Developing treatments for rare diseases is one of the most pressing challenges in healthcare. More than 10,000 rare conditions affect an estimated 30 million Americans, yet only a few hundred have an approved therapy. Recognizing this urgent need, the U.S. Food and Drug Administration (FDA) recently re-issued a Notice of Funding Opportunity (NOFO) for RFA-FD-23-001 to fund clinical trials of products intended to address unmet needs in rare diseases or conditions.   

The funding opportunity would grant successful applications up to $650,000 per year for up to four years.  Applicants may request additional funding over the above listed maximum for innovative and efficient trial approaches. The additional funding request shall not exceed an additional $250,000 total costs per year (to a maximum total award cost of $900,000 per year) for up to 4 years.  

Applications for this grant are due October 21, 2025 by 11:59 PM Eastern Time. The NIH encourages apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

If you are pursuing an Orphan Drug Designation (ODD) or are already engaged in rare disease research, this grant could provide the financial support and regulatory pathway alignment you need to bring your therapy closer to patients.

Who Qualifies?

To be eligible, your product must target a rare disease or condition as defined by U.S. law:

• Chronic conditions: Prevalence of fewer than 200,000 people in the U.S.
• Acute conditions (lasting under a year): Annual incidence of fewer than 200,000 cases in the U.S.
• Diagnostics or vaccines: Target population must be fewer than 200,000 people annually.

While it is not strictly required to obtain an Orphan Drug Designation prior to submitting a grant application, it makes the process much smoother. If you have already been granted an ODD for your program, you will have already addressed a number of the qualification criterium with the FDA.

For example, when submitting the grant application, applicants must provide data and citations for prevalence or incidence to prove that the target is a rare disease or condition. If your therapy is for a subset of a more common disease, you must identify an “Orphan Subset” by justifying why your drug would not be appropriate for use outside that subset. This is typically due to mechanism of action, potential toxicity, or prior clinical evidence.

If you have already been granted an ODD, the FDA has already determined that your program targets a rare disease or an orphan subset. In this case, applicants will need to include the Orphan Drug Designation number and date of designation.

Applicants must also have an active IND (Investigational New Drug) or IDE (Investigational Device Exemption). The protocol associated with the grant application must have been submitted to applicable FDA review division at least 30 days before the grant application deadline.

What the Grant Covers

The funding supports clinical trials from Phase 1 through Phase 3 that evaluate the safety and/or efficacy of a product for a rare disease. Proposals must be tied to a specific new indication or labeling change. Studies without a clinical trial component are not eligible for funding.

How to Apply

The application forms for this grant must be accessed through ASSIST, Grants.gov workspace, or an institutional system-to-system solution. NIH stresses that it is critical for applicants to follow the instructions outlined in the “How to Apply – Application Guide”[1]. Compliance with the instructions provided in the Research (R) Section of the How to Apply-Application Guide is strictly enforced and applications submitted out of compliance may be not accepted for review by NIH.

What Makes a Strong Application

Applications will be evaluated by NIH on scientific and technical merit. Successful applications typically include:

• Clear Rationale: The soundness of rationale in relation to the current understanding of the target rare disease and the likelihood that the proposal will address unmet needs in the rare disease.
• Study Design: The quality and appropriateness of the study design, research methodology, and data analyses to accomplish the specific aims of the proposed study and its potential to make an impact on rare diseases.
• Innovative and Efficient Clinical Trial Designs: FDA is interested in supporting innovative and efficient trial designs such as seamless and adaptive trial designs, which compress the phases of a trial into one continuous trial, as well as basket, umbrella and platform trials, which allow for testing of multiple drugs and/or multiple diseases using a common infrastructure.
• Inclusion of Patient Input: The inclusion of patient and caregiver perspectives in the planning and design of the clinical study to improve protocol design and medical product development.
• Ability to Advance the Current Field: The ability of the project to shift current research or clinical practice paradigms towards future product development and to exert a significant influence on product development.

How Bracken Can Help

Bracken has deep expertise in orphan drug development, regulatory strategy, and clinical trial design. We can:

• Assess your eligibility for the grant and Orphan Drug Designation
• Support ODD and IND applications as well as other regulatory submissions
• Help design an innovative and competitive clinical trial strategy
• Prepare compelling grant narratives and required documentation

From initial concept to final submission, we can help ensure your proposal is both scientifically rigorous and strategically aligned to maximize your chances of success. Contact us to learn more about opportunities for support. 

[1] https://grants.nih.gov/grants-process/write-application/how-to-apply-application-guide