Federal health officials on Monday laid out a proposal to create a new regulatory pathway for customized treatments for people with rare diseases, including certain gene-editing therapies. In the announcement, the FDA said the draft guidance is intended to spur development of bespoke therapies that often can be tested only in a handful of patients because large studies are difficult to conduct for conditions affecting a very small fraction of people.
The proposal is built around the agency’s concept of a “plausible mechanism,” which FDA regulators would use as criteria for whether to greenlight experimental therapies. The FDA announcement specifically mentions gene editing, though agency officials said the approach could also apply to other drugs and therapies that target disease biology in a targeted way.
FDA Commissioner Marty Makary said the agency’s goal is to remove barriers and increase regulatory flexibility. “It is our priority to remove barriers and exercise regulatory flexibility to encourage scientific advances and deliver more cures and meaningful treatments for patients suffering from rare diseases,” Makary said in a release.
The announcement comes after other changes FDA leadership has discussed in recent days and weeks. AP reported that the timing follows a statement from Makary in which he said the FDA would drop a decades-old standard of requiring two clinical trials for standard drug reviews—an additional sign, in the eyes of patients and advocates for rare diseases, that FDA is trying to adjust how evidence is weighed for therapies that do not fit traditional models.
In Monday’s proposal, the FDA sought to address a core mismatch between rare-disease needs and the standard drug-approval framework. Traditionally, the agency has required drugmakers to demonstrate safety and effectiveness through clinical studies that compare treated patients with those receiving a sham treatment or alternative intervention, with larger patient enrollment generally producing stronger evidence.
For conditions that can affect only a tiny fraction of people worldwide, FDA said, companies can have little incentive to invest the millions needed for large studies that can take a decade or longer to complete and bring through the FDA approval process. Under the proposed pathway, the FDA said it would create a standardized process for authorizing experimental treatments, and it would also allow companies the possibility of commercializing them.
The FDA contrasted the proposal with its existing “compassionate use” system, which allows use of experimental drugs for people with no other medical options but is described as cumbersome and includes strict limits that prohibit companies or researchers from profiting from treatments that have not been vetted by the agency. The agency said that, by contrast, the new pathway would create a consistent route to authorization for a subset of experimental therapies.
FDA officials said the “plausible mechanism” framework would be reserved for conditions that are well understood, and where there is a plausible reason to think the therapy will act on underlying genetic or cellular biology. The FDA also said researchers would have to show that the therapy successfully targeted the patient’s genetic or biological abnormality.
The FDA’s announcement also pointed to recent research demonstrating that emerging technologies can sometimes correct individual defects in a patient’s genetic code. Last year, the FDA said, a team at Children’s Hospital of Philadelphia and the University of Pennsylvania designed a therapy using CRISPR, the gene-editing tool that won the Nobel Prize, to treat a baby born with a rare disease in which ammonia builds up in the blood.