ENGAGE and EMERGE: Truth and consequences?

Area of Science:

• Neurology
• Pharmacology
• Clinical Trials

Background:

• The anti-amyloid drug aducanumab has been evaluated for treating mild cognitive impairment (MCI) and early dementia.
• Recent clinical trials, EMERGE and ENGAGE, yielded controversial findings regarding aducanumab's efficacy.

Purpose of the Study:

• To analyze the controversial results of the EMERGE and ENGAGE clinical trials for aducanumab.
• To discuss the implications of these findings for anti-amyloid therapies and the amyloid hypothesis in Alzheimer's disease (AD).

Main Methods:

• Review of 18-month clinical trial data from EMERGE and ENGAGE studies in MCI and early dementia patients.
• Analysis of differing opinions from the FDA Advisory Committee, FDA Office of Neurological Drugs, and statisticians.

Main Results:

• The ENGAGE trial demonstrated no significant benefit from aducanumab.
• The EMERGE trial showed no initial benefit, but a significant positive benefit emerged with longer follow-up in high-dose groups.
• Conflicting assessments from regulatory bodies and statisticians complicate the interpretation of trial outcomes.

Conclusions:

• The mixed results and regulatory disagreements raise questions about aducanumab's approval status and future clinical trials.
• The findings have substantial implications for the broader field of anti-amyloid drug development and the underlying amyloid cascade hypothesis for AD.