Updated Results for Biogen’s Aducanumab not Overwhelmingly Positive
In conjunction with a presentation at the ongoing AAIC, Biogen provided a press release of its updated phase 1B data for its anti-amyloid mAb aducanumab in patients with mild AD. As you may recall, Biogen was attempting to thread the needle, so to speak, by investigating an intermediate (6 mg/kg) dosage of the compound. The idea was to preserve whatever clinical and/or amyloid-reducing benefits the drug might offer, while moderating the risk of ARIA-E (ie, drug-related vasogenic brain edema).
The updated results, unfortunately, aren’t terribly impressive and the accompanying buzz is nowhere near that of when the preliminary results were reported in March. Patients receiving aducanumab 6 mg/kg actually fared worse on the MMSE than patients who received the lower dosage (3 mg/kg). Likewise, any changes in the global function score (CDR-SB) with the 6-mg/kg dosage were not statistically significant (vs placebo).
In a more expected fashion, however, the 6-mg/kg dosage significantly reduced the brain amyloid burden and to a level between the 3- and 10-mg/kg dosages. The rates of ARIA-E with the intermediate dosage, in both ApoE4 carriers and noncarriers, might be more acceptable than those with the highest dosage. But approximately 10% of patients receiving 6 mg/kg still had to discontinue the medication because of ARIA-E.
Generally with aducanumab, as with other anti-amyloid mAbs, the issue seems to be that the compound reduces the amyloid burden, but that this result does not appear to be accompanied by meaningful clinical improvement, or (rather) a significant slowing of cognitive deterioration. And the biological effect comes at the cost of ARIA-E in an uncomfortable number of patients.
Nevertheless, two phase 3 studies (here and here) of aducanumab in early AD are recruiting patients. The primary outcome in both is global function (change in CDR-SB score), and the expected primary completion dates are 2020. Dosages to be assessed aren’t currently stipulated in the clinicaltrials.gov database.
N. B.–All P values refer to a comparison with placebo.
AAIC = Alzheimer’s Association International Conference; AD = Alzheimer disease; ARIA-E = amyloid-related imaging abnormalities, vasogenic edema; CDR-SB = Clinical Dementia Rating scale, Sum of Boxes; mAb = monoclonal antibody; MMSE = Mini-Mental State Examination; SUVR = standardized uptake value from 2 different regions on images from positron emission tomography (PET).
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.
