“Overall, the study demonstrated clearly that this is an effective treatment,” said acting chair Robert C. Alexander, MD, chief scientific officer, Alzheimer’s Prevention Initiative, Banner Alzheimer’s Institute, and research professor, department of psychiatry, University of Arizona, Phoenix, during the meeting.
An intravenous infusion targeting amyloid-beta, lecanemab received accelerated FDA approved earlier in 2023 for the treatment of early Alzheimer’s disease (AD). The company was required to complete a confirmatory study to verify and describe the product’s clinical benefit.
The Peripheral and Central Nervous System Drugs Advisory Committee met to discuss this phase 3 study (CLARITY-AD). The multicenter, double-blind study included 1,795 patients (mean age, 71 years) who had mild cognitive impairment caused by AD or mild AD dementia.
Delayed progression
Study participants had a broad range of comorbidities, and many were concomitantly receiving other medications. Black people were underrepresented in the study at just 3% of the total cohort.
Patients were randomly assigned to receive placebo or lecanemab 10 mg/kg biweekly. In addition to a placebo-controlled period and safety follow-up, the study has an ongoing extension phase of up to 4 years.
The study met its primary endpoint, showing a highly statistically significant 27% less decline on the Clinical Dementia Rating-Sum of Boxes at 18 months (difference in adjusted mean, –0.45; 95% CI, –0.67 to –0.23; P = .00005).
This was supported by a significant 26% difference on the AD Assessment Scale–Cognitive Subscale with 14 tasks (ADAS-Cog 14).
The drug also affected function, with a 37% decrease, compared with placebo, on the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment.
Committee members heard that the results signal delays in disease progression by about 5 months, giving patients more time to live independently and participate in hobbies and interests.
Patients who received the active drug also experienced quality of life benefits. Compared with patients who received placebo, those who took lecanemab had 49% less decline as measured with the European Quality of Life–5 Dimensions scale and 56% less decline as measured by the Quality of Life in AD scale, and caregivers reported less burden.
Lecanemab also affected biomarkers of amyloid, tau, and neurodegeneration, providing a biological basis for the treatment effects consistent with slowing of disease progression.
Unanimous support
All six committee members agreed by vote that the study provides evidence of clinical benefit. They variously descried the study and results as “robust,” “compelling,” “well conducted,” “clear and consistent,” and “clinically meaningful.”
In the active treatment group, there was a higher incidence of amyloid-related imaging abnormalities (ARIAs), which can be serious and life-threatening but are usually asymptomatic. In this study, most ARIAs had resolved by 3 months.
Deaths occurred in 0.8% of the placebo and 0.7% of the treatment group. Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., noted that the numbers of deaths and serious adverse events were “quite similar” in the two groups.
“And for serious ARIA, there was an imbalance favoring placebo, but overall, these were pretty rare,” he said.