FDA Calls for Input on Repurposing Approved Drugs for Unmet Medical Needs

The FDA has announced that it is formally requesting public input to identify approved drugs that could be repurposed for new indications, particularly in rare diseases, metabolic conditions, and other areas where treatment options remain inadequate and commercial incentives to pursue new approvals are limited.¹ Comments are due June 11, 2026, under docket number FDA-2026-N-4492.

The initiative is part of a broader FDA effort to update labeling for approved drugs when scientific evidence supports new uses. Rather than waiting for industry to file supplemental applications, the agency is proactively asking clinicians, researchers, patients, and other stakeholders to flag candidates for which existing data from case reports, observational studies, or even preclinical findings could justify a new indication or patient population.

"Too many patients lack effective treatment options, even when promising science exists," FDA Commissioner Marty Makary, MD, MPH, said in a news release. "Drug repurposing can make better use of available scientific data to deliver effective treatment options for patients in need."

The FDA is specifically requesting nominations for drugs for which sufficient evidence may already support a new use, as well as those with promising preliminary clinical data warranting further study and preclinical signals, including findings from artificial intelligence (AI) and machine learning tools that could point to repurposing opportunities.

The agency is also seeking input on structural barriers that prevent repurposed drugs from reaching patients, including the lack of financial incentives for manufacturers to pursue label changes supported by publicly available science.

Targeting the Gaps AI Is Already Exposing

The FDA's initiative, which explicitly calls for nominations based on emerging AI and machine learning data, aligns with growing recognition that AI is fundamentally expanding what drug repurposing can look like in practice.

In an interview with The American Journal of Managed Care^® (AJMC^®) during the 2025 Patient-Centered Oncology Care® conference, Vivek Subbiah, MD, chief of early phase drug development at Sarah Cannon Research Institute in Nashville, Tennessee, described how AI is reshaping both clinical trial access and the discovery of repurposing candidates.²

"What we used to think about is actionable vs nonactionable," Subbiah said. "With AI, we are discovering the nonactionable genes as actionable because AI is coming up with new pathways."

He added that AI-based algorithms can identify subsets of patients who responded to drugs that failed in broader trials. "These are not failed drugs; these are failed trials," Subbiah said.

Rare Disease Applications: Matching the Right Hammer to the Nail

The FDA's particular interest in rare diseases reflects a well-documented gap in dermatology and other specialty fields.¹ In an interview with AJMC, Cory Simpson, MD, PhD, assistant professor of dermatology at the University of Washington in Seattle, noted that although targeted therapies have transformed care for common inflammatory diseases such as atopic dermatitis (AD) and psoriasis, patients with rare genetic conditions such as epidermolysis bullosa simplex have seen far less progress.³

He described the promise of repurposing as finding shared molecular pathways between well-characterized diseases and rare disorders. Simpson gave the example of asking whether dupilumab, which addresses itch in AD, could meaningfully relieve symptoms in a blistering disease through a similar mechanism.

"Let's find out more about the nail so we know which hammer to use," he said.

Guiding Collaborations and Action

The FDA has indicated it will use input from the docket to refine its repurposing evaluation framework and to guide collaborations with the National Institutes of Health (NIH) and CMS.¹ The initiative builds on existing programs, including Project Renewal, which has already updated labeling for several oncology drugs to reflect current science. It is also consistent with a September 2025 federal directive instructing the FDA and NIH to jointly investigate repurposing opportunities for the treatment of patients with chronic diseases.

For clinicians, this is a rare formal opening to push evidence-backed repurposing ideas into a federal review process, particularly for patient populations that rarely attract pharmaceutical investment.

References

1. FDA advances drug repurposing to address unmet medical needs. News release. FDA. May 11, 2026. Accessed May 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-advances-drug-repurposing-address-unmet-medical-needs
2. McCormick B, Subbiah V. AI expands clinical trial access, advances drug repurposing efforts. AJMC. October 8, 2025. Accessed May 12, 2026. https://www.ajmc.com/view/ai-expands-clinical-trial-access-advances-drug-repurposing-efforts-vivek-subbiah-md
3. Simpson C, Hebebrand M, McNulty R. The potential of drug repurposing for inherited dermatologic diseases. AJMC. July 26, 2025. Accessed May 12, 2026. https://www.ajmc.com/view/the-potential-of-drug-repurposing-for-inherited-dermatologic-diseases-cory-simpson-md-phd