FDA to modernise review process for developers of ultra-rare diseases

The US Food and Drug Administration (FDA) is proposing a new procedure for rare disease clinical trials to help expedite their review.

The Rare Disease Evidence Principles (RDEP) process is intended to assure trial sponsors that the FDA’s assessments will encompass additional supportive data.

The small patient populations associated with rare diseases has historically challenged pharma companies to produce substantial safety and efficacy data from products, even when they run multiple traditional clinical trials.

Developed and implemented jointly by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), the RDEP seeks to address some of the uncertainties of rare disease drug development.

Approval and eligibility under the new Rare Disease Evidence Principles (RDEP) process

Alongside one adequate and well-controlled study, approval via the RDEP may be based on robust confirmatory evidence, such as:

• Strong mechanistic or biomarker evidence
• Evidence from relevant non-clinical models
• Clinical pharmacodynamic data
• Case reports, expanded access data, or natural history studies.

Sponsors are eligible for the RDEP if their therapies address the genetic defect of the intended rare disease. Specifically, the drug should target a patient population of approximately fewer than 1,000 patients with significant unmet medical need, and for whom no adequate alternative treatments are available. 

Developers can apply for review under the RDEP process as part of a formal meeting request and any time before launching a pivotal trial.

Drugs approved through this process may require further data as post-marketing requirements, according to the FDA.

FDA Commissioner Dr Marty Makary said: “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.”    

As the FDA continues its efforts to streamline drug development processes, the agency earlier this week agreed for the first time to file a FDA biosimilar application for a monoclonal antibody biosimilar without requiring clinical testing.