Aducanumab: What a Difference 1 Year Makes—Not
The peer-reviewed results of the aducanumab phase 1B study in prodromal and mild AD are now available in Nature. And while some media outlets are touting this amyloid-targeting MAb as “revolutionary” on the basis of the newly published article, the 1-year results are absolutely no different than what was reported by the development company, Biogen, 1 year ago. Take a look at the article’s supplementary data tables here and here and compare them with what I tabulated in July of 2015. The values are exactly the same with no changes in statistical differences.
That said, I think we can all agree that the evidence for aducanumab’s ability to reduce brain amyloid is there. However, that benefit—if it is a benefit—is associated with a significant risk of ARIA-E, particularly in APOE ε4 carriers (55% at 10 mg/kg dosage). The risk of ARIA-E leading to drug continuation discontinuation is 35% (still). Perhaps more important, the evidence for cognitive benefits—meaning the CDR-SB and MMSE score changes—is marginal and not reliably dose-dependent.
It therefore remains my impression (for what that’s worth) that aducanumab is bapineuzumab redux.
AD = Alzheimer disease; APOE ε4 = ε4 allele for the apolipoprotein gener; ARIA-E = amyloid-related imaging abnormalities, edema; CDR-SB = Clinical Dementia Rating scale, Sum of Boxes; mAb = monoclonal antibody; MMSE = Mini-Mental State Examination.
A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on Google + and Twitter.
