P211: Integrating Toxicological and Economic Evidence to Optimize Rare Disease Drug Repurposing
Poster Presenter
Michelle Mohsenin
Embase Product Manager
Elsevier United States
Objectives
To develop and apply a structured framework integrating toxicological, mechanistic, and economic evidence to improve early-stage decision-making in rare disease drug repurposing.
Method
A cross-database synthesis integrated regulatory toxicology (PharmaPendium), clinical safety (Embase), mechanistic mapping (Embiology), and bibliometric analysis (Scopus) to evaluate pirfenidone for systemic sclerosis–associated interstitial lung disease.
Results
Integrated analysis produced a cross-domain safety–mechanistic–economic profile of pirfenidone for rare disease repurposing. Regulatory toxicology data defined exposure–response relationships, no-observed-adverse-effect levels, and organ-specific toxicities relevant to chronic antifibrotic dosing. Cross-species comparisons supported clinically relevant exposure thresholds.
Clinical trial and pharmacovigilance data demonstrated reproducible safety patterns across populations, with adverse events consistent with established antifibrotic class effects. Mechanistic mapping identified substantial overlap between pirfenidone’s molecular targets and systemic sclerosis–associated interstitial lung disease (SSc-ILD) fibrotic pathways, particularly convergence in TGF-ß and PDGF signaling.
Bibliometric analysis revealed an active but fragmented translational landscape in fibrosis repurposing research, characterized by distributed collaboration networks and limited cross-domain integration.
Synthesizing toxicological risk domains with mechanistic plausibility and economic burden considerations demonstrated the feasibility and added value of structured cross-evidence integration in early repurposing evaluation.
Conclusion
This study presents a reproducible framework for integrating regulatory toxicology, clinical safety, mechanistic biology, and translational landscape evidence to support rare disease drug repurposing. Applied to pirfenidone in SSc-ILD, the approach enhances transparency, scientific rigor, and early-stage candidate prioritization.
By aligning exposure-defined safety thresholds with mechanistic plausibility and treatment burden considerations, the framework strengthens regulatory justification and informs dose optimization strategies.
The findings underscore the importance of cross-domain evidence harmonization in rare disease development, where small populations and limited trial feasibility heighten decision uncertainty. Future work will incorporate quantitative modeling of toxicity–value relationships to further support portfolio prioritization across rare therapeutic areas.
