from the Phase 1 ASCENT clinical program in participants with early symptomatic Alzheimer’s disease (AD).
PRX012 was associated with higher overall ARIA-E rates relative to FDA-approved anti-Aβ antibodies, making PRX012 less appropriate for the patients studied in the ASCENT clinical program. Prothena called the ARIA-E profile in early symptomatic Alzheimer’s “non-competitive.”
Global context
The European Medicines Agency (EMA) granted conditional approval for lecanemab, for the treatment of early Alzheimer’s disease in certain patients.This decision follows a previous rejection in July 2024, where the EMA deemed the potential risks associated with the drug outweighed its benefits.
Leqembi’s approval follows similar endorsements from regulatory bodies in other countries. In August 2024, Britain’s Medicines and Healthcare Products Regulatory Agency (MHRA) also approved lecanemab, emphasizing its potential as a treatment option. The drug has been praised by Alzheimer’s researchers and advocacy groups for being one of the first treatments aimed at modifying the disease rather than merely alleviating symptoms.
This update serves as a reminder of the delicate balance between advancing medical breakthroughs and prioritizing patient safety. As treatments for complex diseases like Alzheimer’s continue to evolve, early monitoring and clear communication between patients, caregivers, and healthcare professionals remain essential.
