FDA Unveils New Policy to Accelerate Rare Disease Treatments

The Food and Drug Administration Monday unveiled the details of a new policy designed to make it easier and quicker for patients with very rare diseases to get cutting-edge treatments.

The new guidance would enable the agency to approve new treatments for rare diseases based on evidence for a "plausible mechanism" for how the treatment would work. The policy aims to speed the use of state-of-the-art technologies like gene-editing to create treatments tailored to individual patients suffering from diseases that are so rare that it would be difficult if not impossible to conduct a traditional study first.

"For decades families heard the same thing: There are not enough patients. The approval will take too long. You just have to wait for the science to catch up with your child," Health and Human Services Secretary Robert F. Kennedy Jr. said at a briefing announcing the proposed new policy. "That ends today. Individualized medicine is no longer theoretical."

"Historically, rare diseases at the FDA have been an afterthought," added FDA Commissioner Marty Makary said at the briefing. "We've come a long way."

The new approach, outlined broadly in November, would apply to diseases where there is a plausible expectation that the treatment would work, such as an understanding of the genetic defect causing the disorder and how the treatment would address it.

"Today is a very exciting day for patients with very rare diseases," said Dr. Tracy Beth Høeg, the director of the FDA's Center for Drug Evaluation and Research, at the briefing.

Scientists have started developing gene-editing treatments like CRISPR to help patients suffering from genetic blood disorders such as sickle cell disease, and are studying experimental gene-editing therapies for other diseases, including cancer, inherited high cholesterol and some forms of genetic blindness.

But many doctors, patients and their families have been frustrated because pharmaceutical companies don't have a strong economic incentive to create gene-editing treatments for extremely rare disorders. Altogether there are thousands of conditions that potentially could be cured by gene-editing. The FDA estimates that 30 million Americans suffer from a rare disease.

In response, scientists have been trying to solve the problem by creating a template for groups of rare conditions that are similar enough that a gene-editing treatment for one could be easily adapted for others. That way each case wouldn't have to go through a long regulatory approval process, which could make it more affordable and practical.

The new FDA policy, which is designed to address that concern, was prompted in part by a Pennsylvania baby treated at the Children's Hospital of Philadelphia. Doctors at CHOP saved the infant, who was born with a very rare but devastating genetic liver disorder, by producing a gene-editing treatment targeting his specific genetic defect. The same approach could be adapted to other, similar conditions.

"We realized we can do this over and over again, individualizing the therapy for many patients," said Dr. Kiran Musunuru, a professor for translational research at the University of Pennsylvania at the briefing. Musunuru helped develop the treatment for that baby. "It will allow doctors to treat many, many patients."

"We need these innovative regulatory frameworks that will allow us to efficiently evaluate if these treatments are safe and if they work," agreed Dr. Rebecca Ahrens-Nicklas, one of the CHOP doctors who treated the baby, at the briefing.

The new FDA policy, which could also be applied to other technologies, such as antisense oligonucleotides, was praised by many outside experts.

"Today's guidance is the best imaginable 'ready, set, go!' for the field of personalized gene editing as a therapy," wrote Fyodor Urnov of the University of California, Berkeley, in an email to NPR. "To hear HHS leadership say: 'a disease with 100 causing mutations will no longer require 100 clinical trials' sounds like a veritable 'Ode to Joy' because it means we will be able to treat children faster and more affordably."

Others agreed, but also expressed concern about how widely the policy would be applied.

"The plausible mechanism policy seems like it's addressing a real problem," says Rachel Sachs, a law professor at Washington University in St. Louis who has raised questions about the approach. "The concern is that the plausible mechanism pathway could be expanded into disease areas where there are common diseases and traditional trials are feasible and that it wouldn't be necessary to go through this pathway."