Notice2026-09366
Drug Repurposing for Unmet Medical Needs; Request for Information
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Published
May 12, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is opening a public docket to solicit input and comments on FDA's efforts with respect to drug repurposing to address unmet medical needs. FDA is requesting information on potential priority disease areas and potential candidates for drug repurposing, with a focus on FDA-approved drugs for which there appears to be no commercial interest in adding a new use through a supplement to a new drug application (supplemental application). Information provided through this public docket will help the Agency refine our efforts toward considering and evaluating candidates for drug repurposing.
Full Text
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<title>Federal Register, Volume 91 Issue 91 (Tuesday, May 12, 2026)</title>
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[Federal Register Volume 91, Number 91 (Tuesday, May 12, 2026)]
[Notices]
[Pages 25897-25899]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-09366]
[[Page 25897]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-N-4492]
Drug Repurposing for Unmet Medical Needs; Request for Information
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for information; establishment of a public
docket.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
opening a public docket to solicit input and comments on FDA's efforts
with respect to drug repurposing to address unmet medical needs. FDA is
requesting information on potential priority disease areas and
potential candidates for drug repurposing, with a focus on FDA-approved
drugs for which there appears to be no commercial interest in adding a
new use through a supplement to a new drug application (supplemental
application). Information provided through this public docket will help
the Agency refine our efforts toward considering and evaluating
candidates for drug repurposing.
DATES: Submit either electronic or written comments, data, or
information by June 11, 2026.
ADDRESSES: You may submit comments, data, and information as follows.
Please note that late, untimely filed comments will not be considered.
The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept
comments until 11:59 p.m. Eastern Time at the end of June 11, 2026.
Comments received by mail/hand delivery/courier (for written/paper
submissions) will be considered timely if they are received on or
before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2026-N-4492 for ``Drug Repurposing for Unmet Medical Needs; Request
for Information.'' Received comments, those filed in a timely manner
(see ADDRESSES), will be placed in the docket and, except for those
submitted as ``Confidential Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Caroline Huang, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6117, Silver Spring, MD 20993-0002,
<a href="/cdn-cgi/l/email-protection#81e5f3f4e6f3e4f1f4f3f1eef2e8efe6c1e7e5e0afe9e9f2afe6eef7"><span class="__cf_email__" data-cfemail="7b1f090e1c091e0b0e090b140812151c3b1d1f1a55131308551c140d">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Drug repurposing refers to the identification of potential new uses
of FDA-approved drugs, for which the new uses would be supported by
safety and effectiveness data. Because drug repurposing takes into
account existing knowledge of approved drugs (e.g., safety profiles)
when considering the benefits and risks of potential new uses, it can
be an important approach for identifying potential treatments for
diseases, conditions, or populations that currently lack adequate
approved therapies. Stakeholder efforts to advance drug repurposing,
including workshops and white papers, have addressed topics such as
challenges and opportunities for drug repurposing and mechanisms
through which labeling could be updated when supported by sufficient
data.<SUP>1 2 3</SUP> Recognizing the potential public health impact of
drug repurposing, the September 2025 Make Our Children Healthy Again
strategy report directed FDA to jointly investigate opportunities with
the National Institutes of Health (NIH) 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.'' \4\
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\1\ <a href="https://videocast.nih.gov/watch/bb3e5157-d5db-11f0-9cf9-12c45c580ad9">https://videocast.nih.gov/watch/bb3e5157-d5db-11f0-9cf9-12c45c580ad9</a>.
\2\ <a href="https://healthpolicy.duke.edu/projects/drug-repurposing">https://healthpolicy.duke.edu/projects/drug-repurposing</a>.
\3\ <a href="https://remedi4all.org/international-drug-repurposing-conference/">https://remedi4all.org/international-drug-repurposing-conference/</a>.
\4\ <a href="https://www.whitehouse.gov/wp-content/uploads/2025/09/The-MAHA-Strategy-WH.pdf">https://www.whitehouse.gov/wp-content/uploads/2025/09/The-MAHA-Strategy-WH.pdf</a>.
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In many cases, applicants may consider drug repurposing and submit
a supplemental application under section 505(b) of the Federal Food,
Drug, and Cosmetic Act (FD&C Act) seeking approval of a new use. In
other cases where there are compelling data but potentially no
commercial interest in submitting a supplemental application under
section 505(b) of the FD&C Act (e.g., the brand drug has been
discontinued from marketing and only generic drugs are on the market;
the drug is marketed by the brand name applicant and/or generic drug
manufacturers but there appears to be insufficient commercial incentive
to pursue approval of a new use; etc.), FDA can use other complementary
approaches supported by existing legislation and regulatory pathways to
encourage labeling updates with new uses for drugs. Approaches such as
these have been successfully used in cases ranging from oncology drugs
to medical countermeasure drugs.
Existing legislation and regulatory mechanisms supporting labeling
updates. The Best Pharmaceuticals for Children's Act (BPCA, codified at
section 505A of the FD&C Act (21 U.S.C. 355a) and section 409I of the
PHS Act (42 U.S.C. 284m)) incentivizes the study of drugs for pediatric
indications when information relating to the use of those drugs in
children may produce pediatric health benefits, such as new uses of
drugs. Section 505A of the FD&C Act encourages the identification of
clinical areas of need in pediatric patients and offers exclusivity
appended to patent and exclusivity protection in certain circumstances
to applicants who, in response to a written request from the Agency,
submit data to the Agency to support new uses in pediatric patients.
Section 409I of the Public Health Service Act is implemented by NIH to,
among other things, identify and address drug products that need
further study in children.\5\
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\5\ <a href="https://www.nichd.nih.gov/research/supported/bpca/about">https://www.nichd.nih.gov/research/supported/bpca/about</a>.
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A second piece of legislation, signed into law as section 324 of
the Consolidated Appropriations Act of 2021 (Public Law 116-260),
``Modernizing the labeling of certain generic drugs'' (commonly
referred to as MODERN), added section 503D to the FD&C Act (21 U.S.C.
353d). This legislation established a process through which FDA can
require certain updates to the labeling of generic drugs when, among
other things, approval of the application for the generic drug's
reference listed drug (RLD) has been withdrawn for reasons other than
safety or effectiveness, and when there are no unexpired patents or
exclusivities listed in the FDA publication ``Approved Drug Products
With Therapeutic Equivalence Evaluations'' (commonly referred to as the
Orange Book) for the RLD. Under MODERN, FDA can initiate a process for
labeling changes if, among other things, updating the approved labeling
would benefit the public health and: ``(I) there is new scientific
evidence available pertaining to new or existing conditions of use that
is not reflected in the approved labeling; (II) the approved labeling
does not reflect current legal and regulatory requirements for content
or format; or (III) there is a relevant accepted use in clinical
practice that is not reflected in the approved labeling.'' \6\
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\6\ Section 503D(a)(1)(C) of the FD&C Act (21 U.S.C.
353d(a)(1)(C)).
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Additional Approaches. FDA has worked with applicants to submit
supplemental applications to add new uses to the labeling of approved
drugs in a wide range of therapeutic areas. For example, Project
Renewal is a public health initiative established by the FDA Oncology
Center of Excellence (OCE) that aims to update the Prescribing
Information (i.e., labeling for health care providers) and labeling for
patients for certain older oncology drugs to ensure that information in
the product labeling is clinically meaningful and scientifically up to
date. Aligned with FDA's mission to protect public health, this
initiative evaluates publicly available scientific evidence to update
the Prescribing Information and labeling intended for patients, so that
they contain a summary of the essential scientific information
necessary for safe and effective use of these drugs.\7\ Under Project
Renewal, to date, the labeling for three oncology drugs has been
updated to include new and revised indications, new and revised dosing
and administration recommendations, and new safety information: (1)
capecitabine for the treatment of colon, rectal, colorectal, breast,
gastric, esophageal, gastroesophageal junction, and pancreatic cancers;
\8\ (2) temozolomide for the adjuvant treatment of newly diagnosed
anaplastic astrocytoma and refractory anaplastic astrocytoma; \9\ and
(3) fludarabine phosphate for use as a component of a combination
regimen for the treatment of B-cell chronic lymphocytic leukemia (CLL),
and for the treatment of B-cell CLL in patients who have not responded
to or whose disease has progressed during treatment with at least 1
alkylating-agent containing regimen.\10\
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\7\ <a href="https://www.fda.gov/about-fda/oncology-center-excellence/project-renewal">https://www.fda.gov/about-fda/oncology-center-excellence/project-renewal</a>.
\8\ <a href="https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-updated-drug-labeling-including-new-indications-and-dosing-regimens-capecitabine">https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-updated-drug-labeling-including-new-indications-and-dosing-regimens-capecitabine</a>.
\9\ <a href="https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-new-and-updated-indications-temozolomide-under-project-renewal">https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-new-and-updated-indications-temozolomide-under-project-renewal</a>.
\10\ <a href="https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-updated-drug-labeling-fludarabine-phosphate-under-project-renewal">https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-updated-drug-labeling-fludarabine-phosphate-under-project-renewal</a>.
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Another approach has involved FDA initiating systematic analyses of
publicly available scientific literature, and upon determining that the
information supports findings that could result in labeling changes,
subsequently publishing Federal Register Notices to facilitate these
changes by encouraging the filing of supplemental applications. This
approach has resulted in labeling changes for drugs such as doxycycline
and penicillin G procaine for the treatment of inhalational exposure to
Bacillus anthracis (the bacterium that causes anthrax) \11\ and
penetrate calcium trisodium (Ca-DTPA) and penetrate zinc trisodium (Zn-
DPTA) for treatment of certain kinds of radiation exposure.\12\
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\11\ <a href="https://www.federalregister.gov/documents/2001/11/02/01-27493/prescription-drug-products-doxycycline-and-penicillin-g-procaine-administration-for-inhalational">https://www.federalregister.gov/documents/2001/11/02/01-27493/prescription-drug-products-doxycycline-and-penicillin-g-procaine-administration-for-inhalational</a>.
\12\ <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/calcium-dtpa-and-zinc-dtpa-drug-products-submitting-new-drug-application">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/calcium-dtpa-and-zinc-dtpa-drug-products-submitting-new-drug-application</a>.
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Recently, FDA approved a supplemental application for leucovorin
calcium tablets for the treatment of cerebral folate transport
deficiency in adult and pediatric patients who have a confirmed genetic
variant in the folate receptor 1 gene (CFTD-FOLR1).\13\ The approval
was based on a systematic review of the published literature on the
topic, including published case reports with patient-level information,
as well as mechanistic data. FDA collaborated with the applicant on a
process to update the labeling to include the essential scientific
information needed for the safe and effective use of the drug for
adults and pediatric patients with CFTD-FOLR1.
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\13\ <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency">https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency</a>.
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II. Topics for Public Input
FDA seeks public input from patient, clinical, public health, and
research communities on priority disease areas and potential candidates
for drug repurposing. In this Federal Register Notice, we are focusing
on FDA-approved drugs for which there currently appears to be no
commercial interest in adding a new use through a
[[Page 25899]]
supplemental application. Additionally, we are focusing on such drugs
that meet the following criteria for a new use: (1) There is compelling
scientific evidence to support the effectiveness of the drug for the
new use, (2) the dosage form(s) and route(s) of administration for the
new use are the same as for an approved indication, and (3) there is a
comparable safety profile for the patient populations for the new use
and approved indications. FDA is also seeking input on potential
candidates for drug repurposing that may not meet all of the above
criteria but have preliminary promising data that might address an
unmet need. In particular, FDA seeks comments, data (including real-
world data), and information on the following topics:
1. Priority areas: Initially identified priority chronic disease
areas include metabolic diseases, neurodegenerative conditions, women's
health conditions (e.g., conditions related to menopause), men's health
conditions (e.g., testosterone deficiency), and substance use
disorders, as well as rare diseases. Based on your understanding of
disease areas with significant unmet medical needs and high potential
for effective treatment through drug repurposing, do you agree with
these priority areas? Are there any other priority areas you would
recommend for inclusion? Please explain your response.
2. Candidates for drug repurposing: What candidates for drug
repurposing have the greatest potential for effective treatment of
particular identified medical conditions?
a. Scenario 1: Candidates for which sufficient evidence may already
exist to demonstrate their safety and effectiveness for a potential new
use.
For FDA to approve a new use, there needs to be data demonstrating
that the candidate is safe and effective for use under the conditions
prescribed, recommended, or suggested in the drug's labeling (section
505(d) of the FD&C Act). The substantial evidence standard is defined
in statute (section 505(d) of the FD&C Act) to mean evidence consisting
of adequate and well-controlled investigations, including clinical
investigations, by experts qualified by scientific training and
experience to evaluate the effectiveness of the drug involved, on the
basis of which it could fairly and responsibly be concluded by such
experts that the drug will have the effect it purports or is
represented to have under the conditions of use prescribed,
recommended, or suggested in the labeling or proposed labeling thereof.
The statute permits an approval based on one adequate and well-
controlled clinical investigation with confirmatory evidence if FDA
determines that the data are sufficient based on relevant science to
establish substantial evidence. The substantial evidence of
effectiveness standard ensures that sponsors have demonstrated the real
effect of a drug.
This scenario would be limited to candidates where no additional
data would need to be generated (e.g., from clinical trials), and it
may include potential uses for candidates based on publicly available
scientific evidence, such as published literature. Please submit ideas
for candidates that may have substantial evidence of effectiveness for
a new use of a drug for a disease or condition, as well as supporting
evidence from the published literature, unpublished adequate and well-
controlled investigations that have completed results and analyses, or
both.
b. Scenario 2: Candidates for which there are preliminary signals
from clinical data, but sufficient evidence does not yet exist to
demonstrate their safety and effectiveness for a new use.
There may be other situations in which there is information that
suggests the potential for a clinical benefit of a drug to treat a
disease or condition based on preliminary case reports or small pilot
studies, but for which larger adequate and well-controlled
investigations have not yet taken place. In these situations, the data
would not yet be sufficient to support a labeling change; however, they
may be suggestive of promising areas that warrant further study. Please
submit ideas for candidates that meet these criteria, as well as an
overview of the existing data which you believe is promising enough to
merit further study.
c. Scenario 3: Candidates for which there are preliminary signals
from pre-clinical data, but no clinical evidence yet exists to
demonstrate their safety and effectiveness for a new use.
There may also be situations in which there is information that
suggests the potential for a clinical benefit of a drug to treat a
disease or condition based on pre-clinical data--e.g., via high-
throughput screening, in vitro models, or artificial intelligence/
machine learning--but for which there is currently no clinical
evidence. Please submit ideas for candidates that meet these criteria,
as well as an overview of the existing data which you believe is
promising enough to merit further study.
3. Approaches to identifying candidates for drug repurposing: FDA
is also interested in exploring new innovative approaches to
identifying candidates for drug repurposing. Please describe methods or
opportunities that you believe the Agency could use to facilitate the
identification of new candidates.
4. Barriers and opportunities:
<bullet> In cases where there appears to be no commercial interest
in adding a new use through a supplemental application, what are the
barriers to repurposing drugs to address unmet needs?
<bullet> From the perspective of patients and clinicians, what are
the barriers to using FDA-approved drugs for unapproved uses when a
prescriber determines a drug is medically appropriate for a patient?
<bullet> What could FDA and other federal partners do to address
these barriers?
<bullet> How can FDA and other federal partners collect and use
data about unapproved uses for FDA-approved drugs to better understand
how they are being used in the community?
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-09366 Filed 5-11-26; 8:45 am]
BILLING CODE 4164-01-P
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