Rare Disease Drug Repurposing.
Level 4 - case-series / case-control
Cross-sectional survey and qualitative interview study (graded by design analogy for health policy and research methodology).
PubMed 40323602 · doi:10.1001/jamanetworkopen.2025.8330
What was done
A mixed-methods study (the ROADMAP Project) surveyed and interviewed leaders of US-based rare disease nonprofit organizations (RDNPs) between September 2021 and January 2022. Surveys were completed by 147 of 698 identified RDNPs, and semistructured interviews were conducted with 34 leaders representing 25 RDNPs. Repurposing projects were categorized into stages (abandoned, early, clinical, late, or successful). Random forest models and Spearman rank correlations with Benjamini-Hochberg false discovery rate corrections were used to identify organizational and project-level variables associated with repurposing stage, alongside qualitative thematic analysis.
What was found
Among surveyed RDNPs reporting on repurposing, 42.0% (58/138) actively supported repurposing projects, spanning 94 drugs. Of these, 23 drugs met the study's success criteria: 5 received FDA approval and 18 achieved off-label use with subjective benefit. Variables significantly associated with successful project outcomes were nonprofit-supported clinical trial patient recruitment (Gini importance: 3.90; ρ = 0.50; adjusted P < .001) and provision of nonfinancial research support (Gini importance: 0.69; ρ = 0.33; adjusted P = .02). Qualitative findings were synthesized into a 5-stage repurposing framework spanning therapy enablement, identification, validation, clinical testing, and clinical endpoint attainment.
Why it matters
This study provides systematic characterization of nonprofit-led rare disease drug repurposing, demonstrating that nonfinancial resources and active trial recruitment facilitation by advocacy groups are key drivers of repurposing milestones.
Limits
The survey had a low response rate (21.1%, 147/698), introducing risk of non-response and selection bias. Data rely on self-reported organizational estimates limited to US RDNPs. Most successes (18 of 23) were defined by off-label use with subjective benefit rather than formal regulatory clearance or rigorous clinical trial endpoints.
Cited by
- partial There are approximately 14,000 human diseases that currently do not have a single approved treatment.