Updated Plan for a Postmarketing Placebo-Controlled Trial of Aducanumab Announced

Additional information has been released regarding plans for a phase 4 placebo-controlled trial of aducanumab-avwa (Aduhelm; Biogen, Cambridge, MA and Eisai, Woodcliff Lake, NJ) for treatment of early Alzheimer disease (AD). Real-world trials of aducanumab were mandated by the Food and Drug Administration when aducanumab was approved for treatment of AD via the accelerated approval pathway. 

The announcement today regarding the phase 4 confirmatory ENVISION study, of aducanumab in early AD included an increased enrollment target, primary outcome measure, and goals for diversity of enrollment. The primary outcome measure will be change in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) score after at 18 months of treatment with aducanumab vs placebo. The ENVISION study has not yet been submitted to the FDA for approval. 

The target enrollment has been increased from 1,300 to 1,500 with early AD and confirmed amyloid β on neuroimaging. An enrollment goal of having 18% of the study population be Black and Hispanic/Latinx individuals has been set. Although 18% reflects less than half of the 40% of the US population comprised by Black and Hispanic/Latinx people, it is a threefold increase from what is typically seen in AD trial participant populations. The announcement states that Biogen will implement multiple strategies to help overcome barriers to diverse patient enrollment in AD trials (eg, lack of access to medical centers, familiarity with benefit/risk profile of treatment, and financial or logistical burdens).

“It’s important to see this ambitious focus on diversity being prioritized in enrollment and integrated as a key part of the ENVISION clinical trial, so that we can have data from patients who more closely represent what we see in the clinic,” said Dylan Wint, M.D., Cleveland Clinic Lou Ruvo Center for Brain Health, Nevada.