Proposed FDA Process Seeks to Increase Speed and Predictability of Ultra-Rare Disease Therapy Reviews

Rare Daily Staff

The U.S. Food and Drug Administration has unveiled a set of principles intended to improve the speed and predictability of reviews of therapies for ultra-rare diseases with significant unmet needs that are driven by a known genetic defect.

The so-called Rare Disease Evidence Principles process will provide sponsors with clearer guidance on the types of evidence that can be used to demonstrate substantial evidence of effectiveness.

Sponsors may apply to the process any time before the launch of a pivotal trial. To be eligible, therapies must specifically address the genetic defect in question and target a very small, rare disease population or subpopulation—generally fewer than 1,000 patients in the United States—facing rapid deterioration in function leading to disability or death, for whom no adequate alternative therapies exist.

The Rare Disease Evidence Principles—developed jointly by the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research—are designed to address the uncertainties of rare disease drug development by assuring sponsors that reviews will consider additional supportive data.

Because patient populations are so small, it can be difficult to generate substantial evidence of safety and efficacy through multiple traditional clinical trials for ultra-rare diseases. Instead, rare disease drug developers and the FDA must work together to identify alternative methods for meeting legal requirements that are both rigorous and viable for these populations.

Approval under the process may be based on one adequate, well-controlled study plus robust confirmatory evidence, which may include strong mechanistic or biomarker evidence; data from relevant nonclinical models; clinical pharmacodynamic data; case reports; expanded access data; or natural history studies.

Drugs approved using this pathway may face additional postmarketing requirements to further ensure safety and effectiveness.

“Drug developers—and the patients they hope to treat—deserve clear, consistent information from the FDA,” said FDA Commissioner Marty Makary. “These principles ensure that the FDA and sponsors are aligned on a flexible, common-sense approach within our existing authorities, and that we incorporate confirmatory evidence to give sponsors a clear, rigorous path to bring safe and effective treatments to those who need them most.”

Photo: FDA Commissioner Marty Makary