On Jun. 7, 2021, Biogen and Eisai announced that the U.S. Food and Drug Administration (FDA) had granted accelerated approval for ADUHELM (aducanumab-avwa) as the first and only Alzheimer’s disease treatment to address a defining pathology of the disease by reducing amyloid beta plaques in the brain.

The accelerated approval has been granted based on data from clinical trials demonstrating the effect of ADUHELM on reducing amyloid beta plaques, a biomarker that is reasonably likely to predict clinical benefit, in this case a reduction in clinical decline. Continued approval for ADUHELM’s indication as a treatment for Alzheimer’s disease may be contingent upon verification of clinical benefit in confirmatory trial(s).

The efficacy of ADUHELM was evaluated in two Phase 3 clinical trials—EMERGE (Study 1) and ENGAGE (Study 2)—in patients with early stages of Alzheimer’s disease (mild cognitive impairment and mild dementia) with confirmed presence of amyloid pathology.

The ADUHELM safety profile is well characterized in over 3,000 patients who received at least one dose of ADUHELM. The most frequently reported adverse event was radiographic detection of events termed Amyloid Related Imaging Abnormalities, or “ARIA.” ARIA (-E and/or -H) was observed in 41 percent of patients treated with ADUHELM 10 mg/kg compared to 10 percent of patients on placebo. Clinical symptoms were present in 24 percent of patients treated with ADUHELM 10 mg/kg who had an observation of ARIA (-E and/or -H), compared to 5 percent of patients on placebo.

The most common symptom in patients with ARIA was headache. Other symptoms associated with ARIA included confusion, dizziness, visual disturbances, and nausea. Adverse reactions that were reported in at least 2 percent of patients treated with ADUHELM and at least 2 percent more frequently than in patients on placebo were ARIA-E, headache, ARIA-H microhemorrhage, ARIA-H superficial siderosis, fall, diarrhea, and confusion/delirium/altered mental status/disorientation.

The effects of ADUHELM were also assessed in the double-blind, randomized, placebo-controlled, dose-ranging Phase 1b study, PRIME (Study 3). In these studies, ADUHELM consistently showed a dose- and time-dependent effect on the lowering of amyloid beta plaques (by 59 percent [p<0.0001] in ENGAGE, 71 percent [p<0.0001] in EMERGE, and 61 percent [p<0.0001] in PRIME).

As part of the accelerated approval, Biogen planned to conduct a controlled trial to verify the clinical benefit of ADUHELM in patients with Alzheimer’s disease.