Papers of the Week

To review the data informing the US Food and Drug Administration (FDA) approval for aducanumab for mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). At the time of writing there were no peer-reviewed published studies on aducanumab. All data presented are derived directly from the material Biogen submitted to the FDA for approval. The three studies that will be reviewed are: Multiple Dose Study of Aducanumab in Participants With Prodromal or Mild AD (PRIME), 221AD302 Phase 3 Study of Aducanumab in Early AD (EMERGE), 221AD301 Phase 3 Study of Aducanumab in Early AD (ENGAGE). PRIME, which was a phase 1 study, demonstrated the most common adverse drug reactions were amyloid-related imaging abnormalities (ARIA), which occurred at rates up to 47% (10 mg/kg group), headache (25%), urinary tract infection (16%), and upper respiratory tract infection (19%). EMERGE demonstrated that high-dose aducanumab was clinically significant at slowing down clinical decline. However, ENGAGE was terminated early based on a futility analysis. Prior to termination ENGAGE demonstrated no clinical difference between treatment and placebo regarding the primary endpoint of slowing clinical decline. Based on the data to date, it is difficult to accurately assess the role of aducanumab in patients with MCI or mild AD. EMERGE showed benefit with high-dose aducanumab slowing clinical decline. However, ENGAGE did not duplicate this benefit. With conflicting evidence of positive outcomes, future phase III studies are needed to confirm efficacy.