The newly updated label language emphasizes the Alzheimer disease stages in which aducanumab was studied, with no additional changes made to its approval pathway.
The FDA announced today that it has approved an updated label for aducanumab (Aduhelm; Biogen) injection 100 mg/mL solution which includes an addition to the Indications and Usage section of the label.1
The updated language states that treatment with aducanumab should be initiated in patients with mild cognitive impairment or mild dementia stages of the disease, the population in which the treatment was initiated in clinical trials. It continues to state that there are no safety or efficacy data on initiating treatment at earlier or later stages of the disease than were studied.
Aducanumab’s indication under the accelerated approval pathway remains the same and continued approval for this indication is still contingent upon verification of clinical benefit in confirmatory trials. There were no additional changes made to the label, including the Important Safety Information section.
“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, head of research and development, Biogen, said in a statement. “We are committed to continue to listen to the community’s needs as clinical practice adapts to this information, first-in-class treatment option.”
Aducanumab became the first FDA-approved disease-modifying agent for the treatment of Alzheimer disease (AD) on June 7, 2021, marking it as the first novel approval for the neurodegenerative condition since 2003.2
The treatment’s pathway to approval was tumultuous and controversial at times. Biogen first announced in March 2019 that it was discontinuing the 2 phase 3 clinical trials evaluating the anti-amyloid agent—EMERGE (NCT02484547) and ENGAGE (NCT02477800), as well as a phase 2 safety study, EVOLVE (NCT03639987)—which was followed by an October 2019 announcement that the company had reversed course on its decision. Later that year at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) annual meeting, December 4–7, 2019 in San Diego, California, new data from EMERGE and a post hoc analysis of a subset of patients who received high-dose treatment in ENGAGE were presented, suggesting that there were statistically significant changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores, with P values of .010 or .031 based on cutoff dates. At that point, Biogen declared its intention to submit the agent to the FDA for review. It its decision to approve, the FDA noted that the late-stage development program consisted of 2 trials, 1 which met its primary end point and 1 that did not. Despite this, they felt as though the data suggested aducanumab “consistently and very convincingly” reduced amyloid plaques in both a dose- and time-dependent fashion. They also noted that it anticipates that this reduction will result in a reduction in clinical decline.
The approval has been met with mixed reactions from the clinical and patient/caregiver communities. A recently published report from the Institute for Clinical and Economic Review (ICER) suggested that Biogen must drastically reduce the price of aducanumab in order for the therapy to be considered cost-effective for patients.3 When calculating the price based on assumed “optimistic” treatment benefits–relying only on the results of the positive study–ICER would price the agent between $11,100 and $23,100 for it to be considered cost-effective, significantly less than the current price, which stands at $56,000 annually.
One of the sticking points has been confusion over which patients are eligible—and would possibly benefit—from treatment. Experts Richard Isaacson, MD, and Marc E. Agronin, MD, recently sat down with NeurologyLive in a Peers and Perspectives series to address questions surrounding aducanumab’s approval and its impact on the Alzheimer community. In the video below, they detail the challenges in identifying the appropriate patient—early in the disease course—for treatment with aducanumab.