Aducanumab Label Revised: Initiate Treatment for Mild Cognitive Impairment or Mild Dementia of Alzheimer Disease

In consultation with the Food and Drug Administration (FDA), prescribing physicians, dementia experts, and patient advocates, Biogen has requested, and the FDA has approved, a label update for the recently approved Alzheimer disease (AD) treatment aducanumab (Aduhelm; Biogen, Cambridge, MA). The label update now includes a statement that 

"treatment 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."

Approval by the FDA on June 7, 2021 was based on reduction of the biomarker amyloid β (Aβ) plaques in the brain, which occurred with aducanumab treatment in all clinical trials. This decision was controversial, however, because improvements in cognition were statistically significant in only 1 of the 3 clinical trials. Even among those who supported approval, the broad indication on the label for "treatment of Alzheimer disease," was met with surprise from many experts that the indication had not matched the participant inclusion criteria in the trials.  

Alfred Sandrock, Jr., MD, PhD, head of Research and Development at Biogen, said, “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 3 Aduhelm clinical trials that supported approval. We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option.”

Aducanumab is the first disease-modifying treatment approved for AD and the first to target Aβ plaque formation, which is among the earliest causative steps in the pathophysiology of AD. However, because symptoms of AD do not occur until decades after Aβ plaques begin to form, evidence of long-term benefits on cognition may not be seen until years after Aβ pathology is treated. This time course also suggests treatment directed at Aβ may be ineffective unless it is begun early in the disease course. 

Real-world use of aducanumab in people with MCI or mild dementia of AD will allow for long-term study that can further test these hypotheses. If proven correct, there will be long-term health benefits on a global scale, and if not, the amyloid hypothesis may be put to rest. Other therapies targeting both amyloid and nonamyloid pathologies seen in AD are in late-stage development and will also aid the quest to reduce the impacts of this devastating disease.