Rare Disease Evidence Principles (RDEP) - new FDA principles for evaluating orphan drugs

The FDA has introduced a new process, the Rare Disease Evidence Principles (RDEP),, to simplify and expedite the approval of orphan drugs for extremely rare genetic diseases.

Eligibility Criteria:

• the disease occurs in very few patients (usually less than 1,000 in the U.S.);

• is caused by a known genetic defect;

• has a rapidly progressive course with high disability or mortality;

• has no adequate treatment options.

Approach to evidence:

A single clinical trial (including an uncontrolled trial) may be sufficient for registration if it is supported by convincing additional data. As evidence, the FDA will consider:

biomarkers and data on the effect on the pathophysiology of the disease,

• results of preclinical models,

• pharmacodynamics,

• clinical cases,

• natural history studies or external control groups.

Review process:

The application is submitted before the start of the pivotal study. The decision on inclusion is made by the FDA jointly with the Rare Disease Policy and Portfolio Council (RDPPC). Acceptable sources of evidence are agreed upon at an early stage, although additional obligations after approval (additional studies, observation) are possible.

Important:participation in RDEP is not directly related to the orphan designation procedure; a separate application procedure is maintained for this.

Thus, RDEP formalizes the possibility of approving orphan drugs based on a single study and a set of confirmatory data, which is especially important for rare genetic diseases, where traditional large RCTs are impossible.

Read more: FDA advances rare disease drug development with new evidence principles (https://www.fda.gov/news-events/press-announcements/fda-advances-rare-disease-drug-development-new-e...)