Background
The FDA Oncology Center of Excellence (OCE) aims to advance the development and regulation of oncology products for patients with cancer. The Pediatric Oncology Program and Rare Cancers Program were established to facilitate and expedite drug development for pediatric and other rare cancers. OCE’s Project Catalyst connects scientific knowledge, creative insight, and medical professionals to foster early-stage product innovation, which is particularly important to address the challenges related to product development for ultra-rare cancers. In collaboration with the National Institutes of Health (NIH) and the OCE, the Foundation for the National Institutes of Health (FNIH) recently launched the design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), a new public-private partnership dedicated to accelerating the development of innovative ultra-rare cancer treatments.
For the purposes of this NOFO, the FDA OCE refers to cancers with an approximate annual incidence in the U.S. of 300 to 400 people or less as ultra-rare (a more stringent criterion compared to the threshold for a rare disease specified in the Orphan Drug Act based on a U.S. prevalence of <200,000 people).
Many of the challenges involved in drug development for ultra-rare cancers are similar to those for rare diseases and can include:
- Difficulty enrolling sufficient numbers of patients to clinical trials
- Limited financial incentives for drug development
- Insufficient understanding of the cancer pathophysiology, molecular characteristics, and natural history
- Limited or lack of timely access to molecular testing to determine eligibility for treatment with targeted therapies
- Complexities associated with designing clinical trials that are adequate to establish safety and effectiveness
Advancing technologies such as single cell multi-omic analyses have helped define some ultra-rare cancers at the molecular level, providing new opportunities for targeted drug development. Pediatric oncology has several examples of tumor types with known translocation-induced, oncogenic driver fusion proteins. Other examples of ultra-rare cancers defined today by molecular pathology include: neuroectodermal tumors, pulmonary blastoma, desmoplastic small round cell tumor (DSRCT), epithelioid sarcoma, diffuse intrinsic pontine glioma, fibrolamellar carcinoma, and malignant rhabdoid tumors.