A new Phase 3 clinical trial, called EMBARK, will evaluate the long-term safety and efficacy of aducanumab (BIIB037), an investigational therapy for Alzheimer’s disease in patients who took part in its previous clinical studies.
The trial’s design was described by Carmen Castrillo-Viguera, a medical director at Biogen, in the poster “EMBARK: A Phase 3b, Open-Label, Single-Arm, Safety Study to Evaluate the Long-Term Safety and Efficacy of Aducanumab in Eligible Participants With Alzheimer’s Disease.” The poster was presented at the 2021 American Academy of Neurology annual meeting (AANAM), that ran April 17–22.
Aducanumab, being co-developed by Biogen and Eisai, is an investigational Alzheimer’s treatment currently under review for approval in the U.S., Europe, and Japan. The therapy is designed to remove toxic clumps of proteins found in the brains of Alzheimer’s patients, which are believed to drive the disease.
Development of aducanumab was terminated in 2019, after an independent advisory committee analyzed data from these studies and determined that the investigational medication was unlikely to provide a meaningful benefit.
However, a later analysis that included more data indicated that EMERGE had, in fact, achieved its main goal of improving cognition and function, including memory, orientation, language, and daily living activities, relative to a placebo.
“Based on a larger dataset after the trials were terminated, it was determined that the assumptions in the [prior analysis] were not valid. After databases were logged and analyzed per the pre-specified analysis plan, one of the studies, EMERGE, met the pre-specified primary and secondary endpoints,” Castrillo-Viguera said.
Castrillo-Viguera added that, although ENGAGE did not meet efficacy endpoints, an analysis of findings in a subset of trial participants who had been given a high dose of aducanumab supported the positive findings in EMERGE.
“These results urged Biogen to restart the aducanumab clinical development program, and redosing participants from the previously halted studies became one of our main priorities,” Castrillo-Viguera said.
Biogen initiated EMBARK (NCT04241068) as an open-label clinical trial in patients who were active participants in EMERGE, ENGAGE, or other clinical studies of aducanumab when they were discontinued.
Those who enroll in EMBARK will be treated with aducanumab, regardless of whether they were assigned to the active medication or a placebo in prior trials. The treatment, at a dose 10 mg/kg, is administered by infusion directly into the bloodstream every four months.
Patients will be treated for a total of 24 months (two years), and will be assessed for safety-related outcomes, as well as various clinical measures of the medication’s effect on the body. There is an eight-week screening period before beginning treatment, and an 18-week follow-up period to check safety outcomes after treatment ends.
EMBARK was “really designed to assess two fundamental questions,” Castrillo-Viguera said. “One is, what is the long-term safety and efficacy of aducanumab dosing with the highest dose tested in the Phase 3 trials? And two, what are the changes in clinical and biomarker measures during the treatment gap?”
The trial is expected to enroll by invitation about 1,800 participants at over 300 sites in 20 countries — which, Castrillo-Viguera said, would make it one of the largest ever clinical trials conducted in Alzheimer’s disease.