Drug repurposing: Stakeholders say FDA should act within its authority, avoid disincentives
Patient and healthcare industry stakeholders told the US Food and Drug Administration (FDA) that while there are significant opportunities to repurpose existing drugs, the agency should ensure any new framework for repurposing drugs does not disincentivize investment or competition and fits within agency’s existing statutory authority.
In May, FDA opened a public docket to get feedback on how it can promote repurposing drugs for unmet medical needs, specifically for drugs where manufacturers have no commercial interest in adding a new use through a supplemental application. Since issuing the request for information, the agency has received more than 600 comments, including comments from patient advocacy groups and healthcare product lobby groups.
Existing authorities
The National Organization for Rare Diseases (NORD) wrote to FDA and noted that numerous private and public efforts are underway to systematically evaluate the potential repurposing of drugs for new treatments to address unmet needs, including the use of artificial intelligence and other computing technologies. However, it added that finding repurposed uses for drugs becomes more complicated when additional clinical trials are required.
The group said that when making recommendations for repurposing drug trials, the agency should rely on its existing tools and authorities, including external controls, biomarkers, adaptive trial designs, and real-world evidence.
NORD emphasized that the FDA should independently review broadly available scientific information to determine whether a new indication can be added to a repurposed drug, consider the use of patient-reported outcomes, and collaborate with other agencies such as the National Institutes of Health and the Advanced Research Projects Agency for Health. The group also said the agency should ensure it has access to the underlying data when it is provided by a third party and encouraged reviewers to prioritize unmet needs in its review process.
"Repurposing drugs in the rare disease space leads to unique challenges and opportunities," said NORD. "Drug repurposing is uniquely suited to rely on real-world evidence (RWE), because some drugs are used off-label in clinical settings and provide real data on drug safety and efficacy.
"FDA must issue guidance on how real-world data may be used to support approvals and expansions to drug labels for rare diseases," the group added. "Because so few rare diseases have FDA-approved therapies, patients may already be receiving treatment off-label, making recruiting for a prospective clinical trial nearly impossible."
NORD added that FDA should explore policies and incentives that make it feasible to generate evidence for repurposing drugs and all stakeholders should look for opportunities to collaborate to help bring such drugs to market.
Competition and incentives
The Association for Accessible Medicines (AAM) wrote to FDA, stating that while repurposing drugs may be a more efficient way to leverage prior information, regulators should preserve the well-established statutory and regulatory frameworks for generic drugs and biosimilars. The group said the agency should not create uncertainty regarding labeling obligations, intellectual property protections, or approval standards in the pursuit of finding new uses for old drugs and cautioned that the agency's actions may inadvertently be detrimental to patient access.
"FDA should ensure that any repurposing initiative remains consistent with the balance established by the Hatch-Waxman Act and the Biologics Price Competition and Innovation Act," said AAM. "Repurposing efforts should not inadvertently alter existing patent or exclusivity incentives, nor should they create uncertainty regarding labeling carve-outs, or other established pathways that facilitate timely patient access to lower-cost generic medicines.
"Maintaining predictable incentives for both innovation and competition remains critical to a sustainable generic and biosimilar pharmaceutical marketplace," the group added.
The US Chamber of Commerce also raised concerns about how FDA's efforts could affect intellectual property protections. The groups said they want to ensure the innovation ecosystem can be calibrated to support investments in repurposing research and isn't negatively affected, leading to a dearth of investment.
"Drug repurposing research — particularly for new indications of off-patent or generic compounds — presents a unique commercial challenge: the underlying molecule may be freely available, yet the cost of clinical development to establish a new use may be substantial, depending on the additional evidentiary burden required beyond existing data supporting the repurposed indication," said the Chamber. "Without robust intellectual property (IP) protections to reward that investment, sponsors have limited financial incentive to pursue FDA approval for repurposed applications, even where scientific evidence is promising.
"The Chamber supports a flexible, case-by-case approach to evidentiary expectations, paired with clear FDA guidance (as described in Section II) and recommends that IP protections and exclusivity incentives be calibrated to the level of investment each candidate requires," the group added.
More specifically, the Chamber asked FDA to work with Congress and other stakeholders to ensure orphan drug exclusivity, three-year exclusivity for new indications, the patent term extensions (PTEs) under Hatch-Waxman, and method-of-use patents are appropriately calibrated to ensure the incentive systems are not hampered by any new framework for repurposing drugs. The group also asked the agency to establish clear guardrails on who qualifies to submit a drug repurposing application.
Maintaining standards
AAM said that FDA should consider the potential impact of its actions on generic drug labeling and manufacturer responsibilities in the postmarket setting. Echoing other stakeholders, the group emphasized that the agency should maintain its evidence-based, risk-proportionate standards and noted that RWE and real-world data may provide historical evidence to justify drug repurposing.
"High-quality RWE may provide meaningful information regarding treatment effectiveness, safety, utilization patterns, and outcomes in broader patient populations that may not be adequately represented in traditional clinical trials," said AAM. "Leveraging existing healthcare data may also reduce development costs, improve the feasibility of generating evidence for products that would otherwise be unlikely to attract investment in additional development programs, and accelerate patient access to beneficial therapies.
"FDA should clearly communicate the evidentiary expectations that would support any labeling change to ensure the change meets the current standards for approval and are based on sound science to ensure consistency and stakeholder confidence in regulatory decision-making," the group added.
Public-private partnerships
AAM echoed NORD's support for partnering with public and private stakeholders. The group went a step further and encouraged the agency to consider creating a public-private framework to identify drug repurposing opportunities.
"We support FDA’s efforts to collaborate with other federal agencies, academic institutions, healthcare systems, patient organizations, and industry stakeholders to identify promising repurposing candidates," said AAM. "Existing federal healthcare datasets and evidence-generation platforms may provide valuable opportunities to identify potential new uses supported by real-world clinical experience.
"Such a collaborative approach could help maximize public health benefits while ensuring that candidate selection and evaluation remain grounded in sound science," the group added.
AAM also asked FDA to be transparent as it moves forward, especially regarding factors such as selection criteria, evidentiary expectations, decision-making processes, and implementation considerations.
The Chamber of Commerce also encouraged coordination to develop a framework for repurposing drugs, especially across federal agencies such as NIH, the Centers for Medicare and Medicaid Services, and the Department of Veterans Affairs. It recommended creating a formal interagency working group to address the topic, working with CMS to address coverage and reimbursement issues, and engaging with global regulators.
"The Chamber emphasizes that such interagency coordination should be limited to aligning regulatory and coverage pathways and should not extend to price, cost, or market conditions as considerations of FDA’s approval decisions," said the Chamber. "FDA’s approval standard must remain grounded solely in the statutory criteria of safety and substantial evidence of effectiveness, and coordination across agencies should in no way introduce pricing or market-based factors into that determination."
Duke-Margolis
The Duke-Margolis Center for Health Policy noted that it has convened stakeholder for a private expert roundtable on drug repurposing in November 2024, followed by a public workshop on the topic in May 2025. It submitted a report to FDA on its findings from those meetings.
"Nontraditional developers, such as nonprofits, patient organizations, and academic institutions, see the value of generic drug repurposing for patients and are the most active in pursuing these opportunities," said Duke-Margolis. "However, the current regulatory system is designed primarily for industry sponsors, leaving nontraditional developers without a clear path to pursuing regulatory approval for new uses of generic drugs, which can have a detrimental impact on patient access.
"The FDA and other agencies across the Department of Health and Human Services have an opportunity to support these nontraditional developers and ensure drug labels are updated to promote public health," the center added.
Among its recommendations, Duke-Margolis said the agency should enhance and leverage existing programs. While experts recommended creating a new drug repurposing support program that would provide sponsors with advice on issues such as research protocols and evidentiary needs, the center said FDA already provides such support through mechanisms, including guidances and workshops.
"Expanding these efforts to drug repurposing and providing specific educational materials and regulatory advice could help support the nontraditional developers who typically lead repurposing efforts and may lack the experience of navigating regulatory approval," said Duke-Margolis. "Such efforts would be similar to other FDA programs to support patient advocacy organizations and small business initiatives."
One such effort that experts said should be expanded is CURE ID; a collaboration between FDA, the National Center for Advancing Translational Sciences (NCATS), the World Health Organization (WHO), and the Critical Path Institute. The collaboration provides a platform for health care providers, patients, and caregivers to share treatment experiences with existing drugs used off label.
Duke-Margolis discussed using other mechanisms under FDA's current authority, including using citizen petitions and federal register notices to evaluate new uses for existing drugs and allow their use.
"This approach was recently used to expand the use of buprenorphine; although, the expansion was only for a dosage change rather than a new indication," said the center. "The idea of using Citizen Petitions and FRNs offers an alternative to other policy recommendations, such as the Expansion of Project Renewal or Utilizing the Modern Labeling Act, both of which give FDA the authority to make label updates but place the burden on the agency to identify opportunities and data."
Duke-Margolis also presented solutions that would require large-scale policy solutions, such as creating a new regulatory pathway for non-traditional developers to seek a label change.
