FDA Seeks Ideas for Repurposing Drugs to Address Unmet Needs

Rare Daily Staff

The U.S. Food and Drug Administration is turning to drug repurposing as a new lever in its push to close long-standing treatment gaps for people living with rare diseases, inviting patients and researchers to help identify promising, overlooked therapies.

In a new request for information, the FDA said it is seeking concrete ideas for new uses of already approved medicines in areas of “significant unmet medical need,” explicitly naming rare diseases alongside metabolic and neurodegenerative conditions, women’s and men’s health, and substance use disorders.

Officials emphasized that many of these conditions lack any FDA-approved therapy or have only one option that may not work for all patients, making repurposing a particularly attractive strategy.

“Too many patients lack effective treatment options, even when promising science exists,” FDA Commissioner Marty Makary said in the announcement, framing repurposing as a way to translate existing data into real-world benefit for underserved patient groups.

The agency is asking patients, clinicians, investigators, and other stakeholders to flag drugs with evidence that could support a new indication or population, including small, uncontrolled rare-disease studies that would typically struggle to attract commercial backing. The agency is especially interested in cases where there is plausible scientific support for a new rare-disease use but “limited commercial incentives” to pursue a supplemental approval — a common barrier when the underlying drug is generic or the target population is extremely small.

Submissions can include three types of candidates: drugs with evidence that may already justify a labeling change; drugs supported by preliminary clinical experience, such as case series or observational data; and drugs with preclinical or in silico signals, including hits from artificial intelligence and machine learning platforms.

The initiative dovetails with a broader modernization push at the FDA to make labeling more reflective of current science, including for small-population conditions. It builds on authorities such as the Best Pharmaceuticals for Children Act and the MODERN Labeling Act, as well as the FDA’s Project Renewal, which has already updated labels for several oncology drugs based on newer data that often include rare cancer subtypes.

It also aligns with the Trump administration’s 2025 “Make Our Children Healthy Again” strategy, which directed the FDA and the National Institutes of Health to strengthen the use of repurposed drugs for chronic disease and to rely more on collaborative trial designs to support approvals — a framework that rare-disease researchers say could be adapted to ultra-small patient populations.

In parallel, the FDA has rolled out rare-disease–specific efforts such as the Accelerating Rare Disease Cures (ARC) program and new evidence principles designed to bring more predictability to how the agency weighs nontraditional data streams in small populations.

The FDA is asking the rare-disease community to move beyond general commentary and submit disease-specific and drug-specific proposals, along with supporting data. Examples could include long-term registry data showing benefit from an off-label therapy, mechanistic rationale paired with early case reports, or AI-derived signals pointing to an existing drug that modulates a pathway known to drive a particular rare disorder.

The agency is also seeking feedback on systemic barriers that keep repurposed drugs from reaching rare-disease patients, such as a lack of financial incentives for label changes, data fragmentation across small centers, and challenges in designing traditional randomized trials in ultra-rare conditions.

The FDA says the input will inform how it refines its approach to evaluating and facilitating repurposing opportunities, including future collaborations with the NIH and the Centers for Medicare & Medicaid Services that could shape evidence requirements and coverage decisions for repurposed therapies.

Photo: FDA Commissioner Marty Makary