Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019
In a perspective, the authors call for a third, phase III trial with high‐dose aducanumab to be conducted as its efficacy as a treatment for cognitive dysfunction in Alzheimer's disease cannot be proven by clinical trials with divergent outcomes.
Source:
Alzheimer's & Dementia
SPS commentary:
Biogen submitted a Biologics License Application to the FDA in July and it has been under review ever since. The European Medicines Agency also recently began their review.
Two large phase III clinical trials were stopped prematurely by Biogen; one was trending positive while the other showed no benefits from aducanumab, investigational human monoclonal antibody. The company asserts that on the basis of post hoc analyses showing subsets of participants receiving sufficiently high doses of aducanumab demonstrated benefits in both trials, there was a sufficient efficacy signal to justify a new drug application as a treatment for Alzheimer's disease.
The authors of the perspective say that in contrast, they have identified alternative accounts for the apparent drug benefits in post hoc subgroups that are unrelated to dose effects. Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits.
Reuters has reported that briefing documents released ahead of a meeting on Friday suggests “a positive Advisory Committee vote, which bodes well for approval.”
Patient advocacy groups have argued that aducanumab needs to be approved due to that large unmet medical need. The chief science officer at the Alzheimer’s Drug Discovery Foundation said “If a third trial is recommended then years could go by ... while people aren’t granted access to the drug.”