Getting on Target for Alzheimer’s
Biogen revitalizes hope for Alzheimer’s therapy, but their work highlights why we still need greater selectivity
Neil Cashman, James Kupiec | | Opinion
In October 2019, Biogen sent shockwaves through the Alzheimer’s community when it reanimated aducanumab, its previously dismissed therapy candidate for Alzheimer’s disease. Upon analysis of additional data supporting aducanumab’s efficacy in patients with longer term, high-dose exposure, Biogen plans to now submit the drug candidate for FDA approval in early 2020. If approved, aducanumab will be the first disease-modifying therapy for Alzheimer’s, which, as a reminder, is currently the only disease on the “top ten” causes of death without treatment.
Biogen’s surprising, but welcome, reversal not only puts hope on the horizon for a near-term Alzheimer’s treatment, it also – perhaps more importantly – revitalizes work supporting next-generation amyloid beta (Aß)-targeting candidates that can selectively target only its toxic form, beta-amyloid oligomers (AßOs).
Aducanumab gets us only partially there: 35 percent of patients experienced ARIA-E (brain swelling), revealing the critical need for improved AßO-targeting precision to achieve both greater safety and efficacy. At high doses, aducanumab binds more AßOs, supporting its efficacy, but it also binds amyloid plaque, which is off-target and triggers brain swelling. This unwanted binding of an otherwise benign clump of insoluble protein is what leads to this significant dose-limiting side effect of ARIA-E. Regrettably, definitive data demonstrating the neurotoxic role of AßOs were just becoming available when the clinical development program for aducanumab was devised.
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