Trial-and-Error Approach With Aducanumab: Hermona Soreq, PhD

"It is complicated, but the brain is a very complex organ. It’s much more challenging than a tumor in one particular sector. But I believe in science, science has a lot of power. I have been thrilled for a year now because RNA therapeutic is not a joke anymore. It has been done. But that again was developed in 20 years.”

The FDA’s decision to approve aducanumab (Aduhelm; Biogen), the first disease-modifying therapy for the treatment of Alzheimer disease (AD), came with much controversy due to its unusual approval pathway. In March 2019, Biogen discontinued 2 phase 3 clinical trials evaluating the anti-amyloid agent–EMERGE (NCT02484547) and ENGAGE (NCT02477800), as well as a phase 2 safety study, EVOLVE (NCT03639987), which were later used for supporting data.

Aducanumab’s tumultuous journey didn’t stop there. In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee ultimately voted to not recommend regulatory approval following the drug’s original biologics license application. The group noted that the findings from EMERGE did not provide enough evidence for the effectiveness of aducanumab in AD. Despite inconsistencies in data, the FDA’s final decision reflected aducanumab’s ability to remove amyloid from the brain and slow disease progression was enough to earn approval with a need for confirmatory phase 4 study.

Hermona Soreq, PhD, professor of Molecular Neuroscience, Edmond and Lily Safra Center for Brain Sciences told NeurologyLive that she feels comfortable enough to use the drug, even with its inconsistencies. She sat down for an interview to explain why even a small clinical benefit may be useful for some patients, and why aducanumab’s safe profile should encourage clinicians to feel less guilty about taking a trial-and-error approach.