Aduhelm: Revisting the Phase 3 Trials and the FDA Approval Decision
Faculty Mentor
Ahmed Abu Fayyad
Major/Area of Research
Alzheimer's Disease
Description
Introduction: Age brings about mild cognitive changes, while dementia, involving memory loss, disrupts daily life. Understanding Alzheimer's Disease centers on the amyloid beta theory, with conflicting evidence and genetic influences. Aduhelm, as seen in Figure 1, is developed by Biogen and Eisai and targets brain amyloid beta for treatment. Based on the ENGAGE and EMERGE trials, Aduhelm has sparked scientific debate about its FDA approval for use in Alzheimer’s Disease.
Purpose: The cure for Alzheimer’s Disease without a proven pathogenesis? Investigating the differences in primary and secondary outcomes of Aduhelm Phase 3 Clinical Trials
Methods: A literature review was conducted to collect the Aduhelm Phase 3 trials (ENGAGE and EMERGE), as well as any relevant meta analyses and systematic reviews. All resources were identified through a computerized search of PubMed, Clinicaltrials.gov, and New England Journal of Medicine. Key search terms included: Aduhelm, aducanumab, Alzheimer’s Disease, beta-amyloid, and amyloid-related imaging abnormalities. Article types were filtered by date to focus on scientific literature after the approval of Aduhelm.
Results: Patients treated with high dose aducanumab in the EMERGE trial had significantly less progression in Alzheimer’s than those in the ENGAGE trial who were treat- ed with high dose aducanumab after 78 weeks. Additionally, amyloid PET scans showed significant decrease in amyloid in patients treated with high dose aducanumab in the EMERGE trial. As a result, EMERGE was able to meet the primary endpoint (CDR-SB) and three secondary endpoints (MMSE, ADAS-Cog13, ADCS-ADL-MCI) which demonstrated the clinical benefit of high dose aducanumab over the placebo. On the other hand, ENGAGE did not meet the endpoints that signified a clinical benefit to the use of high dose aducanumab.
Conclusion: Aduhelm’s (aducanumab) accelerated approval based on the reduction in the beta amyloid biomarker which resulted in improved cognition in patients with mild cognitive impairment due to Alzheimer’s disease, as demonstrated by the EMERGE trial. With the conflicting clinical trial data, high cost for patients, serious adverse events, and theoretical pathogenesis for Alzheimer’s disease, Aduhelm’s approval was not warranted. Another phase 3 trial should have been sanctioned before its approval to solidify/refute its clinical benefit.
Aduhelm: Revisting the Phase 3 Trials and the FDA Approval Decision
Introduction: Age brings about mild cognitive changes, while dementia, involving memory loss, disrupts daily life. Understanding Alzheimer's Disease centers on the amyloid beta theory, with conflicting evidence and genetic influences. Aduhelm, as seen in Figure 1, is developed by Biogen and Eisai and targets brain amyloid beta for treatment. Based on the ENGAGE and EMERGE trials, Aduhelm has sparked scientific debate about its FDA approval for use in Alzheimer’s Disease.
Purpose: The cure for Alzheimer’s Disease without a proven pathogenesis? Investigating the differences in primary and secondary outcomes of Aduhelm Phase 3 Clinical Trials
Methods: A literature review was conducted to collect the Aduhelm Phase 3 trials (ENGAGE and EMERGE), as well as any relevant meta analyses and systematic reviews. All resources were identified through a computerized search of PubMed, Clinicaltrials.gov, and New England Journal of Medicine. Key search terms included: Aduhelm, aducanumab, Alzheimer’s Disease, beta-amyloid, and amyloid-related imaging abnormalities. Article types were filtered by date to focus on scientific literature after the approval of Aduhelm.
Results: Patients treated with high dose aducanumab in the EMERGE trial had significantly less progression in Alzheimer’s than those in the ENGAGE trial who were treat- ed with high dose aducanumab after 78 weeks. Additionally, amyloid PET scans showed significant decrease in amyloid in patients treated with high dose aducanumab in the EMERGE trial. As a result, EMERGE was able to meet the primary endpoint (CDR-SB) and three secondary endpoints (MMSE, ADAS-Cog13, ADCS-ADL-MCI) which demonstrated the clinical benefit of high dose aducanumab over the placebo. On the other hand, ENGAGE did not meet the endpoints that signified a clinical benefit to the use of high dose aducanumab.
Conclusion: Aduhelm’s (aducanumab) accelerated approval based on the reduction in the beta amyloid biomarker which resulted in improved cognition in patients with mild cognitive impairment due to Alzheimer’s disease, as demonstrated by the EMERGE trial. With the conflicting clinical trial data, high cost for patients, serious adverse events, and theoretical pathogenesis for Alzheimer’s disease, Aduhelm’s approval was not warranted. Another phase 3 trial should have been sanctioned before its approval to solidify/refute its clinical benefit.