Updated Aduhelm label restricts agent's use to mild cognitive impairment, dementia

The FDA approved an updated label for Aduhelm that emphasizes the disease stages examined in the clinical trials, specifically stating that the agent should be initiated in patients with mild cognitive impairment or dementia.

The updated label for Aduhelm (aducanumab, Biogen/Eisai), which was announced in a press release issued by Biogen, includes the following statements, according to the press release: “Treatment with Aduhelm should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”

The FDA approved Aduhelm, which is indicated for the treatment of Alzheimer’s disease, last month under an accelerated approval. It became the first new treatment to be approved for AD since 2003 and was also the first to target the “fundamental pathophysiology” of AD, according to the press release issued by the FDA at the time of the approval.

The prescribing information for Aduhelm also 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 issued by the FDA.

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 shortly after Aduhelm was approved. "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 from the FDA.

References:

Biogen. FDA approves updated Aduhelm prescribing information to emphasize population studied in clinical trials. Available at: https://investors.biogen.com/news-releases/news-release-details/fda-approves-updated-aduhelmtm-prescribing-information-emphasize. Accessed July 9, 2021.

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 July 9, 2021.