As the FDA’s accelerated approval program faces increased scrutiny from lawmakers, regulatory experts tackled the hot-button issue in a panel discussion at this year’s Drug Information Association (DIA) annual meeting in Chicago. According to the panel, several key reforms, including more requirements for post-market studies, could address major concerns with the pathway while maintaining its benefit for patients.
“I think we forget what the standard really means. Is it perfect? No. Is it validated? Actually, no. It's just reasonably likely,” Kristin Van Goor, Vertex Pharmaceuticals’ head of North American regulatory policy, said of the pathway’s purpose during the discussion.
The panel, “Is it Time to Change the Accelerated Approval Pathway?” examined ways to streamline and enhance the pathway in light of the controversy over FDA’s approval of Biogen’s Alzheimer’s drug Aduhelm last year, which sparked questions over the pathway’s intended use.
“I think it's worth revisiting the guardrails for the pathway that keeps us away from it being an incentive. Those are things like getting the confirmatory studies underway and getting those completed in a timely manner,” Van Goor said during the panel.
“We all really need to work together and communicate what the expectations are.”
Kristin Van Goor
Head of North American regulatory policy, Vertex Pharmaceuticals
Van Goor and fellow panel member Jeff Allen, president and CEO of the nonprofit Friends of Cancer Research, argued for the clarification of such guardrails, and the implementation of requirements for drug developers to plan post-market confirmatory clinical trials prior to approval.
“I don't have a lot of sympathy for this. I think you have to know what you're doing. You have to know what your strategy is to develop the drug, get the evidence and get patients access,” Van Goor suggested. And while developing a strategy for a biomarker might be more difficult than for an intermediate endpoint, not having a plan is “hard to explain” for a drug developer, she said.
Van Goor and Allen also agreed that any regulations related to the length of confirmatory trials should remain flexible.
“As we think about the actual time it takes to complete an entire living clinical study, it's not going to be instantaneous results. That's not to say that there shouldn't be sufficient due diligence in order to complete the confirmatory trials. But I think it's important to recognize that there is a time element in order to get to these full endpoints from a confirmatory standpoint, and that's sort of the point of the program,” Allen argued.
Van Goor further suggested that the time needed to complete a confirmatory trial may differ widely depending on the type of drug or indication area. For instance, she suggested that cell and gene therapies will require longer timelines because “you're intervening even closer to the root of the problem and it's just going to take longer to make the connection to a long-term clinical outcome that's meaningful.”
Meaningful measurements
As drug developers seek to use the accelerated approval program for disease areas beyond oncology, Allen said stakeholders must come to an agreed-upon standard to measure the success of a drug.
“The research community can come together and help determine what the appropriate level of change and [the] measure a biomarker needs to be in order to be clean, clinically meaningful and then apply that consistently in clinical trials,” he said.
The success of oncology treatments in the accelerated approval process, for instance, is measured by a 30% reduction in the size of the largest tumor, he noted. A similar measure for a meaningful reduction in beta amyloid plaques has not been identified to determine the success of certain Alzheimer’s drugs.
And finding an adequate solution requires collaboration between all stakeholders, he and Van Goor told attendees.
“This can't be a problem for drug developers to solve because they want to get their drug approved. This can't be a problem for the patient community to solve because they need treatment options. And this can't be just a problem for the regulators to solve and articulate a standard,” Van Goor said. “I think we all really need to work together and communicate what the expectations are.”
