Amid significant controversy, the US Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Aduhelm, Biogen/Eisai) for the treatment of Alzheimer's disease (AD), disregarding the recommendation by its own advisory panel not to approve the drug.
Aducanumab was approved using the accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
However, under this pathway, the FDA requires Biogen to conduct a new randomized, controlled clinical trial to verify the drug's clinical benefit. In an FDA release, the agency said if the drug fails to show clinical benefit in this trial it has the option to withdraw its approval.
Aducanumab's approval marks the first new treatment approved for AD since 2003 and is the first to target beta-amyloid, the hallmark pathology of the disease.
In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.
The FDA noted that today's approval was based on three separate double-blind, randomized, dose-ranging studies representing a total of 3382 patients with AD. Those receiving the active drug, said the FDA, had significant dose- and time-dependent reduction of beta amyloid plaque, while those in the control group had no reduction in amyloid.
AD is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones, said Patrizia Cavazzoni, MD, director of the FDA's Center for Drug Evaluation and Research.
"Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer's," she added.
The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.
As reported by Medscape Medical News, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of an interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.
However, in an about-face 7 months later, Biogen and Eisai announced that a new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.
Although ENGAGE still didn't meet its primary endpoint, data from its new analysis "supported" the EMERGE findings, the drug companies said at the time.
However, 1 year later, a majority of the members of the FDA's advisory panel were against the drug's approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.
As reported by Medscape Medical News, a Viewpoint written by three of the committee members notes that results from the drug's only large positive clinical trial fell short.
"There is no persuasive evidence to support approval of aducanumab at this time," they write.
Groups such as Public Citizen's Health Research Group not only agree with the Viewpoint's authors, they also criticized the FDA for its collaboration with the drug's manufacturers on briefing documents and more.
On April 1, Health Research Group members sent a letter to the US Secretary of Health and Human Services requesting temporary suspension of the FDA's neuroscience chief Bill Dunn, MD, because of his role in supervising the collaboration.
Alzheimer Association Weighs In
The Alzheimer's Association has been a proponent of the drug throughout its development.
Ahead of today's news, the organization noted in a statement that a decision to approve "would be historic" because it would make aducanumab "the first drug to slow Alzheimer's disease" and would mark the beginning of a new future for AD treatments.
"The Alzheimer's Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference" for patients with AD, it said.
Kristen Clifford, chief program officer for the Alzheimer's Association, told Medscape Medical News at the time that approval would be considered a "victory" for patients with AD and for the field overall.
"For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life," Clifford said.
"If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer's and their families," she added.
Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. "This treatment would encourage earlier diagnosis of the disease," she said.
In a new statement released today, the Alzheimer's Association applauded the drug's approval.
"This FDA drug approval ushers in a new era in Alzheimer’s treatment and research, " said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer. "History has shown us that approvals of the first drug in a new category invigorates the field, increases investments in new treatments, and encourages greater innovation. We are hopeful and this is the beginning — both for this drug and for better treatments for Alzheimer's."
Cite this: FDA Approves Controversial Alzheimer's Drug Aducanumab (Aduhelm) - Medscape - Jun 07, 2021.