FDA advances Drug Repurposing to address Unmet Medical Needs

FDA is opening a public docket to solicit stakeholder input on advancing drug repurposing to address unmet medical needs, with particular emphasis on FDA-approved drugs where there appears to be no commercial incentive to pursue a new use via a supplemental NDA. FDA is specifically requesting comments on priority disease areas for repurposing efforts and on potential repurposing candidates to inform how the Agency identifies, prioritizes, and evaluates candidates going forward. Comments are due by June 11, 2026.

Background

Drug repurposing is characterized as finding new therapeutic uses for FDA-approved drugs where the new use can be supported by safety and effectiveness data, potentially accelerating availability of treatments by leveraging established safety profiles. FDA notes prior stakeholder work (e.g., workshops and white papers) and highlights that the September 2025 “Make Our Children Healthy Again” strategy report directs FDA to work with NIH to identify repurposing opportunities and align pathways to approval through collaborative clinical trial designs. FDA distinguishes between cases where a new use is commercially viable—leading sponsors to file supplemental applications under FD&C Act 505(b)—and cases with low or no commercial incentive (e.g., discontinued brands or generic-only markets), where FDA may rely on existing legislative and regulatory mechanisms to encourage or drive labeling updates when supported by adequate evidence. 

Operational precedent/examples

• Project Renewal (FDA OCE): uses publicly available evidence to update labeling for older oncology drugs; examples: capecitabine, temozolomide, fludarabine phosphate (updated indications, dosing, safety).
• FDA-initiated systematic literature analyses followed by Federal Register actions encouraging supplements; examples include labeling changes for doxycycline/penicillin G procaine (anthrax exposure) and Ca‑DTPA/Zn‑DTPA (certain radiation exposures).
• Recent example of literature-supported supplemental approval: leucovorin calcium tablets for cerebral folate transport deficiency (CFTD‑FOLR1), based on systematic review (case reports + mechanistic data) with FDA collaboration on labeling content.

Topics for Public Input 

FDA focuses on FDA-approved drugs with no apparent commercial interestin filing supplements, prioritizing candidates where the proposed new use has:

1. Compelling evidence of effectiveness,
2. Same dosage form/route as an approved indication, and
3. Comparable safety profile between the new-use population and labeled populations.
   FDA also invites candidates not meeting all criteria if there are preliminary promising data addressing unmet need.

Requested inputs:

1. Priority areas: FDA’s initial chronic disease priorities are metabolic diseases, neurodegenerative conditions, women’s health (e.g., menopause), men’s health (e.g., testosterone deficiency), substance use disorders, and rare diseases; asks whether to agree and what else to include.
2. Candidate drugs, organized into three evidence scenarios:
   • Scenario 1: sufficient existing evidence to support safety/efficacy for a new use (no new trials needed; may rely on public literature and/or completed adequate/well-controlled investigations). FDA reiterates the “substantial evidence” standard and that in some cases one adequate and well-controlled study with confirmatory evidence may suffice.
   • Scenario 2: preliminary clinical signals (case reports/pilot studies) but not enough for labeling; seeks candidates meriting further study.
   • Scenario 3: preclinical signals only (e.g., screening, in vitro, AI/ML), no clinical evidence yet.
3. Methods to identify candidates: FDA requests innovative approachesit could use to facilitate candidate identification.
4. Barriers/opportunities:
   • barriers when no commercial interest exists for a supplemental filing,
   • barriers for patients/clinicians using approved drugs for unapproved uses even when medically appropriate,
   • what FDA/federal partners could do to address barriers,
   • how FDA/federal partners can collect/use data (including real-world data) on unapproved uses to understand community practice.

 FDA is particularly focused on new uses to treat chronic or rare diseases and announced it is soliciting input on efforts with respect to drug repurposing to help address unmet medical needs across a range of diseases and conditions.