Description

Overview of the Challenge

The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) has developed the Repurposing Generic (ReGen) Drugs program, a multi-step program to 1) help identify generic drug repurposing opportunities, 2) build the evidence needed to support their use, and 3) expand access to affordable treatments for diseases that place a high burden on the healthcare ecosystem. This challenge is part of the first step of the program and is intended to bring to light potential treatments that are not well-known for costly conditions.

Through this Evidence Package Challenge, NIH is soliciting evidence-based generic drug repurposing opportunities for high-cost conditions. Packages that identify generic drug repurposing opportunities where there is, at minimum, a clinical signal of efficacy as evidenced through computational and data-driven studies, observational studies, a phase 2 clinical trial or based on analysis of real-world data (RWD) will be accepted for judging. Clinical signals based solely on an individual’s or a single institution’s experience will not be accepted for judging. Prizes will be awarded based on the strength of clinical evidence. The total prize purse is up to $4,000,000. Up to 40 prizes will be awarded. Each prize will be $100,000.

The evidence packages should consist of a thorough review of the safety and effectiveness data and information supporting the repurposing hypothesis for a given drug-disease pair. It is also acceptable if there are gaps in a package if the evidence is not available; however, to qualify for judging, the package must contain clinical evidence of efficacy beyond a case report or the experience of a single institution.

The submissions received may be used to inform future opportunities to generate evidence leading to addition of the new use to FDA-approved labeling and/or addition to compendia to support coverage of those treatments and adoption in clinical practice.

Subject of the Challenge

National healthcare expenditure is increasing at a concerning rate, and while among listed FDA-approved drugs there are more than 32,000 generic drugs and more than 1,300 active ingredients, there is little incentive for the pharmaceutical industry to invest in studies to support the addition of a new indication to a marketed drug when there are generic forms of the drug available. As a result, drugs with generic competitors remain a largely unexplored resource for treating more diseases or conditions. This is despite the fact that repurposing low-cost drugs that have no unexpired patents or exclusivity offer a promising opportunity to help accelerate access to effective treatments, improve health outcomes, and reduce healthcare expenditure. This tension between the promise of repurposing drugs with no patents or exclusivity and the economic barriers limiting their development has long been recognized and serves as a key consideration for this prize competition.

In 2019, the NIH/NCATS, FDA, and the Reagan-Udall Foundation hosted a workshop “Repurposing Off-Patent Drugs: Research and Regulatory Challenges” that addressed challenges of repurposing off-patent drugs, which include there being few regulatory pathway options, non-existent financial incentives for drug developers, and a lack of clear ownership to address the gaps, even though repurposing generic drugs would be an efficient drug development strategy compared to development of a new drug.[1]

In May 2025, the Duke Margolis Institute hosted a workshop “Generic Drug Repurposing: Exploring the Potential Role of the Regulator and Policy Solutions,” and discussed limitations of current regulatory pathways for generic drug repurposing and suggested possible regulatory and legislative solutions. The discussion emphasized coordinated actions across the whole biomedical system, with regulators like the FDA playing a key role in updating outdated drug labels using existing authorities and the evidence required. One pathway suggested was to leverage the FDA citizen petition process through which the public could submit evidence of safety and effectiveness of the new use, and as suggested by meeting participants could then be used by FDA to post a Federal Register Notice of their findings with a draft of the updated label.[2]

The Make Our Children Healthy Again Strategy Report, released on September 9, 2025,[3] outlines 120 actions to address the rise of chronic disease in the United States, and one such action focuses on drug repurposing: “Repurposed Drugs: The NIH and FDA will jointly investigate opportunities to strengthen the use of repurposed drugs for the treatment of chronic disease, while harmonizing authorization processes through collaborative clinical trial designs to achieve FDA approval.”

And most recently, on August 5, 2026, the Reagan-Udall Foundation held a public hybrid meeting, “Drug Repurposing: Considerations for Selection Criteria and Prioritization,” where representatives from several DHHS agencies, clinicians, researchers, and patients shared their perspectives and approaches for identifying new uses for approved drugs.

In response, the National Institutes of Health (NIH), led by the National Center for Advancing Translational Sciences (NCATS) and supported by the NIH Bio Genesis Program announces the ReGen Drugs Evidence Package Challenge to identify promising generic drug candidates that could be repurposed to treat high-cost conditions. The submissions received may be used to inform future opportunities to generate evidence leading to updating FDA-approved labeling with the new uses and/or addition to compendia to support coverage of those treatments and adoption in clinical practice.

The goal of this Challenge is to identify evidence-based, generic drug-disease pairs and prioritize drug repurposing opportunities for high-cost conditions worth testing in clinical trials or those drug disease pairs demonstrating substantial evidence of effectiveness that the FDA-approved labeling or compendia could be updated based on existing evidence from clinical studies, real-world evidence, and other sources to support regulatory approval and clinical adoption. The focus on conditions that are costly to the healthcare system is because the expanded ReGen Drugs program will establish a model that leverages the savings that are realized by the healthcare system as a result of treating costly conditions with generic drugs. Some of those savings can be directed to treatments for other patients and some of the savings can be used to support more generic drug repurposing. In order to realize enough savings to have that impact, the starting point needs to be conditions that are costly to the healthcare system.

This Challenge Focuses on the Following Priority Conditions

• Alzheimer’s disease and related dementias
• Cancer and cancer related conditions
• Chronic kidney disease
• Common cardiovascular diseases
• Common mental health conditions
• Common neurologic conditions
• Diabetes
• Osteoarthritis
• Substance use disorders, including alcohol

Conditions not listed above may be considered but the participant must provide citations for the costs to the healthcare system.

To Be Competitive

The drug to be repurposed must have no unexpired patents or exclusivity.

In addition, the following are of highest priority for this challenge:

• Drugs addressing a priority condition (above)
• Drug to be used for a disease in a completely different class than the disease on the label (for example, a chemotherapy to be repurposed for a condition outside of oncology, or vice versa)
• Drugs not commonly prescribed off label for the new indication
• New indication stems from RWD/RWE but is not currently prescribed for the new indication

Attributes of low priority evidence packages would be:

• New indication is the same disease class/type as the approved indication – for example, proposing the use of a chemotherapy approved for one cancer to treat another type of cancer, or a psychiatric drug to be repurposed for a closely related psychiatric condition
• Conditions that are not costly to the healthcare system (over $1B annually)
• Submissions for drugs commonly used off-label for the indication that are solely based on an individual’s or an institution’s experience and do not present systematic analysis of real-world data, or a clinical trial.
• Repurposing that would require a new formulation of the drug
• Packages that do not present a signal of clinical efficacy

Low priority packages will not be eligible for a prize and will not be accepted.

Partners: NCATS is conducting this Challenge with support from the NIH Chief Artificial Intelligence Officer within the Division of Program Coordination, Planning, and Strategic Initiatives of the NIH Office of the Director.

Statutory Authority to Conduct the Challenge

The NIH National Center for Advancing Translational Sciences (NCATS) is conducting this Challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, as amended [15 U.S.C. § 3719]. NCATS’ mission is to turn research observations into health solutions through translational science. This Challenge is consistent with and promotes NCATS’ mission to turn research observations into health solutions through translational science.

Dates

• Challenge launch: September 8, 2026
• Registration open: November 2, 2026
• Registration deadline: January 15, 2027
• Evidence package submissions due: March 26, 2027
• Review completed: June 3, 2027
• Winners announced: July 2, 2027

Prizes

Amount of the Prize

The total prize purse for the ReGen Drugs Evidence Package Challenge is up to $4,000,000. Up to 40 prizes will be awarded. Each prize will be $100,000. Prizes will be awarded for evidence packages based on the strength of clinical evidence where there is at minimum, a clinical signal of efficacy as evidenced through observational studies, a phase 2 clinical trial, or based on analysis of real-world data (RWD), for example. Clinical signals based solely on an individual’s or a single institution’s experience will not be accepted for judging.

Any decision to increase individual prize amounts from what is outlined above is entirely at the discretion of the NIH/NCATS.

Please note, in addition to the quality of the evidence packages, NCATS/NIH will strive to award prizes across a variety of diseases and conditions.

Award Approving Official

The Award Approving Official will be the Director of the National Center for Advancing Translational Sciences, or as otherwise delegated.

Payment of the Prize

Prizes awarded under this Challenge will be paid by electronic funds transfer and may be subject to federal income taxes. The Department of Health and Human Services (HHS)/NIH will comply with the Internal Revenue Service withholding and reporting requirements, where applicable. Entities participating in this Challenge are encouraged, but not required, to request and obtain a free Unique Entity ID (UEI), if they have not already done so, via SAM.gov as this will expedite prize payment. Additional information can be found at https://sam.gov/content/entity-registration.

NIH/NCATS reserves the right, in its sole discretion, to (a) cancel, suspend, or modify the Challenge, or any part of it, for any reason, and/or (b) not award any prizes if no submissions are deemed worthy.

Rules

Eligibility Rules

To be eligible to win a prize under this Challenge, a Participant (whether participating as an Individual, a Team, or an Entity):

1. Shall have registered to participate in the Challenge under the rules promulgated by the National Institutes of Health (NIH) as published in this announcement;
2. Shall have complied with all the requirements set forth in this announcement;
3. In the case of a private entity, shall be incorporated in and maintain a primary place of business in the United States, and in the case of an individual, whether participating singly or in a group, shall be a citizen or permanent resident of the United States. However, non-U.S. citizens and non-permanent residents can participate as a member of a team that otherwise satisfies the eligibility criteria. Non-U.S. citizens and non-permanent residents are not eligible to win a monetary prize (in whole or in part). Their participation as part of a winning team, if applicable, may be recognized when the results are announced.
4. Shall not be a federal entity or federal employee acting within the scope of their employment;
5. Shall not be an employee of the Department of Health and Human Services (HHS, or any other component of HHS) acting in their personal capacity;
6. Who is employed by a federal agency or entity other than HHS (or any component of HHS), should consult with an agency ethics official to determine whether the federal ethics rules will limit or prohibit the acceptance of a prize under this Challenge;
7. Shall not be a judge of the Challenge, or any other party involved with the design, production, execution, or distribution of the Challenge or the immediate family of such a party (i.e., spouse, parent, step-parent, child, or step-child).
8. Shall be 18 years of age or older at the time of submission.

Participation Rules

(1) Federal grantees and recipients of cooperative agreements or other transaction (OT) awards are eligible to participate in the Challenge but may not use Federal funds from a grant award, cooperative agreement, or OT award to develop their Challenge submission or to fund efforts in support of their Challenge submission unless use of such funds is consistent with the purpose, terms, and conditions of the grant award, cooperative agreement, or OT award. Each Participant (whether participating as a Team or an Entity) intending to use Federal grant, cooperative agreement, or OT award funds must register for and participate in the Challenge as an entity on behalf of the awardee institution, organization, or entity. If a winning Participant uses Federal grant, cooperative agreement, or OT award funds to participate in the Challenge, the prize must be treated as program income for purposes of the original grant, cooperative agreement, or OT award in accordance with applicable Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards [2 CFR § 200]. Participants using Federal grant, cooperative agreement, or OT award funds to participate and/or report prize funding as program income (for winning Participants) should coordinate with the awarding official at the federal awarding agency.

(2) Federal contractors may not use federal funds from a contract to develop their Challenge submissions or to fund efforts in support of their Challenge submissions.

(3) By participating in this Challenge, each Participant (whether participating as an Individual, a Team, or an Entity) agrees to assume any and all risks and waive claims against the federal government and its related entities, except in the case of willful misconduct, for any injury, death, damage, or loss of property, revenue, or profits, whether direct, indirect, or consequential, arising from participation in this Challenge, whether the injury, death, damage, or loss arises through negligence or otherwise.

(4) Based on the subject matter of the Challenge, the type of work that it will possibly require, as well as an analysis of the likelihood of any claims for death, bodily injury, property damage, or loss potentially resulting from Challenge participation, no Participant (whether participating as an Individual, a Team, or an Entity) participating in the Challenge is required to obtain liability insurance, or demonstrate financial responsibility, or agree to indemnify the federal government against third party claims for damages arising from or related to Challenge activities in order to participate in this Challenge.

 

(5) A Participant (whether participating as an Individual, a Team, or an Entity) shall not be deemed ineligible because the Participant used federal facilities or consulted with federal employees during the Challenge if the facilities and employees are made available to all Participants participating in the Challenge on an equitable basis.

(6) By participating in this Challenge, each Participant (whether participating as an Individual, a Team, or an Entity) warrants that they are sole author or owner of, or has the right to use, any copyrightable works that the submission comprises, that the works are wholly original with the Participant (or is an improved version of an existing work that the Participant has sufficient rights to use and improve), and that the submission does not infringe any copyright or any other rights of any third party of which the Participant is aware.

(7) By participating in this Challenge, each Participant (whether participating as an Individual, a Team, or an Entity) grants to the NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share, and display publicly the submission on the web or elsewhere, and agrees to grant a nonexclusive, nontransferable, irrevocable, paid-up license to practice, or have practiced for or on its behalf, the solution throughout the world for non-commercial educational or research purposes. Each Participant will retain all other intellectual property (IP) rights in their submissions, as applicable. To participate in the Challenge, each Participant must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of the Participant’s rights to the federal government. To receive an award, Participants will not be required to transfer their intellectual property rights to NIH, but Participants must grant to the federal government the nonexclusive licenses recited herein.

(8) Each Participant (whether participating as an Individual, a Team, or an Entity) agrees to follow all applicable federal, state, and local laws, regulations, and policies.

(9) Each Participant (whether participating as an Individual, a Team, or an Entity) participating in this Challenge must comply with all terms and conditions of these rules, and participation in this Challenge constitutes each such Participant’s full and unconditional agreement to abide by these rules. Winning is contingent upon fulfilling all requirements herein.

(10) As a condition for winning a cash prize in this Challenge, each Participant (whether participating as an Individual, a Team, or an Entity) that has been selected as a winner must complete and submit all requested winner verification and payment documents to NIH within 10 business days of formal notification. Failure to return all required verification documents by the date specified in the notification may be a basis for disqualification of a cash prize winning submission.

Judging Criteria

Basis Upon Which a Winner Will be Selected. This prize competition is intended to bring to light potential treatments that are not well known for costly conditions. Prizes will be awarded based on the strength of clinical evidence where there is at minimum, a clinical signal of efficacy as evidenced through a phase 2 clinical trial or based on analysis of real-world data (RWD). Clinical signals based solely on an individual’s or a single institution’s experience will not be accepted for judging. Gaps in the evidence package are acceptable if the data are not available. Gaps should be noted in the assessment.

Please note that published data generated by a participant team member should be clearly indicated (e.g., the addition of an asterisk with the specific reference numbers embedded in the text) in the package and will be given more weight than the same data cited by a different participant. However, these data are considered in the evidence package as a whole.

Submissions to this Challenge will be evaluated using the following criteria:

Rationale and Risk/Benefit

How strong is the evidence for the proposed mechanism of action of the drug and the role of the drug’s target in the new indication? How well-aligned is the risk/benefit balance for the indication proposed?

Non-clinical Evidence

Does the submission indicate sufficient non-clinical evidence that the drug is safe and effective in preventing or treating the new indication is provided? Does the evidence support the dosage and duration of the new use in the new population?

Safety

How well does the evidence demonstrate safety for the new indication? Does the evidence support the dosage and duration of the new use in the new population?

Clinical and Real-world Evidence

How strong is the clinical and/or real-world evidence (i.e., publications, clinical trials or other systematic study, summarized data, statistical analyses) and that the drug is effective in preventing or treating the new indication? Is the apparent impact on the new indication clinically meaningful (prevents, postpones, treats, etc.)?

Pharmacogenomics

How strong is the pharmacogenomic or other evidence provided, if any, to support efficacy in a subpopulation of patients?

Treatment Regimen

To what extent were considerations presented for use of the current formulation(s) of the drug and treatment regimen of the drug for the new indication? Are there any concerns that the new patient population would have problems tolerating or adhering to the formulation or regimen proposed?

Assess the information provided regarding drug-drug interactions for commonly used drugs in the population for the new indication.

Additional Considerations

Which evidence in the package was generated by the participant, if any? How much does that evidence contribute to the package as whole? In its absence would the strength of the package be diminished?

How to Enter

Registration Process: The official announcement for the ReGen Drugs Evidence Package Challenge is available at www.nih.gov/challenges. Further information about the Challenge registration and submission portal will be provided closer to the submission start date.

To register, Participants will first be directed to establish an account in the submission portal (details will be provided closer to the submission start date). Participants will be required to identify whether they are registering as either of the following: as an individual, an independent Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation) or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). Participants will need to provide the name, affiliation, and contact information of all individuals competing in this Challenge as part of a Team or on behalf of an Entity. Participants will need to provide the drug and corresponding indication for which the evidence package will be submitted. All Participants will also be required to acknowledge whether federal funding will be used in the development of the Challenge submission (see Participation Rule 1). All Participants must certify they have read, understand, and agree to abide by the official eligibility rules, participation rules, and requirements for the Challenge as stated in this announcement.

• For Individuals: To be eligible to receive a cash prize, the Individual must be a citizen or permanent resident of the United States.
• For Teams: Each participating Team is required to identify a Team Captain who will register and submit on behalf of the Team members. The Team Captain is responsible for all communications with the Challenge sponsors and, in the event of winning a cash prize, will be paid the prize in full. To be eligible to receive a cash prize, the Team Captain must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Captain who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible.
• For Entities: Each participating Entity is required to identify a Point of Contact who will register and submit on behalf of the Entity. The Point of Contact is responsible for all communications with the Challenge sponsors. In the event of winning a cash prize, the prize will be paid directly to the Entity, not to the Point of Contact. To be eligible to receive a cash prize, the Entity must be incorporated in and maintain a primary place of business in the United States. As stated in the Participation Rules, Participants intending to use Federal grant, cooperative agreement, or OT funds must register for and participate in the Challenge as an Entity on behalf of the awardee institution or organization. In the event that a dispute regarding the identity of the Point of Contact who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible.

Participants must complete all required registration steps within the submission portal in advance of the Registration Deadline of November 2, 2026.

Submission Requirements

It is understood that the evidence submitted in this package will largely be drawn from public sources and not from the participant’s own work. The content should identify references and sources throughout just as would be done for a review article. Anything submitted that is the participant’s own work whether published or not, should also be clearly indicated (for example, with asterisks) as that data will be given more weight than the same data cited by a different participant. However, those data are considered in the evidence package as a whole.

To the extent possible, the evidence package content should include:

Overview (one page):

• Drug
• Generic forms of the drug. This does not need to be comprehensive, but will help in assessing whether generic forms are already on the market or if the drug is just off-patent and off-exclusivity.
• Labeled indication(s) and dosing information. This does not need to be comprehensive, but helps assess how close the new indication is to the already approved indication(s).
• What, if any, contraindications are listed for this drug?
• What warnings are included on the label?
• What is the new indication being proposed?
• How does the new indication population differ from the population(s) described in the U.S. Prescribing information (USPI) for this drug?
• What is the dosage form and regimen proposed for the new indication (if understood)?

Evidence Package Content (page limit: 14 pages):

For each section, please include the letter and title (listed below) at the top of the section of the evidence package.

1. Rationale. Provide a brief statement identifying the pharmacologic class of the drug (the current FDA approved indication(s)), the FDA-approved formulation proposed herein and a discussion of the scientific rationale for the drug, its intended use, and the potential clinical benefits of the drug product. If the condition is not on the priority list above, provide citations for the costs to the healthcare system.
2. Risk/Benefit. Please describe the benefit and risk considerations related to the drug, including a discussion of any additional studies (safety or efficacy) that would be needed to make a compelling case for the new use.
3. Non-clinical evidence. Please provide data or description with citations (or indicate when data are unpublished) of the pharmacological actions of the drug in relation to its proposed new therapeutic indication.
4. Safety. To the best of your knowledge (including information provided in the drug label) please describe considerations regarding possible toxicological effects of the drug as they relate to the new clinical uses, including, as appropriate, studies assessing the drug’s acute, subacute, and chronic toxicity; carcinogenicity; and studies of toxicities related to the drug’s particular mode of administration or conditions of use. Please describe studies that otherwise define the existing pharmacologic properties (pharmacokinetics and pharmacodynamics) of the drug or are pertinent to possible adverse effects for the patient population of the new use.
5. Clinical and/or real-world data/evidence. Provide a description and analysis of clinical evidence pertinent to the proposed new use of the drug. In the case of controlled trials for the new use, include a description of the study design and pertinent inclusion/exclusion criteria that were used and statistical analyses used to evaluate the study. In the case of real-world data/evidence, provide the evidence source and provide information relevant to an evaluation of the safety and effectiveness of the drug for the new use in sufficient detail that the findings could be reproduced (evidence source, how data were collected, parameters of the analysis, etc.). If an AI tool was used, please provide the name of the tool and the parameters used.
6. Pharmacogenomic considerations. Please provide any pharmacogenomic or other patient stratification recommendations that would improve the efficacy or safety profile for the new use. Please describe any potential drug-drug interactions with other medications the new patient population may be using or medications the new use is intended to augment.
7. Treatment regimen. Is the new use for a stand-alone treatment or to be use as an adjunctive treatment? Describe the rationale for the dosage form and regimen for the new indication. Describe potential adherence concerns, if any, for the patient population of the new indication (tablet size, frequency or route of administration, etc.).
8. Additional considerations. Please use this section to provide any additional considerations including recommendations of clinical studies that may be needed before the drug is ready for regulatory approval, or addition to compendia.
9. References. Please provide sufficient information to allow the reader to find the source information. No specific format is required. References will not count toward the page limit.
10.  

IP Considerations

There is no expectation that a use patent has been or will be filed for the new indication. The presence of a use patent will have no bearing on the evaluation of the evidence package.

Additional Information

For Further Information Contact: [email protected]

Award Approving Official:

[1] https://sites.google.com/ncats.nih.gov/therapeutic-repurposing/off-patent-drug-repurposing/2019-research-regulatory-challenges-workshop

[2] https://healthpolicy.duke.edu/sites/default/files/2025-09/Regulatory%20Opportunities%20to%20Advance%20Generic%20Drug%20Repurposing.pdf

[3] https://www.hhs.gov/press-room/maha-commission-report-childhood-disease-strategy.html