Comment from Open Source Medicine

Public Comment - Docket No. FDA-2026-N-4492 Drug Repurposing for Unmet Medical Needs; Request for Information Submitted by: Matthew Halma, PhD Candidate, Executive Director, Open Source Medicine Foundation (OSMF) ORCID: 0000-0003-2487-0636 Contact: [mhalma@opensourcemed.info](mailto:mhalma@opensourcemed.info) Date: July 12, 2026 Declaration: OSMF is a non-commercial organization with no financial interests in any referenced drugs or patents. All tools and data described are open source and offered as a public good. Summary The docket correctly identifies the central challenge: without market exclusivity, private sponsors rarely fund the well-controlled trials required for new indications under section 505(d). The evidence gap for repurposed generic drugs is primarily economic rather than scientific. OSMF has developed decentralized clinical trial infrastructure (VitalScan4PACVS), the RepurpOS candidate discovery platform, and a prospective dengue biobank that substantially reduce the cost of generating rigorous evidence. Proposal: Develop a non-commercial, decentralized, shared-placebo adaptive platform trial evaluating approved metabolic modulators for infection-associated chronic conditions (IACCs), with treatment arms guided by metabolomic phenotyping. Topic 1 - Priority Areas I support the five proposed priority areas and recommend two additions plus one methodological refinement. Addition 1: Infection-associated chronic conditions (IACCs), including ME/CFS, Long COVID, PACVS, post-Lyme, post-dengue, and post-EBV syndromes. These conditions affect large populations, lack approved therapies, rely primarily on supportive care, and have numerous promising generic candidates. They fit naturally within a metabolic priority area because of recurring findings of mitochondrial and immunometabolic dysfunction. Addition 2: Neglected tropical diseases, including dengue and its chronic sequelae. Methodological refinement: Prioritize diseases based on therapeutic adequacy rather than prevalence alone. FDA could adopt an explicit measure of whether existing treatments meaningfully alter disease outcomes. OSMF is developing an open therapeutic adequacy database and would gladly contribute it. Topic 2 - Candidate Therapies VitalScan4PACVS is a 90-day metabolic protocol containing ten agents targeting nitric oxide bioavailability and mitochondrial function: L-glutamine, L-citrulline, creatine monohydrate, L-serine, L-arginine, N-acetylcysteine, acetyl-L-carnitine, taurine, vitamin C, and NMN. Several components are already FDA-approved drugs available as generics (for example, Endari, Carnitor, Acetadote, and ascorbic acid) but lack commercial incentives for new indications. Existing evidence, including the Tosato et al. randomized trial of L-arginine plus vitamin C in Long COVID, together with studies of taurine, creatine, serine, and acylcarnitines, supports further evaluation through an adaptive platform trial. Additional candidates include pyridostigmine, low-dose naltrexone, ivabradine, midodrine, and fluvoxamine. RepurpOS also generates ranked, mechanism-based candidates from public biomedical databases. Topic 3 - Candidate Identification RepurpOS was developed specifically to support systematic drug repurposing through: * Therapeutic adequacy scoring * Integration of Open Targets, ChEMBL, and HPO * FDA-aligned evidence tiering * Disease-specific pipelines for IACCs and neglected tropical diseases * DARE-SAFE real-world evidence evaluation OSMF offers unrestricted access to the platform and source code for FDA and NIH use. Topic 4 - Barriers and Opportunities The greatest barrier remains the cost of clinical trials in the absence of commercial incentives. Decentralized designs substantially reduce these costs by enabling remote enrollment, objective digital endpoints, and biomarker-guided patient stratification. OSMF's prospective dengue biobank combines longitudinal clinical follow-up with metabolomic profiling to identify pathways associated with chronic disease after infection. A shared-placebo adaptive platform trial would efficiently evaluate multiple generic therapies across related IACCs while minimizing cost and maximizing statistical efficiency. Recommended FDA Actions * Clarify pathways for non-commercial supplemental applications. * Publish acceptable decentralized evidence standards. * Apply MODERN authorities to appropriate labeling updates. * Support adaptive platform trials rather than isolated studies. * Expand registries capturing off-label treatment outcomes. Offer OSMF offers VitalScan4PACVS infrastructure, RepurpOS, therapeutic adequacy resources, and dengue biobank expertise at no cost. We would welcome the opportunity to brief CDER staff and serve as a non-commercial coordinating center. Respectfully submitted, Matthew Halma, PhD Candidate Executive Director Open Source Medicine Foundation