FDA Signals New Fast Track for Personalized Rare-Disease Therapies

The FDA is laying the groundwork for a faster, more predictable path to personalized rare-disease treatments — a shift that could reshape how ultra-rare genetic conditions are treated and how developers bring bespoke therapies to patients. The move follows the high-profile case of a newborn who received a custom gene-editing therapy earlier this year and reflects the agency’s effort to modernize approval standards as individualized medicines advance.

In an article published last week in the New England Journal of Medicine, FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research Director Vinay Prasad described a “plausible mechanism pathway” that would give drug developers new guidelines for getting ultra-rare medicines approved.

“Nearly 30 years after the sequencing of the human genome, bespoke therapies are close to reality,” Makary and Prasad wrote. “The FDA will work as a partner and guide in ushering these therapies to market, and our regulatory strategies will evolve to match the pace of scientific advances.”

The approach grew from the case of Baby K.J., a newborn diagnosed with a severe metabolic disorder in his first 48 hours of life. His doctors custom-built a gene-editing therapy targeting his specific genetic mutations, and the FDA processed the paperwork in one week. After treatment, the infant could eat more protein and needed only half his original dose of a medication that helps clear ammonia from his blood.

RELATED: What Richard Pazdur’s New Role Means for FDA Drug Reviews

Five Requirements for Approval

The pathway requires companies to show five things:

• A specific genetic or molecular problem. The FDA will limit this pathway to diseases where the exact biological cause is understood, not conditions diagnosed by a collection of symptoms.

• The treatment must directly fix or work around that genetic problem.

• A clear picture of how the disease normally progresses in untreated patients.

• Evidence that the treatment reached its target, using animal, lab, or patient data when feasible.

• Patients must clearly get better. In progressive diseases, the FDA will look for consistent improvement. In conditions that flare and fade, the agency will want to see long periods without symptoms.

Once a company shows success in several consecutive patients using personalized versions of the same platform, the FDA says it will move toward granting marketing authorization. If approval is granted, companies must collect real-world evidence to confirm the treatments continue working and do not cause unexpected problems. While this pathway will prioritize fatal childhood diseases, Makary and Prasad said it could eventually apply to more common conditions.

RELATED: How to Evaluate the Market Size for a New Biotech Company (and Build a Biotech TAM You Can Defend)

The Industry Response

Biotech lawyers and patient advocates responded positively to the news, though some want more details.

David Barrett, CEO of the American Society of Gene and Cell Therapy, wrote in a LinkedIn post that the approach “has the potential to open therapeutic options for thousands and make universal access to [cell and gene therapy] a reality.”

Julia Vitarello, whose daughter Mila received one of the first custom therapies, said the announcement moves the field closer to treating children at scale. Nearly eight years after Mila’s treatment, “we are closer than ever to seeing individualized medicines be delivered at scale,” Vitarello wrote.

Peter Pitts, president of the Center for Medicine in the Public Interest, questioned whether enough details are available to spur more high-risk development. “The Plausible Mechanism Pathway is a striking example of outside-the-box thinking, but important questions remain,” he wrote.

James Valentine, an FDA lawyer at Hyman, Phelps and McNamara, called the approach “common-sense regulatory thinking.” “We’ve long been asking for more tools in our toolbelt to address the unique challenges in rare-disease drug development,” he wrote. “Even if not a perfect or fully flushed-out program, this represents an important step.”

The FDA officials acknowledged critics who say existing regulations already handle these therapies. But patients, parents, researchers, and developers have told the agency that current rules are onerous and stifle innovation.

“For patients and families, there is no time to wait,” Makary and Prasad said.