Phase 4 Study of Aducanumab for Alzheimer Disease Treatment Plans Announced

As required by the Food and Drug Administration (FDA) as part of the accelerated approval of aducanumab-avwa (Aduhelm; Biogen, Cambridge, MA and Eisai, Woodcliff Lake, NJ) for treatment of Alzheimer disease (AD), plans for a phase 4 study have been announced. The protocol for the study is expected to be submitted to the FDA in March 2022 with enrollment planned to begin in May 2022. 

Aducanumab is approved for the treatment of AD in the US, and clinical guidelines recommend use in people with mild cognitive impairment of mild dementia due to AD, consistent with the population studied in phase 3 clinical trials. Aducanumab approval was granted based on data showing that people treated with aducanumab vs placebo had lowered levels of amyloid β, one of the pathologic hallmarks of AD. 

Enrollment in the phase 4 study is expected to be 1,300 participants with early AD with a clinical endpoint at 18 months after initiation of treatment. It is expected that participants will also have the option to continue treatment for up to 48 months. 

“We are delivering on our commitment to accelerate the timelines with the goal to complete the confirmatory study well ahead of schedule,” said Priya Singhal MD, MPH, head of Global Safety & Regulatory Sciences and interim head of Research & Development at Biogen “Together with EMBARK, Biogen’s redosing study, and the ICARE AD study, we aim to provide data from real-world practice and clinical trials to further inform patient and physician decisions about treatment.”

“I am very encouraged by this update and Biogen’s and Eisai’s goal to complete the trial in four years after its initiation, approximately half of the time that the FDA requested as part of the accelerated approval,” said Marwan Sabbagh, MD, FAAN, professor of Neurology, Alzheimer's and Memory Disorders Division, Barrow Neurological Institute. “This is a significant commitment from the companies. It takes time to execute a complex, global trial of this nature, so I am pleased to see the high level of priority being afforded to this study.”

Potential adverse events with aducanumab include amyloid related imaging abnormalities (ARIA), which can cause symptoms of headache, confusion, dizziness, vision changes and nausea. Brain MRI monitoring for ARIA and ARIA with edema (ARIA-E), which can be serious, is required.