FDA Initiatives and Programs to Support Development of Treatments for Rare Diseases in 2026
FDA Initiatives and Programs to Support Development of Treatments for Rare Diseases in 2026
In the United States, there are over 7,000 rare diseases affecting more than 30 million people. Bringing a successful rare disease treatment to patients and families requires a clear understanding of the challenges along the regulatory approval path. These include a lack of validated endpoints or biomarkers, inability to use traditional clinical study designs, and uncertainty about what constitutes sufficient and robust evidence that enables the Food and Drug Administration (FDA) to confirm the safety and efficacy of new drugs.
Fortunately, the FDA offers critical support to help companies overcome regulatory challenges. In addition to its well-known Fast Track, Breakthrough Therapy designation, Accelerated Approval, and Priority Review programs, the FDA has developed many initiatives and programs to specifically support and expedite the development of medicines for rare diseases in the United States (US).
These offerings encourage companies to engage early with the FDA to receive specific guidance and help in study design development, endpoint validation, and more. These initiatives also help to overcome high development costs and bring therapies to market faster and more efficiently. This article reviews the existing FDA programs as per August 2026 that offer support and assistance to companies navigating the regulatory process for rare disease medicines.
Click the program name to jump to its description:
- Orphan Drug Act and Orphan Drug Designation
- Orphan Products Grants Program
- Rare Disease Cures Accelerator-Data and Analytics Platform
- Center for Biologics Evaluation and Research Rare Disease Program
- Center for Drug Evaluation and Research Accelerating Rare Disease Cures Program
- FDA Rare Disease Innovation Hub
- CDER/CBER Rare Disease Evidence Principles Process
- Rare Disease Endpoint Advancement Pilot Program
- Support for Clinical Trials Advancing Rare Disease Therapeutics Pilot Program
- Rare Pediatric Disease Designation and Priority Review Voucher Programs
- Public-Private Partnerships With the Critical Path Institute
- Public-Private Partnership for Ultra-Rare Cancers: Ultra-Rare Cancer Treatment Advancement Program
- Collaboration on Gene Therapies Global Pilot Program
- Complex Innovative Trial Design Paired Meeting Program
- Model-Informed Drug Development Paired Meeting Program
Orphan Drug Act and Orphan Drug Designation
The Orphan Drug Act (ODA) was enacted by Congress in 1983 to encourage the development of treatments for rare diseases by providing incentives to defray the costs. The ODA established the criteria and regulatory framework that allowed companies to apply for orphan drug designation (ODD) and benefit from these incentives. In addition, the ODA established the Orphan Product Grants Program to provide funding for product development for rare diseases or conditions, and the FDA Office of Orphan Product Development. Learn more about the ODA.
Any entity, whether foreign or domestic, public or private, for-profit or nonprofit (including state and local units of government) can apply for ODD. Foreign companies must have a registered US Agent to apply for ODD.
ODD qualifies sponsors for various incentives, including:
- Tax credits for qualified clinical testing
- Waiver of New Drug Application/Biologics License Application user fees
- Potential seven years of market exclusivity after approval
Eligibility criteria for ODD:
- Prevalence: the number of people affected by the disease or condition for which the drug is to be developed is fewer than 200,000 persons in the US (or if more, the drug may still qualify if there is no reasonable expectation that the cost of developing and marketing the drug will be recovered from sales in the first seven years after approval)
- Seriousness: life-threatening or serious disease or condition
- Medical plausibility: scientific rationale establishing a medically plausible basis for the drug’s use in the rare disease or condition
- Clinical superiority: of the drug over existing drug, if any
Orphan Products Grants Program
The Orphan Products Grants Program awards grants to clinical investigators to support the development of safe and effective medical products (drugs, biologics, medical devices, and foods for medical purposes) for patients with rare diseases or conditions.
Any entity foreign or domestic, public or private, for-profit or nonprofit (including state and local units of government) can apply for these grants. The funds promote and accelerate the development of innovative products for the treatment, prevention, and diagnosis of rare diseases. Funding opportunities are available on the FDA website and conditions depend on each type of grant.
There are three types of grants:
Clinical Trials Grants Program (began in 1983)
These grants fund clinical trials of products evaluating efficacy and/or safety in support of a new indication or change in labeling to address unmet needs in rare diseases or conditions. Through this program, the FDA awards between 5 and 12 new clinical trial grants for orphan products annually.
Natural History Studies Grants Program (began in 2016)
These grants fund well-designed, protocol-driven natural history studies (preplanned, observational study intended to track the course of the disease) that address knowledge gaps, support clinical trials, and advance rare disease medical product development.
FDA Rare Neurodegenerative Disease Grants Program (began in 2022)
These Awards grants and contracts cover the costs of research and development of interventions intended to prevent, diagnose, or treat amyotrophic lateral disease (ALS) and other rare neurodegenerative diseases in adults and children.
Rare Disease Cures Accelerator-Data and Analytics Platform
Through the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP®), led by the Critical Path Institute, the FDA aims to facilitate a cooperative, standardized approach to better characterize rare diseases, incorporate the patient’s perspective in clinical outcome assessment measures, and build clinical trial readiness in the pre-competitive space.
The RDCA-DAP provides a centralized and standardized infrastructure to share existing patient-level data (from clinical trials, observational studies, real-world data, and patient registries) and encourages the standardization of new data collection. Data are contributed from a variety of organizations and companies around the world, including patient groups, academic researchers, industry, consortia, data platforms, and collaborative networks.
This data sharing is meant to accelerate the understanding of rare disease progression, clinical outcome measures, and biomarkers, and facilitate the development of mathematical models of disease and innovative clinical trial designs.
Interested parties can contact the Critical Path Institute to discuss data contribution, collaboration opportunities, or participation in analytics discussions.
Center for Biologics Evaluation and Research Rare Disease Program
The FDA Center for Biologics Evaluation and Research (CBER) works to regulate biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies. CBER’s Rare Disease Program encompasses efforts to advance the development and timely approval of biologics to improve the lives of patients with rare diseases, including:
- Facilitating consideration of the patient perspective in regulatory decision-making, for example, by engaging with patient stakeholder organizations and participating in rare disease listening sessions
- Considering flexible and feasible regulatory approaches in review
- Contributing to the development and implementation of relevant regulatory policy and procedures
- Collaborating with rare disease colleagues across the FDA and other Federal agencies, international regulatory authorities, and outside organizations in cross-cutting activities, programs and initiatives
Center for Drug Evaluation and Research Accelerating Rare Disease Cures Program
The FDA Center for Drug Evaluation and Research (CDER) focuses on ensuring safety and effectiveness of prescription drugs, over-the-counter medications, and some biological therapeutics. Launched in 2022, the CDER Accelerating Rare disease Cures (ARC) Program is an initiative to speed up and increase the development of rare disease drugs by bringing together CDER’s collective expertise and activities, promoting innovative scientific design, providing a deeper understanding of regulatory policies, and engaging with patients and their advocates, academic researchers, clinicians, and drug developers.
Learning and Education to Advance and Empower Rare Disease Drug Developers Initiative
This initiative, known as LEADER 3D, was launched in 2022 and is managed by CDER’s Rare Diseases Team under the ARC Program. LEADER 3D aims to facilitate the development of safe and effective drugs to treat rare diseases through expanded stakeholder communication and education. This includes developing educational materials like case studies that illustrate challenges faced by applicants for their rare disease CDER-regulated drug or biologic product and the associated regulatory considerations and solutions developed with the FDA. New case studies are published regularly.
FDA Rare Disease Innovation Hub
The FDA Rare Disease Innovation Hub, established in June 2024 and co-led by the Directors of CDER and CBER, aims to leverage the activities of the CDER ARC Program and CBER Rare Disease Program and enhance existing cross-center collaborations. The Hub focuses on facilitating development of medical products for rare diseases, particularly those intended for smaller populations or for diseases where the natural history is variable and not fully understood. The Hub provides a forum for sharing expertise and promoting alignment on complex scientific challenges, evolving science, and novel clinical trial approaches particularly for issues common to multiple diseases or a class of diseases.
The Hub has sponsored the Rare Disease Innovation, Science, and Exploration (RISE) workshop series since September 2025 to address scientific and regulatory challenges common across rare diseases. Topics discussed so far include challenges of conducting clinical trials in rare disease small and diminishing populations, science and regulatory environment for individualized therapies, and data sharing to inform development and regulatory review for rare disease therapies.
CDER/CBER Rare Disease Evidence Principles Process
A new joint CDER-CBER review process under Rare Disease Evidence Principles (RDEP) was announced by the FDA in September 2025. The goal is to facilitate the approval of drugs to treat rare diseases with very small patient populations, significant unmet medical need, and a known genetic defect that is the major driver of the pathophysiology. The RDEP process offers the assurance that drug review will encompass additional supportive data. Approval under the process may be based on one adequate and well-controlled study plus robust confirmatory evidence, which may include:
- Strong mechanistic or biomarker evidence of the drug’s treatment effect on the direct pathophysiology of the disease
- Evidence from relevant non-clinical models
- Clinical pharmacodynamic data
- Case reports, expanded access data, or natural history studies
Eligibility criteria:
Sponsors may apply for the RDEP process at any time prior to the launch of a pivotal trial if the investigative therapy is specific to the correction of the genetic defect in question (i.e., either correcting the gene or is a replacement of an essential physiological protein that is otherwise deficient due to the gene defect) and meets the following criteria:
- Drug is for a very small, rare disease population or subpopulation (e.g., generally less than 1,000 persons in the US)
- Drug is intended to treat a known, in-born genetic defect that is the major driver of the pathophysiology
- Clinical course of the disease is progressive deterioration in function leading to rapid and/or significant disability or death in a relatively short period of time
- No adequate alternative therapies exist that alter the course of the disease
Sponsors can submit a request to be reviewed under the RDEP process as part of a formal meeting request and must file it before a pivotal trial begins. Accepted sponsors will have an initial meeting with the appropriate FDA review team to determine what data will be used to substantiate safety and effectiveness, with patient and expert input encouraged throughout, and to discuss the need for future engagement and interactions with the agency during drug development. Sponsors developing drugs for rare cancers should first consult with the FDA Oncology Center of Excellence or relevant review divisions to determine if this process applies.
Rare Disease Endpoint Advancement Pilot Program
A joint CDER-CBER pilot program, the Rare Disease Endpoint Advancement (RDEA) program, was launched in 2023 to support novel endpoint efficacy development for drugs that treat rare diseases by providing a mechanism for sponsors to collaborate with the FDA throughout the efficacy endpoint development process.
RDEA is for sponsors with an active IND or pre-IND for a rare disease developing novel efficacy endpoints, or sponsors who do not yet have an active development program but have, or are initiating, a natural history study where the proposed endpoint is intended to be studied. Sponsors can be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization.
RDEA offers increased engagement with FDA experts from CDER/CBER via a series of focused meetings to discuss novel efficacy endpoints intended to establish substantial evidence of effectiveness for rare disease treatments.
As the FDA can only accept a maximum of three proposals per fiscal year, the Agency gives preference to proposals that can impact drug development more broadly or reflect a range of different types of endpoints, for example.
Support for Clinical Trials Advancing Rare Disease Therapeutics Pilot Program
Support for Clinical Trials Advancing Rare Disease Therapeutics (START) is a joint CDER-CBER pilot program initiated in 2024. It aims to augment the currently available formal meetings between the FDA and sponsors through more rapid and ad-hoc communication mechanisms to address issues related to the development of individual products, such as clinical trial design, choice of control group, or patient population.
Selected sponsors receive more frequent advice related to specific issues to facilitate novel drug development programs and generate high quality and reliable data intended to support a new drug or biologics license application.
Eligibility criteria:
- For both CBER and CDER: sponsors of products currently in clinical trials under an active IND
- For both CBER and CDER: sponsors who have demonstrated substantial effort to ensure that chemistry, manufacturing, and controls development aligns with clinical development
- For CBER: gene or cellular therapy intended to address an unmet medical need as a treatment for a serious rare disease or condition, which is likely to lead to significant disability or death within the first decade of life
- For CDER: products intended to treat rare neurodegenerative conditions, including those of rare genetic metabolic etiology
Rare Pediatric Disease Designation and Priority Review Voucher Programs
The Rare Pediatric Disease Designation (RPDD) and Priority Review Voucher (PRV) programs aim to incentivize drug development for rare pediatric diseases. PRVs can be awarded by the FDA to sponsors of rare pediatric disease product applications that meet certain criteria. Under this program, a sponsor who receives approval for a drug or biologic for a rare pediatric disease may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.
RPDD can be requested for a novel drug product intended to prevent or treat a rare serious or life-threatening disease affecting patients from birth to 18 years, with supportive data suggesting that the drug could be effective in this indication. Note: the FDA does not require the same level of supportive data compared to ODD requests.
Any entity foreign or domestic, public or private, for-profit or nonprofit (including state and local units of government) can request an RPDD and then a PRV when submitting their New Drug Application/Biologics License Application. Foreign companies must have a registered US agent to apply for RPDD. Drugs containing a previously approved active ingredient are not eligible for the rare pediatric disease PRV program.
A PRV speeds up FDA review to six months from the standard 10 months. The sponsor may also transfer or sell the voucher to another sponsor.
The rare pediatric disease PRV program was extended in February 2026 and will sunset after September 30, 2029.
Public-Private Partnerships With the Critical Path Institute
CDER partners with the Critical Path Institute under the ARC Program on several rare disease projects, such as the Critical Path for Lysosomal Diseases Pre-Consortium and the Critical Path for Rare Neurodegenerative Diseases. These public-private partnerships connect various rare disease stakeholders such as advocacy groups, academics, drug developers, patients, and other partners with the FDA to help identify solutions for challenges in rare disease drug development. Participants benefit from collecting and sharing data to address knowledge gaps in rare diseases.
Interested parties are encouraged to contact the Critical Path Institute directly.
Public-Private Partnership for Ultra-Rare Cancers: Ultra-Rare Cancer Treatment Advancement Program
In January 2026, the Foundation for the National Institutes of Health launched the design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), in collaboration with the National Institutes of Health and the FDA Oncology Center of Excellence. This new public-private partnership is dedicated to accelerating the development of innovative ultra-rare cancer treatments. ULTRA will reduce hurdles to accessing new therapies by conducting end-to-end therapeutic development for selected ultra-rare cancers with well-established biologic vulnerabilities and limited economic incentive for drug development. Two indications have been selected as pilot: clear cell sarcoma and desmoplastic small round cell tumors. More will follow if the pilot projects are successful. Operational and scientific strategy from the program will be shared with the community via an open drug-development platform, supporting the development of a reproducible model from the identification of the drug candidate to the regulatory approval, marketing, and sustainable supply.
ULTRA welcomes involvement from scientific, government, and patient communities with expertise in the selected indications and in ultra-rare cancers or oncology drug development in general.
Collaboration on Gene Therapies Global Pilot Program
The Collaboration on Gene Therapies Global Pilot Program is an initiative to explore the potential for concurrent and collaborative regulatory review of gene therapy applications for rare diseases by global regulatory partners, including the World Health Organization and members of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. The goal is to increase the efficiency of the regulatory process, reducing time and cost for agencies and sponsors. Although this program was announced in early 2024, the FDA has not yet published guidance on eligibility criteria or procedures. Alira Health continues to monitor FDA communications for updates.
Complex Innovative Trial Design Paired Meeting Program
The Complex Innovative Trial Design (CID) Paired Meeting Program, led by statisticians in CDER and CBER, was established to facilitate and advance the use of complex adaptive, Bayesian, and other novel clinical trial designs. While not specific to rare diseases, this program can be particularly helpful for the development of rare disease drugs where novel clinical trial approaches are sometimes needed. To promote innovation in this area, the FDA has published some case studies that present trial designs developed through the meeting program.
Any sponsor developing drugs or biologics, including industry, public institutions, academic centers, and non-profit organizations, is eligible for the CID Paired Meeting Program.
This program offers selected sponsors an opportunity for increased engagement via initial and follow-up meetings with FDA experts from the CDER and/or CBER to discuss CID and analyses in medical product development.
Eligibility criteria:
- The Sponsor has a Pre-IND or IND number for the medical product included in the CID meeting request
- The trial is not a first-in-human study, and there is sufficient clinical information to inform the proposed CID
- The Sponsor and FDA are able to reach agreement on the trial design information to be publicly disclosed
Under the CID Paired Meeting Program, the FDA selects one to two eligible and appropriate proposals per quarter each year (i.e., up to eight per year).
Model-Informed Drug Development Paired Meeting Program
The Model-Informed Drug Development (MIDD) Paired Meeting Program advances and integrates the development and application of exposure-based, biological, and statistical models derived from preclinical and clinical data sources in drug development and regulatory review. While MIDD can be applied to all therapeutic areas, rare diseases have a greater need for MIDD because of the smaller number of patients available for studies.
Applications are open to any sponsor including industry, public institutions, academic centers, and non-profit organizations developing drugs or biologics. Interested consortia or software/device developers can participate in partnership with a drug development company.
Selected sponsors receive an opportunity for increased engagement via initial and follow-up meetings with FDA experts from the CDER and/or CBER to discuss MIDD approaches in medical product development.
Eligibility criteria:
- Drug/biologics development company with an active IND or Pre-IND number for the relevant development program
- This excludes statistical designs involving complex adaptations, Bayesian methods, or other features requiring computer simulations to determine the operating characteristics of a confirmatory clinical trial
Under the MIDD Paired Meeting Program, the FDA accepts one to two paired-meeting requests quarterly each year (i.e., up to eight per year) throughout the PDUFA VII period (2023-2027).
A new guidance, ICH M15 ‘General Principles for Model-Informed Drug Development’, was released in June 2026 and is intended to facilitate a multidisciplinary understanding of MIDD and associated evidence generation to support drug development and regulatory decision-making. The guidelines describe the principles of MIDD, including recommendations on MIDD planning, model evaluation, and evidence documentation. Use of this guidance in preparing MIDD Paired Meeting requests and packages is recommended.
Conclusion
Developing treatments for rare diseases is a complex journey marked by scientific, clinical, and regulatory hurdles. With over 30 million Americans affected by rare diseases, the need for effective therapies is urgent. The FDA has responded with a robust suite of initiatives, programs, and partnerships that provide critical regulatory support, encourage innovation, and reduce development barriers. By leveraging these resources, pharmaceutical companies can navigate the regulatory pathway more efficiently and bring much-needed treatments to patients and families faster.
At Alira Health, we continuously monitor the FDA’s guidance on rare disease treatments and work with our clients to help you take full advantage of the available support. We help companies develop and commercialize rare disease treatments with the intense focus on the unique needs of rare disease patients that is crucial to your success. With a continuum of patient-centric solutions, we work with you to successfully develop and provide life-changing treatments to the patients.
Expert insights
provided by:
Caroline Snacke, Regulatory Affairs Manager
Expert insights
provided by:
Caroline Snacke,
Regulatory Affairs Manager
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