By Fineline Cube 
The U.S. Food and Drug Administration (FDA) today issued the Rare Disease Evidence Principles (RDEP), a new set of guidelines designed to streamline the regulatory review of treatments for ultra‑rare conditions. The principles are a joint effort of the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) and focus on delivering speed and predictability for therapies that target diseases marked by extremely small patient populations and genetic defects.
What RDEP Brings to the Table
| Feature | Description |
|---|---|
| Single Adequate Study | Approval may be based on one well‑controlled trial, complemented by additional evidence. |
| Robust Confirmatory Evidence | Accepts mechanistic data, biomarkers, non‑clinical models, pharmacodynamic readouts, case reports, expanded‑access data, or natural‑history studies. |
| Independent of Orphan Designation | A drug reviewed under RDEP is not automatically granted orphan status, and the orphan eligibility process remains unchanged. |
Key Evidence Types Accepted Under RDEP
- Strong mechanistic or biomarker evidence that links target engagement to clinical benefit.
- Data from relevant non‑clinical models demonstrating safety and efficacy in disease‑specific contexts.
- Clinical pharmacodynamic data that confirms target modulation in patients.
- Case reports, expanded‑access data, or natural‑history studies that provide real‑world insight into safety and effectiveness.
How RDEP Helps Sponsors
- Reduced Development Time – By allowing a single pivotal study plus confirmatory evidence, sponsors can bring therapies to patients faster.
- Greater Predictability – Clear guidance on acceptable evidence types helps sponsors design trials that meet FDA expectations.
- Flexibility for Rare Populations – RDEP acknowledges the unique challenges of enrolling patients with extremely low prevalence, permitting alternative data sources.
Next Steps for the FDA Community
- Submission Guidance – Sponsors are encouraged to submit a RDEP Request for Review early in development to receive tailored feedback.
- Orphan Designation Process – While RDEP does not confer orphan status, sponsors may still pursue Section 526 designation if appropriate.
- Ongoing Dialogue – The FDA will host webinars and workshops to clarify how RDEP applies across therapeutic areas.-Fineline Info & Tech