Real-World Registry Study Shows Alzheimer’s Drug Safety Outcomes

The first interim safety results from a multicenter, safety surveillance study of Alzheimer’s disease patients treated with lecanemab (Leqembi) in real-world clinical practice were consistent with the known safety profile of the drug, researchers said.

No new safety signals were observed in the Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) registry, reported Marwan Sabbagh, MD, of the Barrow Neurological Institute in Phoenix, and co-authors at a poster session at the American Academy of Neurology annual meeting.

“The data produced by clinical trials is not always exactly what is seen in clinical practice because studies are necessarily constrained by factors that enable them to achieve their objectives, such as specific eligibility criteria intended to enable a successful study,” noted co-author Steven Hersch, MD, PhD, vice president of clinical research at Eisai in Boston.

“Study personnel and participants who are motivated to participate in studies can’t be considered fully representative of practicing healthcare professionals and the patients they care for,” Hersch told MedPage Today. “Data from real-world experience add to what is learned in clinical trials and can confirm the important findings that formed the basis of approval while revealing new findings that may be important to understand, such as new safety signals.”

Lecanemab, an antibody directed against aggregated soluble and insoluble forms of amyloid beta, was approved in 2023 to treat early symptomatic Alzheimer’s disease based on the CLARITY-AD trial and other studies. The drug carries a boxed warning that amyloid-related imaging abnormalities with edema (ARIA-E) or ARIA with hemosiderin deposition (ARIA-H) can occur. ARIA is often asymptomatic; in rare cases, it can be fatal.

ALZ-NET was launched in 2022 as the first network developed specifically for new FDA-approved Alzheimer’s treatments, with the goal of collecting real-world evidence about the drugs and their side effects. The ALZ-NET registry is sponsored by the Alzheimer’s Association, and is managed and operated by the American College of Radiology.

Physicians participating in ALZ-NET prescribe lecanemab at their discretion, Sabbagh and colleagues noted. As of May 23, 2025, a total of 742 patients in ALZ-NET had received lecanemab, with a mean treatment duration of 8.4 months. The mean age of this group was 74 years; 55.4% of participants were women and 87.1% were Caucasian.

The incidence of ARIA-E was 5%, and 1.1% of cases were symptomatic. All ARIA-E cases occurred within the first 6 months of treatment. ARIA-H occurred in 7% of participants, including 1.3% who were symptomatic. Most ARIA events — 97.3% of ARIA-E and 96.2% of ARIA-H cases — were mild to moderate in severity.

ARIA-E and ARIA-H each led to treatment discontinuation in 1.6% of participants. Intracerebral hemorrhage larger than 1 cm occurred in two participants (0.3%).

ARIA events were more common in APOE4 gene carriers than noncarriers, the researchers noted. Among carriers, APOE4 homozygotes were associated with higher frequency of ARIA than heterozygotes.

Two deaths were reported: one due to pulmonary embolism, the other to bile duct cancer. The pulmonary embolism death was considered possibly related to lecanemab by the investigators.

“Patients with early Alzheimer’s disease receiving care in real-world clinical practice are very similar to the patients studied in the clinical trials and are encountering adverse events, especially ARIA, that are similar in type, frequency, and severity,” Hersch noted.

“The safety profile of lecanemab observed in the clinical trials is thus continuing in clinical practice as represented by this important real-world safety surveillance study,” he added.

ALZ-NET includes 266 sites and over 3,600 patients treated with anti-amyloid-targeting therapies, according to an update from the Alzheimer’s Association last December. Data from a subset of more than 600 patients who received these drugs for a year showed safety and effectiveness in line with clinical trial results.