Researching neurodegenerative diseases often feels like an unwinnable battle against biology. Despite decades of effort, we still have no means for reversing the effects of these devastating disorders. Understandably, the lack of treatment options for a rapidly growing population has led to intensifying anxiety and frustration among patients who rely on scientific progress for their survival.
This pressure to find a cure can have mixed effects on drug development, a fact that was made clear during the closely watched approval process for two medications targeting neurodegenerative diseases: aducanumab and tofersen.
In 2021, the United States Food and Drug Administration (FDA) approved the use of aducanumab as a treatment for Alzheimer’s disease, disregarding significant doubts as to the drug’s efficacy. Aducanumab was tested in two Phase III trials, only one of which met its primary endpoint goals for success. Still, aducanumab was fast-tracked for approval, putting many physicians in an uncomfortable position. In a poll conducted in June of 2021, 87% of the physicians surveyed disagreed or strongly disagreed with the FDA’s decision, and nearly half expressed concern about being asked to prescribe an ineffective or potentially harmful drug to desperate patients willing to grasp at anything approximating hope. To some, the approval of aducanumab did not represent a major milestone for patients, but rather a cynical manipulation of the health care system for personal profit.
Sometimes, though, a clinical trial fails not on the merits of the drug being tested, but because of a miscalibrated trial design; such was the case with tofersen. A treatment for amyotrophic lateral sclerosis (ALS), tofersen, like aducanumab, did not initially meet its primary endpoints within the timeframe of the trial. However, the Phase III data were encouraging, leading to an open-label extension (OLE) lasting 52 weeks, almost twice the length of the original 28-week trial. In an OLE, all trial participants are given the option to take the active drug as opposed to the placebo. Over this longer time frame, tofersen provided significant benefit, and in April of this year, the medication was approved by the FDA. The FDA’s decision came after the ALS Association submitted a statement calling for tofersen’s accelerated approval, stating, “Our community cannot wait.”
Tofersen is not the only neurodegeneration-targeting drug to be granted an OLE, a trend that can be attributed in part to a strengthening sentiment that OLEs and other inclusively designed trials prioritize patients, allowing more people to have access to promising nascent therapeutics. Moving to a patient-focused model of research is a positive development, and it ought to extend beyond the clinic. For scientists in the lab, contact with patients reinforces the real-world impact of their research. More importantly, though, increasing communication between researchers and patients provides those suffering with the disease a sense of agency, demystifying the process of creating and evaluating the medicines they may one day be taking.
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