FDA approves Aduhelm, first new Alzheimer's disease treatment since 2003
The FDA today granted accelerated approval for Aduhelm, the first new treatment to be approved for Alzheimer’s disease since 2003.
The drug is also the first to target the “fundamental pathophysiology” of AD, according to the press release issued by the FDA.
“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 [AD],” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the release. “As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
Researchers examined the efficacy of Aduhelm (aducanumab, Biogen/Eisai) in three separate studies that included a total of 3,482 patients. The double-blind, randomized, placebo-controlled, dose-ranging studies in patients with AD demonstrated that patients who received Aduhelm had significant decreases in amyloid beta plaque in both time and dose dependent manners, according to the press release. Patients in the control arm showed no such decreases in amyloid beta plaque, which was quantified with PET imaging.
The prescribing information for Aduhelm includes a warning about amyloid-related imaging abnormalities (ARIA), which most frequently develop as temporary swelling in areas of the brain. While ARIA typically resolves with time and does not induce clinical symptoms, some patients have reported headache, confusion, dizziness, vision changes or nausea, according to the press release.
The prescribing information includes another warning about hypersensitivity reactions, including angioedema and urticaria. The most common side effects associated with Aduhelm involved ARIA, headache, fall, diarrhea and confusion/delirium/altered mental status/disorientation.
Late last year, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee met to discuss a Biologics License Application for Aduhelm. The advisory committee decided not to recommend approval for the agent at the time; concerns centered on the two clinical trials of Aduhelm and issues related to safety, particularly the incidence of ARIA, as well as efficacy.
"The advisory committee had concerns about efficacy and safety," G. Caleb Alexander, MD, MS, professor of epidemiology and medicine at Johns Hopkins Bloomberg School of Public Health, founding codirector of the Center for Drug Safety and Effectiveness and principal investigator of the Johns Hopkins-FDA Center of Excellence in Regulatory Science and Innovation, told Healio Neurology. "In fact, most of the coverage of the advisory committee at the time had to do with the fact that the committee felt the evidence was not persuasive."
Under the accelerated approval, the FDA is requiring Biogen to perform a new randomized controlled trial to verify the drug’s clinical benefit. If that new trial fails to verify clinical benefit, the FDA “may initiate proceedings to withdraw approval of the drug,” according to the press release.
In a statement, the Alzheimer’s Association “enthusiastically [welcomed]” the FDA approval of Aduhelm.
“This FDA drug approval ushers in a new era in Alzheimer’s treatment and research,” Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, said in the statement. “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 [AD].”
Editor's Note: This story was updated on June 8, 2021, to include comments from G. Caleb Alexander, MD, MS.
FDA. FDA grants accelerated approval for Alzheimer’s drug. Available at: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug. Accessed June 7, 2021.