On November 6, 2020, the 11-person U.S. Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs Advisory Committee failed to certify the effectiveness of Biogen’s new drug, Aducanumab (BIIB037), as a treatment for Alzheimer’s disease. Voting was based on the results of the EMERGE and ENGAGE Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab. Voting was also based on the results of PRIME, a Phase 1b randomized, multicenter study that included a 12-month, double-blind, placebo-controlled period followed by a dose-blinded long-term extension period.
Results of the voting were as follows:
- On the question, “Does Study 302 (EMERGE), viewed independently and without regard for Study 301 (ENGAGE), provide strong evidence that supports the effectiveness of aducanumab for the treatment of Alzheimer’s disease?”: 1 yes, 8 no and 2 uncertain.
- On the question, “Does Study 103 (PRIME) provide supportive evidence of the effectiveness of aducanumab for the treatment of Alzheimer’s disease?”: 0 yes, 7 no and 4 uncertain.
- On the question, “Has the Applicant presented strong evidence of a pharmacodynamic effect of aducanumab on Alzheimer’s disease pathophysiology?”: 5 yes, 0 no and 6 uncertain.
- On the question, “In light of the understanding provided by the exploratory analyses of Study 301 and Study 302, along with the results of Study 103 and evidence of a pharmacodynamic effect on Alzheimer’s disease pathophysiology, it is reasonable to consider Study 302 as primary evidence of effectiveness of aducanumab for the treatment of Alzheimer’s disease?”: 0 yes, 10 no and 1 uncertain.
FDA Advisory Committees provide non-binding recommendations for consideration by the FDA. With the opinions expressed at the Advisory Committee and the data presented, the FDA will continue the review process with a decision on whether to approve the aducanumab Biologics License Application by March 7, 2021.
Aducanumab (BIIB037) is an investigational human monoclonal antibody studied for the treatment of Alzheimer’s disease. Based on clinical data from people with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease, aducanumab has the potential to impact underlying disease pathophysiology, slow cognitive and functional decline and provide benefits on the individual’s ability to perform activities of daily living, including conducting personal finances, performing household chores, such as cleaning, shopping, doing laundry, and independently traveling out of the home. If approved, aducanumab would be the first treatment to meaningfully change the course of the disease for individuals living with Alzheimer’s disease.
EMERGE and ENGAGE were Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab. The participants had mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease dementia, which was defined as Mini-Mental State Examination (MMSE) scores of 24 to 30. The primary objective of the studies was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in reducing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Secondary objectives were to assess the effect of monthly doses of aducanumab as compared to placebo on clinical decline as measured by the MMSE, Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI).
PRIME was a Phase 1b randomized, multicenter study that included a 12-month, double-blind, placebo-controlled period followed by a dose-blinded long-term extension period. The participants had prodromal Alzheimer’s disease or mild Alzheimer’s disease dementia with MMSE scores of 20-30. The safety and tolerability of aducanumab was the primary aim of the study. Secondary outcomes were: the effect of aducanumab on brain amyloid plaque content as measured by [18F]-florbetapir PET, the pharmacokinetics of aducanumab, and the immunogenicity of aducanumab. Clinical efficacy endpoints were pre-specified in the study protocol as exploratory.
Biogen discovers, develops, and delivers worldwide therapies for people with serious neurological and neurodegenerative diseases, as well as related therapeutic targets. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Biogen currently has a portfolio of medicines to treat multiple sclerosis, has a treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease, dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.
This was reported by Biogen on November 6, 2020.