Rare disease round-up: FDA efforts to advance treatments

FDA’s posted agenda for Rare Disease Day 2026 evinces a dual emphasis on patient viewpoints and accelerating cures, with panels scheduled to discuss patient-focused agency initiatives, patient engagement opportunities, the promises and perils of AI, and utilizing real-world data (RWD) and real-world evidence (RWE) at FDA.

What’s happening with the Hub?

In July 2024, FDA established its Rare Disease Hub, to serve as a point of collaboration and connectivity between Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) with the goal of ultimately improving outcomes for patients. FDA said the hub will work across rare diseases, with a particular focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood.

On February 2, FDA released the 2026 Strategic Agenda for the Hub. The agenda touts three accomplishments from 2025:

1. The Rare disease Innovation, Science, and Exploration (RISE) workshop series, which focuses on issues common to development of therapies for multiple rare diseases and for which innovative methods and evolving regulatory science may offer valuable solutions.
2. The Rare Disease Policy and Portfolio Council (RDPPC), a cross-Center collaborative body that meets monthly to convene senior medical product leadership and subject matter experts from CBER and CDER to align on regulatory approaches regarding complex challenges in rare disease drug development relevant to both Centers.
3. The creation of a public-facing email address and website to promote contact with the rare disease community and to facilitate the sharing of information about Hub initiatives.

Looking ahead, the Hub’s strategic agenda clarifies that FDA will prioritize the following goals:

1. Advance regulatory science of rare disease therapies, including by enhancing opportunities for consideration of novel endpoints, biomarker development and assays, innovative trial design, RWE, and statistical methods. Toward this end, FDA will continue to promote its RISE workshops, with the next one scheduled for March 30, 2026.
2. Strengthen coordination between medical product Centers, including alignment on review standards and decision-making, with future RDPPC meetings to regularize cross-Center communication regarding the same or related diseases or issues.
3. Create a centralized point of contact for external partners, including an FDA website consolidation project, and publication of a GovDelivery rare disease focused newsletter.

Accelerating rare disease development

In addition to FDA’s rare disease hub goals, we anticipate that the following hot topics will be discussed at FDA Rare Disease Day 2026:

• Plausible mechanism pathway. In November 2025, FDA leaders published an article in the NEJM outlining a new “plausible mechanism pathway,” under which a drug or biologic manufacturer may be able to obtain FDA marketing authorization for products targeting specific, well-understood genetic abnormalities, as we described online here. This approach is not intended to be limited to rare disease treatments. Instead, this approach intends to address areas of unmet need where traditional trials would be infeasible, and where data from such bespoke treatment can inform regulatory decisions regarding the product. We see the plausible mechanism pathway as an extension of FDA's increasing willingness to use its regulatory flexibility and recognizing the challenges in the development of drugs and biologics for rare diseases, unmet need, regenerative medicines, and “n-of-1” therapies in particular. FDA has promised to soon provide more information about this pathway, and we are hopeful that will be released in the coming weeks. A draft of a guidance document for this new pathway was recently circulated to White House for review.
• RDEP. In September 2025, FDA had announced its “Rare Disease Evidence Principles” (RDEP), under which eligible drugs and biologics for ultra-rare diseases caused by known genetic defects will receive assurance of FDA consideration of additional supportive data that may be used to meet regulatory approval standards, as we summarized at the time online here. For programs meeting the eligibility requirements, FDA said it will offer an additional meeting with the appropriate review team, which could help determine what data could be used to demonstrate “substantial evidence” of effectiveness. Although this process does not alter the statutory standard for approval, it evinced FDA’s focus on considering a range of evidence that may be used to establish substantial evidence and will communicate that to sponsors earlier in development.
• Real-world evidence use. When clinical trials struggle to enroll patients, as is often the case for rare diseases, sponsors employ creative tactics to use RWD to support bids for approval, including turning to natural history cohorts. On December 15, 2025, FDA issued a press release (which we analyzed at the time online here), stating that it will accept RWE without requiring that identifiable individual patient data collected from RWD sources always be included in a marketing submission. Instead of requiring private, confidential information at the individual patient level, FDA said its reviewers will now consider the strength of submitted RWE on an application-by-application basis. FDA stated that this policy change opens the door to using de-identified databases containing millions of patient records, “including national cancer registries like the National Cancer Institute’s Surveillance, Epidemiology, and End Results, hospital systems databases, insurance claims databases, and electronic health record networks.”
• CMC guidance for cell and gene therapies. On January 11, 2026, FDA issued an update on its flexible approach to overseeing chemistry, manufacturing, and control (CMC) requirements for cell and gene therapies, which FDA said it expects to help expedite product development and guide the evaluation of development strategies necessary for the preparation of biologics license application (BLA) submissions. Although the update largely reflected existing FDA policy, it consolidated information for sponsors, again demonstrating the agency’s prioritization of expediting developments of treatments for rare diseases and biological products more broadly. When asked about the guidance at a Hogan Lovells panel on the edges of the J.P. Morgan Healthcare Conference, FDA leaders agreed that the update aggregates flexibilities described in other forums into a single more accessible resource.

Against the backdrop of FDA’s efforts to promote therapies that treat rare diseases, we also note that recent months have seen agency rejections of rare disease treatment candidates, particularly for sponsors seeking accelerated approval to treat ultra-rare diseases. The regulatory environment remains uncertain for use of certain surrogate biomarkers. As high-profile FDA decisions are expected in coming months, we will be closely monitoring how the agency reconciles its commitment to rare disease innovation with its regulatory decision making.

Legislative action

• Rare pediatric disease priority review vouchers. On February 3, President Trump signed into law the “Mikaela Naylon Give Kids A Chance Act” as part of the Consolidated Appropriations Act (CAA) of 2026, which reauthorized the Rare Pediatric Disease Priority Review Voucher (PRV) Program until 2029, as we recently discussed online here. These PRVs are granted to sponsors of therapies that treat rare “serious or life-threatening diseases in which the serious or life-threatening manifestations affect individuals aged from birth to 18 years.” The CAA extended FDA's authority to grant rare pediatric disease PRVs until September 30, 2029, and further provided that FDA may no longer issue vouchers after that date.
• Catalyst orphan drug exclusivity. The CAA also codified FDA’s longstanding interpretation of the scope of orphan drug exclusivity (i.e., a statutory “fix” to the Catalyst v. Becerra decision). In Catalyst, the Eleventh Circuit held that, under the plain language of the statute, orphan drug exclusivity blocks approval of the drug for the full designated disease or condition (not only the approved indication). As amended by the CAA, the Orphan Drug Act now specifies that exclusivity protects only the approved use or indication within the designated rare disease or condition. Our client alert on this change, along with other CAA changes, is available here.

Next steps

Registration for FDA Rare Disease Day is available online here, and the agency is open to receiving questions ahead of the event. We generally applaud FDA’s ongoing regulatory science and transparency initiatives, and also observe that the rare disease community may be able to benefit from greater clarity around certain evolving policies, such as the “plausible mechanism” pathway.

If you are a sponsor of a treatment for a rare disease, or may have questions on FDA regulatory approval processes more generally, feel free to reach out to any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

Authored by Elizabeth Jungman, Komal Nigam, Eman Al-Hassan, and Eva Schifini