Approved in 2021 under the accelerated approval pathway, aducanumab’s path has been met with controversy and lack of industry support.
Christopher A. Viehbacher
According to an announcement from Biogen, the company has decided to discontinue the development and commercialization of aducanumab (Aduhelm) 100 mg/mL injection for intravenous use and will terminate its postmarking confirmatory phase 4 ENVISION study. The decision was not based on efficacy or safety concerns, but rather to reallocate funds towards Biogen’s Alzheimer disease (AD) pipeline.1
Aducanumab, an antiamyloid therapy, was approved under the accelerated approval pathway in June 2021 as a treatment for patients with early-stage AD with a confirmed presence of amyloid-ß. In January 2023, Biogen began a strategic review of its research and development efforts, with the intention to gauge external financing and partnership opportunities. After considering the time and investment required for ENVISION, as well as the likely advancements by the time it would be complete, the company decided to change gears.
The company did not identify any potential strategic partners or external financing, and recorded a one-time charge of approximately $60 million related to close out costs for the program in the fourth quarter of 2023. Biogen has also terminated the licensing of aducanumab, which will now revert back to Neurimmune, the company that originally discovered the monoclonal antibody. Furthermore, Biogen will divert its resources to its antisense oligonucleotide targeting tau agent BIIB080 and its small oral molecule inhibitor BIIB113, as well as continue to advance lecenamab (Leqembi; Eisai).
"As a pioneer in Alzheimer’s disease, Biogen is reprioritizing resources to build a leading franchise to address the multiple pathologies of the disease and patient needs. We plan to further advance the launch of LEQEMBI, together with Eisai, and continue to bolster innovation with the development of the other assets in our pipeline,” Christopher A. Viehbacher, president and chief executive officer, Biogen, said in a statement.1 "When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed. ADUHELM was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field."
Biogen submitted its final study protocol for ENVISION to the FDA in March 2022, with a target enrollment of 1500 patients. The 18-month study was intended to confirm the efficacy and safety of aducanumab using change in Clinical Dementia Rating-Sum of Boxes score as the primary end point.2 The trial’s secondary end points included change in amyloid PET and tau PET, as well as scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13), Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory–Mild Cognitive Impairment Version (ADCS-ADL-MCI), Integrated Alzheimer's Disease Rating Scale (iADRS), Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory.
ENVISION was not the first postmarketing study of aducanumab to be terminated. In June 2022, according to an update to National Institutes of Health records, the phase 4 ICARE-AD trial (NCT05097131) was discontinued as "a result of the national policy for coverage." The expectation was that there will be limited aducanumab prescription and usage in routine clinical practice making the study not feasible for enrollment.3
"We have gained significant insight from the development of ADUHELM and will carry this forward as we continue our pioneering work in Alzheimer’s disease,” Priya Singhal, MD, MPH, head of development at Biogen, said in a statement.1 "We’d like to sincerely thank the trial investigators, healthcare providers, advocates, patients and families involved in the development of ADUHELM. We are grateful to Neurimmune for its scientific contributions and collaboration over many years."
Aducanumab was originally approved on 2 phase 3 trials—EMERGE (NCT02484547) and ENGAGE (NCT02477800)—1 of which met its primary end point and 1 that did not. Designed to treat amyloid plaques in patients with AD, the agent was the first in its class of antiamyloid therapies, opening the door for the subsequent approval of lecanemab, which received approval in January 2023. At the time of its approval, aducanumab became the first greenlit agent for AD since 2003.4
