While Phase Ib trial data has hinted at a disease-modifying potential of aducanumab, Phase III trial success will also rest on mitigating any associated safety events.
By Maha Elsayed, Analyst
9 September 2016
I am an analyst at Datamonitor Healthcare based at the New York office, where I am part of the CNS and rare disease team...
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After a decade of trial failures in identifying a disease-modifying therapy for Alzheimer’s disease, aducanumab is the first amyloid-beta targeting drug to offer hope for the slowing of the disease progression. Biogen has shown promising data from PRIME, its Phase Ib trial of aducanumab, in which drug treatment produced significant improvements in biological efficacy (standardized uptake value ratio [SUVR]), and both cognitive (Mini-Mental State Examination [MMSE]) and functional (Clinical Dementia Rating Scale – Sum of Boxes [CDR-SB]) endpoints after one year of treatment. Although the intermediate 6mg/kg dose yielded less than conclusive results, meaning there was no clear dose-response curve on the clinical endpoints, the study’s small sample size meant that it was always likely to have some variable results. Overall, the findings were viewed as encouraging. However, high incidences of amyloid-related imaging abnormalities suggestive of sulcal effusion and parenchymal edema (ARIA-E) were observed. These side effects appeared to be dose-and genotype-dependent (43% and 55% for the 6mg/kg and 10mg/kg arms respectively among ApoE4 carriers). Considering that 10% and 35% of ApoE4 carriers in the intermediate- (6mg/kg) and high (10mg/kg)-dose arms developed ARIA-E and discontinued treatment, Biogen stratified participants in the Phase III study by dose and genotype. Biogen announced that the dosing regimen to be pursued will include 3–6mg/kg and 6–10mg/kg arms, with ApoE4 carriers excluded from receiving the highest dose. By employing these strategies to mitigate ARIA-E risk, Biogen is hoping for a smooth Phase III study without risks of patient drop-outs due to experiencing ARIA-E side-effects.
Datamonitor Healthcare’s Alzheimer’s disease: Pipeline analysis evaluates the clinical and commercial attractiveness of late-stage drugs in development for Alzheimer’s disease.
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