The US Food and Drug Administration (FDA) has created a new pathway to streamline rare disease drugs through regulatory approval, allowing pharma companies to lean on smaller amounts of clinical data.
In a joint initiative between the FDA’s Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), the new process aims to reduce clinical trial hurdles often associated with rare disease patient populations and bring candidates to market faster.
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The Rare Disease Evidence Principles (RDEP) framework follows work done by ex-FDA commissioner Peter Marks to overhaul data requirements for rare diseases. In May 2024, both the CDER and CBER rolled out the START pilot programme to work out how best to facilitate rare disease drugs through development. It is unclear whether the RDEP is related to START.
Drug sponsors have until the launch of a pivotal trial to apply for the scheme. However, there are strict eligibility criteria for those wishing to place drugs into the framework. The drug must first be intended for a very small, rare disease population – generally affecting fewer than 1,000 patients in the US. The drug must also treat an inborn genetic defect that primarily drives the disease, and the disease must be progressing fast enough that it leads to significant disability or death. Finally, there must be no alternative therapies on the market for the intended indication.
For sponsors who make it onto the scheme, data requirements for approval will be easier. The FDA expects that substantial evidence of effectiveness may “generally be established based on one adequate and well-controlled study that may be a single-arm trial”.
This data must be supported by robust confirmatory evidence, such as the drug’s direct impact on the disease’s pathophysiology, relevant non-clinical models, clinical pharmacodynamic data, case reports, and expanded access data.
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By GlobalDataFDA Commissioner Marty Makary said: “Drug developers – and the patients they hope to treat – deserve clear, consistent information from the FDA.
“These principles ensure that 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.”
The framework comes after US health secretary Robert F Kennedy Jr promised pharma companies more fast-track pathways for rare disease drugs in June 2025. Recent federal funding cuts and a slackened legislative process have raised concerns among researchers, patient advocates, and biotechs about the future of rare disease research in the US.
Analysts praised the policy for advancing therapies for rare diseases, though they cautioned that single-arm trials are already being used for drugs in development.
GlobalData Life Sciences research analyst Cyrus Fan said: “On paper, it would appear positive for the biopharma industry, and the heightened flexibility for rare disease drugs may mean faster approvals for ultra rare diseases.”
William Blair analyst Sami Corwin said: “While we are encouraged that the FDA is continuing to exhibit flexibility in evaluating gene therapies for rare diseases, it remains unclear what tangible impact the framework will have on the development process and approval timeline, given several gene therapies in development are already utilising single-arm trials for registration.
She pointed to Neurogene’s NGN-401, Rocket’s RP-A501, and Lexeo’s LX2006, amongst others, as therapies already undergoing single-arm trial evaluations.
Corwin added: “In addition, given the restrictions on patient size for the program, most therapies in development won’t be eligible to apply. However, the framework could benefit companies developing platform therapies that could address rare diseases caused by a mutation in one of several genes, assuming a different product is needed for each genotype, by offering regulatory consistency and greater predictability.”
