Understanding Safety, Amyloid-Related Imaging Abnormalities With Lecanemab: Sharon Cohen, MD, FRCPC

WATCH TIME: 3 minutes

"You can’t go without MRI monitoring, but in skilled hands, it’s generally a safe therapy, with ARIA not being a reason that people have to drop out. Patients who have ARIA are usually asymptomatic and can resume therapy, or either be dosed through if they’re radiographically asymptomatic."

Part of the reason for the continued failures of Alzheimer disease (AD) agents stems from the amyloid-related imaging abnormalities (ARIA) seen as a result from these drugs during clinical trials. Last year’s FDA approval of aducanumab (Aduhelm; Biogen) was met with controversy, as ARIA was observed in 35.2% of the treated patients in the phase 3 EMERGE (NCT02484547) and ENGAGE (NCT02477800) trials, both of which served as part of the drug’s pathway to approval.¹

Lecanemab (Biogen/Eisai), an investigational humanized monoclonal antibody, represents another potential treatment for the AD community, with a PDUFA date scheduled for January 6, 2023. As part of an agreement with the FDA, the companies will provide results from the ongoing phase 3 Clarity AD (NCT03887455) trial as a confirmatory study to verify the benefit of the agent. Recently announced findings from the trial showed that the incidence of ARIA-edema/effusions (ARIA-E) was 12.5% in those treated with lecanemab and 1.7% in those on placebo.²

Furthermore, 2.8% of lecanemab-treated patients had symptomatic ARIA-E vs 0.0% in the placebo group. Eisai plans to present the data at the upcoming Clinical Trials on Alzheimer’s Congress (CTAD), held November 29th to December 2nd. To learn more about the rate of ARIA-E in lecanemab and the significance of the safety findings, NeurologyLive® sat down with Sharon Cohen, MD. Cohen, a neurologist and assistant professor at the University of Toronto, discussed why ARIA should be emphasized as the main side effect of lecanemab, but that overall, therapy is safe, and better than previous agents. She also provided an overview of the upcoming meeting and what clinicians should be aware of, including the data from Clarity AD.

REFERENCES:
1. Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022;79(1):13-21. doi:10.1001/jamaneurol.2021.4161.
2. Lecanemab confirmatory phase 3 clarity ad study met primary endpoint, showing highly statistically significant reduction of clinical decline in large global clinical study of 1,795 participants with early Alzheimer’s disease. News release. Eisai, Biogen. September 27, 2022. Accessed September 29, 2022. https://www.prnewswire.com/news-releases/lecanemab-confirmatory-phase-3-clarity-ad-study-met-primary-endpoint-showing-highly-statistically-significant-reduction-of-clinical-decline-in-large-global-clinical-study-of-1-795-participants-with-early-alzheimers-disease-301634888.html