Rare Disease Month Developments, Part 1 – The Good: RPD PRV Program Renewed, FDA Rare Disease Hub’s 2026 Strategic Agenda & Plausible Mechanism Draft Guidance On Its Way

February is Rare Disease Month, designated as such to raise awareness and to support the millions of individuals affected by rare diseases.  It is also an extremely meaningful time for those of us at HPM who work regularly with sponsors to help get therapies to patients suffering with rare diseases despite the unique challenges getting these through the FDA approval gauntlet.  That’s why we are thrilled to see this month start off with a bang, including the long-awaited renewal of the Rare Pediatric Disease Priority Review Voucher (“RPD PRV”) program, the publication of FDA’s Rare Disease Innovation Hub’s Strategic Agenda for 2026, and a draft guidance on the Plausible Mechanism Pathway under review.  At the same time, we have seen recent reminders that such challenges persist, which we will cover in a Part 2 blog post in the coming days.

The Rare Pediatric Disease Priority Review Voucher Program Renewed

One persistent challenge in rare disease drug development is securing funding to develop such drugs for relatively small numbers of patients.  As we have highlighted in multiple recent blog posts (here and here), the Rare Pediatric Disease Priority Review Voucher (“RPD PRV”) program has been a very effective mechanism in addressing this challenge.  The RPD PRV provisions allow FDA to award a transferable priority review voucher upon approval of a drug intended to treat a rare disease that primarily affects pediatric patients.  This voucher can be used by the recipient to secure priority review for another of its products, or it can be sold to another developer.  The sale of these vouchers, the price of which had settled in the $100 million range before rising with the recent prospect of the expiration of the program, provides substantial support to make the development of drugs for rare diseases financially viable.

As we previously blogged, an analysis from NORD (updated in November 2025), showed that 63 RPD PRVs had been awarded across 47 rare pediatric diseases; of these 47, only four had any FDA-approved treatments prior to these approvals.  This is clear evidence that the RPD PRV program has been effective in incentivizing rare pediatric disease drug development.  However, the program has always had built-in sunset dates: the first is the date after which FDA no longer has the authority to grant an RPD PRV for a drug that had not been previously designated as a drug for a rare pediatric disease prior to that date; the second deadline is the date after which no RPD PRVs may be granted at all.  Notably, the program was reauthorized prior to the occurrence of sunset dates in 2016 and 2020, each time for 4 additional years.  In 2024, as time was ticking away toward this first deadline, it appeared as if there was a deal to renew the program again, but it was stripped out of the government funding bill at the last minute.  Since that time, we have been living in this limbo between deadlines, with the final deadline of September 30, 2026, beginning to come into view even as Congress made small movements toward renewal.

Understandably, this uncertainty had a substantial impact on rare pediatric disease drug development.  This made necessary funding more difficult to obtain, and it made development planning extremely challenging as companies developing products that received rare pediatric disease designations were being forced to consider rushing to submit applications in order to attempt to get approval by the September deadline.  We have heard over and again from our clients about how crucially important an extension would be for their programs and rare disease drug developers broadly.  And we hope we don’t see a wave of Complete Response Letters for applications submitted in late 2025/early 2026 where timing may have been pushed up to get an action date before the end of September.

All of this is why we were so pleased to see Congress finally get an extension across the finish line.  On February 3, 2026, Congress passed legislation (H.R.7148 – Consolidated Appropriations Act, 2026) to end the recent partial government shutdown, and the President signed it into law.  Within this package of legislation was the Mikaela Naylon Give Kids a Chance Act, which renewed the RPD PRV program until its new expiration date of September 30, 2029.  Notably, the law does away with the two-part sunset date, so now there is only a single expiration date for the program after which FDA will not be able to grant vouchers absent an additional reauthorization.

We also wish to applaud FDA, which had continued to grant rare pediatric disease designations, although such designations could not, at the time, qualify programs for RPD PRVs.  As we previously noted, this should allow for a more seamless transition for the program with its renewal.  This is a tremendous benefit to the rare disease community and a great start to Rare Disease Month.

FDA Shares the Rare Disease Innovation Hub’s 2026 Strategic Agenda

Another meaningful piece of rare disease drug development news to highlight as we kick off Rare Disease Month is the release of FDA’s Rare Disease Innovation Hub’s Strategic Agenda (“the Agenda”).  The Rare Disease Innovation Hub (“the Hub”), which we applauded when it was launched in 2024, just completed its first full year of existence.  The Hub is a cross-center program designed to serve as a point of engagement with outside parties on rare disease issues, as well as a forum for CDER and CBER to collaborate on cross-cutting rare disease issues.  The Hub was established to focus on three primary functions, according to the original announcement: (1) “Serve as a single point of connection and engagement with the rare disease community…for matters that intersect CDER and CBER”; (2) “Enhance intercenter collaboration to address common scientific, clinical and policy issues related to rare disease product development…and promote consistency across offices and Centers”; and (3) “Advance regulatory science with dedicated workstreams for consideration of novel endpoints, biomarker development and assays, innovative trial design, real world evidence, and statistical methods.”

Following its first full year, the Hub’s 2026 Strategic Agenda offers an opportunity to reflect on efforts made in furtherance of these three primary functions in 2025 as well as goals for 2026.  This Agenda notes that “with no dedicated budget for 2025 and no full-time staff apart from its Director,” the Hub made progress in 2025.  The Agenda highlights that the Hub has received dedicated funding of $250,000 from CBER and $750,000 from CDER to fund a small staff and facilitate activities in 2026 as it seeks to further advance these three core goals:

1.  Further Advance Regulatory Science of Rare Disease Therapies

The Agenda highlighted the two recent Rare disease Innovation, Science, and Exploration (“RISE”) Workshops (one of which we blogged about here) focusing on control arm options for rare disease clinical trials and on individualized therapies.  The RISE series was announced in the 2025 Strategic Agenda.

For 2026, the Hub is planning up to three RISE workshops, with topics to be selected from proposals submitted by the rare disease community (the March 2026 meeting will be discussing data sharing across the rare disease ecosystem).  The Hub is also planning a 2026 program on the role of the patient voice in informing drug development.

2. Enhance and Strengthen Coordination and Alignment Between Medical Product Centers

The Agenda highlighted the launch of the Rare Disease Policy and Portfolio Council (“RDPPC”) (we also blogged about this here) as a cross-center body that meets monthly with senior leadership and subject matter experts to align on regulatory approaches for rare disease drug development applications (although highlighted as a 2025 accomplishment, it was announced in 2024 and included in the 2025 Strategic Agenda).  RDPPC discussions led to the creation of an internal working group, “a more regularized internal process for cross-center connections…when the Centers are addressing novel or complex issues in rare disease drug development,” and a public workshop regarding novel efficacy endpoints in ophthalmologic rare disease drug developments where the standard visual acuity endpoints are not appropriate.  Additionally, the Agenda highlighted the announcement of the Rare Disease Evidence Principles (“RDEP”) (we also blogged about this here), which is designed to establish that substantial evidence of effectiveness for drugs for ultra-rare diseases may, in certain circumstance, generally be met based on one adequate and well-controlled study that may be a single-arm trial supported by confirmatory evidence.

For 2026, the Hub announced its intention to build on the success of its efforts to encourage Agency-wide coordination on rare disease approaches “to ensure that drug review within the Centers have common approaches when evaluating similar populations or issues.”  The Agenda also describes FDA’s Annual Rare Disease Training for Reviewers to discuss common rare disease challenges and promote best practices for review of such applications.  In the Agenda, the Hub announced a Rare Disease Review Staff Training Feedback pilot program to solicit topics for this program from the rare disease community for the 2026 training, which may also include a meeting with industry and other stakeholders.

3.  “Create a Centralized Point of Contact for External Partners”

The Agenda highlighted the launch of its website and email address (RDInnovationHub@fda.hhs.gov) to promote contact with the rare disease community, as well as a forthcoming report with recommendations for future FDA public-facing educational offerings focused on biologics development and the role of patient and disease advocates in development.

For 2026, the Hub also intends to publish a quarterly newsletter regarding news, including noteworthy approvals, and rare disease programs across FDA.  In addition, the Hub plans, subject to resource constraints, to undertake a website consolidation project to make rare disease program information more accessible to the community, which may result in a single website covering all such programs.  The Hub, in collaboration with CDER and CBER, will also host FDA Rare Disease Day 2026 on February 23 (an event which was cancelled last year and we are glad to see return).

Overall, the Agenda does not reflect major changes from the 2025 Agenda, which discussed the RISE workshops, patient and community engagement, and cross-center coordination and alignment (as well as the establishment of the RDPPC).  The surprise announcement of the RDEP program in September 2025 was not forecast in the 2025 Agenda, but was highlighted as an accomplishment nevertheless.  As such, the 2026 Agenda may not fully encompass the developments we can expect from FDA in the rare disease drug development world.  Further, there is the opportunity to help shape the Hub’s focus, as it is currently seeking input on future RISE workshop topics here.

Draft Guidance on the Plausible Mechanism Pathway Under Review

One hope we have is that FDA will elucidate in clear regulatory terms the nature, scope and limits of its “Plausible Mechanism” pathway which we think has tremendous potential to create a formal regulatory system to enable FDA regulators to approve novel therapies for classes of rare conditions where it is difficult to conduct randomized, concurrently-controlled trials.  We understand that a draft guidance is under review at the Office of Management and Budget, focused on the initial use case for this pathway – individualized therapies.  We eagerly await this and the opportunity to provide comments as we would wish to encourage FDA to consider more detailed guidance on how to leverage this pathway in a broader range of rare disease settings.

Since the start of the rare disease era in 1983, FDA officials have had to act idiosyncratically (and at the risk of being called out by their peers for going outside the boundaries of existing regulatory pathways or, in other words, what we have elsewhere referred to as “coloring outside the lines”) in order to approve orphan drugs, especially for ultra rare conditions, even when it is the correct scientific course and their approvals advance the health of Americans.  When FDA articulates in clear regulatory terms the practical ways in which it intends to implement the “plausible mechanism” pathway, it may open up a whole new era of rare disease development before us.

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With all of this, these authors, Mark, James and Frank, are encouraged by the start to Rare Disease Month, and we are ready and eager to lend our support to accomplishing more in this year ahead by tackling head-on all the considerable work still to be done.  Stay tuned for our Part 2 blog post where we highlight some of those challenges.

We hope to see you at Rare Disease Week in our nation’s capital. Onward together!