The US Food and Drug Administration (FDA) is not amenable to changing study endpoints or sample sizes for gene therapy clinical trials but is encouraging sponsors to fill in gaps in data collection with telemedicine and remote visits.
Wilson Bryan, director of the FDA’s Office of Tissues and Advanced Therapies (OTAT) in FDA’s Center for Biologics Evaluation and Research, told a 12 May meeting of the American Society of Gene and Cell Therapy that the pandemic is prompting declining enrollment in gene therapy trials.
As a result of the shrinking enrollment, the agency is receiving a growing number of requests from sponsors to change their study parameters, such as using smaller sample sizes. Yet the agency is “hesitant” to grant these requests over fears of compromising the integrity of these trials.
**Pandemic has impacted gene therapy INDs **
Bryan said the number of gene therapy investigational new drug applications (INDs) submitted to FDA leveled off from 161 in calendar year 2019 to 160 in CY 2020, reversing a trend in increasing gene therapy IND submissions in recent years and falling far shy of the 200 plus submissions FDA had expected by 2020. Bryan attributed the flat number of submissions to fears among health care workers and patients of contracting COVID-19, with resulting “qualms” about onsite clinical visits.
The travel restrictions prompted by the pandemic are particularly hurting enrollment in gene therapy trials because many of these treatments are for rare diseases, some affecting as few as 20 to 40 patients globally. Patients must travel to the sites where the treatments are offered, and the inability to travel to clinical trial sites means onsite visits are not possible.
**Agency hesitant to endorse changing endpoints **
In response to the declining enrollment and cut down on costs tied in with lower enrollment, Bryan said that FDA has received “many” requests from sponsors to change their primary and secondary endpoints, to change study sample sizes, or to change the study duration.
Yet, the agency has been “very hesitant” to approve these requests. Bryan said that reducing sample size could mean a study “just does not have the power to provide the results that we think are reliable.” And he questioned whether reducing study duration would yield “data that is clinically meaningful.”
The agency is, however, willing to be flexible and accept alternative approaches, such as telemedicine and the use of wearable devices to monitor a patient’s reaction to the therapy. Bryan called both alternatives a “tremendous boon to the clinical trial enterprise.”
Bryan noted that “the ability to do remote monitoring to ensure safety and effectiveness generally will help move the field forward.”
When asked at the end of his presentation when the FDA would have regular face-to-face meetings again, he responded that “we are hoping to be partially open by the end of the year but we’re not sure when we’ll get back to face to face meetings.”
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