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  1. Accelerating Rare disease Cures (ARC) Program

Rare Disease Regulatory Science Research

CDER’s ARC Program | Center for Drug Evaluation and Research

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Decorative image for Rare Disease Regulatory Science Research

CDER’s Accelerating Rare disease Cures (ARC) Program and Rare Diseases Team (RDT) support and lead research to advance rare disease drug development, inform product review, and improve policy related to rare disease therapeutics. The RDT engages in internal (e.g., for fellows mentored by the RDT) and external (e.g., through research contracts) research projects that utilize regulatory science to identify broader challenges and potential solutions that may inform rare disease drug development across therapeutic areas.

External Regulatory Science Research 

ARC’s RDT supports external regulatory science projects through ARC-funded Broad Agency Announcement (BAA) research contracts. These contracts aim to advance rare disease drug development and inform regulatory review through the development of innovative methods and novel research tools. ARC-funded BAA research contracts include:

Seamless Design for Multicomponent Endpoints for Drug Development in Rare Diseases 

The aim of this project, conducted with the University of Michigan Department of Biostatistics, is to assist statisticians working on clinical trial design and analyses for small samples to support regulatory submissions in rare diseases. The project will utilize multicomponent endpoints, interim analyses, and Bayesian joint modeling to improve trial efficiency and robustness.

Advancement of Drug Development Tools for Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)

This project, conducted by Wake Forest University and the Critical Path Institute, aims to leverage the ADTKD patient registry at Wake Forest School of Medicine to ingest, curate, and map clinical phenotyping data. These data will then be used for the development of disease progression models that incorporate fluid and imaging biomarker covariate measurements of interest.

  • Bleyer AJ, Kidd KO, Živná M, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease: A Review. Am J Kidney Dis. 2025 Aug 18:S0272-6386(25)00975-8. doi:10.1053/j.ajkd.2025.05.015. Epub ahead of print. PMID: 40835155. 
  • Ramesh, S. S., Rogge, M., Kidd, K. O., Williams, A. H., Yoon, D. Y., Roignot, J., Blakeslee, K., Bleyer, A. J., Sr, & Kim, S. (2025). Quantifying clinical and genetic factors influencing rate and severity of autosomal dominant tubulointerstitial kidney disease progression. Journal of pharmacokinetics and pharmacodynamics,52(4), 41. doi.org/10.1007/s10928-025-09989-0
  • Elhassan, E. A. E., Cormican, S., Osman, S. M., Sarihan, S., Teltsh, O., Poynton, F. E., Griffin, M. D., Casserly, L., McCann, E., Bleyer, A. J., Sr, Kmoch, S., Živná, M., Benson, K. A., Cavalleri, G. L., & Conlon, P. J. (2025). Characterization of Monogenic Kidney Disease in Older Patients With CKD.Kidney international reports,10(7), 2140–2152. doi.org/10.1016/j.ekir.2025.04.017
  • Schott C, Alajmi M, Bukhari M, et al. Genetic Testing in Adults over 50 Years with Chronic Kidney Disease: Diagnostic Yield and Clinical Implications in a Specialized Kidney Genetics Clinic. Genes (Basel). 2025;16(4):408. Published 2025 Mar 31. DOI:10.3390/genes16040408
  • Schott C, Arnaldi M, Baker C, et al. Implementation of a Kidney Genetic Service Into the Diagnostic Pathway for Patients With Chronic Kidney Disease in Canada.Kidney Int Rep. 2024;10(2):574-590. Published 2024 Nov 13. doi:10.1016/j.ekir.2024.11.004
  • Bazua-Valenti S, Brown MR, Zavras J, et al. Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors.J Clin Invest. 2024;134(24):e180347. Published 2024 Dec 16. doi:10.1172/JCI180347

Internal Regulatory Science Research

ARC and the RDT also support internal research conducted by FDA staff and fellows from the Oak Ridge Institute for Science and Education (ORISE) fellowship program. ARC-supported internal research has included:

Pivotal Trial Characteristics of Rare Disease Drug Approvals

This project examined clinical trial characteristics that were the basis of drug approvals for rare diseases between 2013 and 2022. It found that both biomarkers and clinical outcomes were commonly used as primary efficacy endpoints in rare disease trials. The choice of primary endpoint varied by therapeutic area, approval pathway, and understanding of disease etiology.


Hong K, Nugent B, Bandukwala A, Schuck R, Tomita Y, Pepe S, DoiM, Winiecki S, Lee KJ. Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022. Clin Trials. 2025Jun;22(3):352-360. doi: 10.1177/17407745241309318. Epub 2025Jan 25. PMID: 39862118.

Confirmatory Evidence

This project examined the types of confirmatory evidence (CE), utilized between 2020 and 2023, for rare disease drug approvals based on a single adequate and well-controlled trial plus CE. Although the types of CE varied, mechanistic or pharmacodynamic evidence supported 77.5% of rare disease marketing applications approved based on one adequate and well-controlled trial plus CE.


Nugent BM, Ramamoorthy A, Pippins JR, Pepe S, Doi M, Thomas A, Bagheri B, Welsh C, Madabushi R, Lee KJ. Confirmatory Evidence Used in Non-Oncologic Rare Disease New Molecular Entity Marketing Applications Approved by FDA, 2020-2023. ClinPharmacol Ther. 2025 Jun;117(6):1627-1631. doi: 10.1002/cpt.3630.Epub 2025 Mar 20. PMID: 40111209.
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