In an era of healthcare reform and heightened scrutiny of pharmaceutical innovation, America’s leadership in rare disease drug development stands out as a remarkable achievement. This progress has been shaped by the dedication of the rare disease patient community—families and advocacy organizations like the National Organization for Rare Disorders (NORD), the Friedreich’s Ataxia Research Alliance (FARA), the Cystic Fibrosis Foundation, and countless smaller patient groups that have driven and often directly sponsored research and clinical trials. Alongside them, the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have played a crucial role in fostering innovation through targeted initiatives, balancing efficiency with safety, and setting the global standard for rare disease approvals. For instance, the 1983 Orphan Drug Act incentivized development with tax credits and market exclusivity, resulting in over 1,100 orphan drugs approved in the U.S. since its enactment, compared to only a handful before. This model has been so successful that it influenced similar legislation worldwide, including Japan’s 1993 and the European Union’s 2000 orphan drug policies. It also spurred a robust orphan drug industry—today, orphan drugs account for nearly 20% of global prescription drug sales and the global orphan drug market exceeds $170 billion. The U.S.’s forward-looking policies have attracted substantial investment in rare disease research, supporting high-value biotech jobs and delivering cutting-edge therapies to patients worldwide.
The U.S. as a Global Leader: Why It Matters
The United States has established itself as the epicenter of orphan drug development, largely due to the efforts of families, the forward-looking policies of the FDA, and an infrastructure supporting innovation. The passage of the Orphan Drug Act in 1983 set the foundation for this leadership by incentivizing the development of treatments. Only 38 orphan drugs existed before 1983, but since then hundreds of rare disease treatments have reached the market, a testament to the Act’s impact. Beyond incentives, the U.S. fosters an environment where patient organizations, regulatory agencies, and pharmaceutical companies work together in true partnership. This collaborative spirit has driven the development of novel regulatory pathways that make clinical trials more efficient and patient-centered. Programs such as the FDA’s Accelerating Rare disease Cures (ARC) initiative and the newly established Rare Disease Innovation Hub demonstrate the agency’s proactive approach to reducing barriers to treatment. The FDA has also embraced expedited approval mechanisms (like Fast Track and Breakthrough Therapy designations) which have led to rare diseases comprising over half of new drug approvals in recent years, showing a commitment to speed innovation without compromising safety. Additionally, the NIH has been a major force in rare disease research, funding critical studies and working closely with patient groups to advance scientific discovery. Initiatives like the Rare Diseases Clinical Research Network (RDCRN) now support research on over 200 rare diseases across 20+ consortia in partnership with 170 patient advocacy groups
(rarediseasesnetwork.org), and NIH’s Therapeutics for Rare and Neglected Diseases (TRND) program has helped bridge early research to the clinic – even contributing to FDA approvals such as a recent gene therapy for AADC deficiency and a new Duchenne muscular dystrophy treatment. These concrete efforts by FDA and NIH have measurably accelerated orphan drug development and set benchmarks for the world.
Building on Leadership in Rare Disease Research
With over 12,000 unique rare diseases and more than 20 million Americans living with a rare disease, continued advancements in research and treatment remain a priority. The U.S. has become a global leader in translating scientific discovery into actionable therapies, and the partnerships between patient groups, researchers, and regulators have played a significant role in this progress. Many breakthroughs have emerged from patient-driven initiatives that shape research priorities, advocate for policy changes, and directly fund early-stage drug development. For example, the Cystic Fibrosis Foundation’s venture philanthropy investment (about $150 million) in drug development led to the breakthrough therapy ivacaftor (Kalydeco) in 2012– a life-changing treatment for cystic fibrosis. A family’s quest to save their children with Pompe disease drove the creation of a biotech startup that ultimately developed Myozyme, the first FDA-approved therapy for Pompe. Even ultra-rare diseases have seen progress through patient-led efforts, as the Progeria Research Foundation – founded by the parents of a child with progeria – spearheaded research and clinical trials that culminated in the first treatment for progeria (lonafarnib) approved in 2020. These examples underscore how empowering patients and caregivers to drive research can yield real treatments for previously neglected conditions.
America’s leadership has also had a global impact. U.S.-driven advancements often set the standard for regulatory science and clinical trial innovation worldwide. Through international collaborations – including partnerships with the European Medicines Agency (EMA) and rare disease organizations across Europe and beyond – the FDA has helped shape a more unified and efficient approach to rare disease research. Initiatives such as the FDA-EMA Orphan Cluster provide a model for how cross-border regulatory cooperation can accelerate drug development. By sharing data and aligning review processes, these collaborations ensure that therapies developed in the U.S. can more rapidly reach patients worldwide, and they encourage other nations to adopt similar high standards for orphan drug approval and access.
The Path Forward: Strengthening Our Global Role
Several areas of focus will ensure continued progress in rare disease drug development. Moving forward, maintaining U.S. leadership will depend on expanding innovation, collaboration, and patient-centric approaches:
- Enhancing Regulatory Innovation: The FDA continues to lead advancements in regulatory science – refining the use of real-world evidence, expanding patient-centered trial designs, and streamlining approval processes without compromising safety. The new FDA Rare Disease Innovation Hub offers opportunities to further optimize and modernize clinical trial approaches. Community efforts like the Haystack Project and the Alliance for Pediatric Inclusion in Research also aim to advance innovative trial methodologies, ensuring that even small patient populations can participate in efficient and effective studies.
- Sustaining Collaboration Between NIH, FDA and Patient Groups: The NIH plays a crucial role in funding foundational research for rare diseases. Strong partnerships between the NIH and patient groups help accelerate the transition from discovery to treatment. Building smoother hand-offs from NIH-backed research programs (such as RDCRN, Undiagnosed Disease Network, or TRND) to the FDA’s regulatory pipeline will further enhance efficiency and prevent lost opportunities, ensuring promising therapies seamlessly move into clinical trials and toward approval.
- Deepening Global Collaboration: Engaging with international partners – particularly the EMA, as well as regulatory agencies in Japan, Canada, and Australia – contributes to more harmonized approaches to orphan drug approval and access. Greater regulatory convergence (for example, aligning trial requirements or recognition of each other’s orphan designations) can avoid duplication of effort and speed up global availability of treatments. By strengthening these cross-border collaborations, the U.S. helps ensure that innovations reach patients worldwide and sets the stage for a truly global rare disease strategy.
- Empowering the Patient Community: Rare disease patients and advocacy groups remain central to shaping research priorities and trial designs. Their involvement ensures that patient needs drive continued progress in drug development. Expanding support for patient-led registries, natural history studies, and patient-focused drug development meetings allows regulators and researchers to better understand each condition’s impact. This empowerment of the patient community will continue to yield insights that make therapies more effective and aligned with real-world needs.
- Streamlining Approval Processes: A key next step is working to modify the drug approval process for greater efficiency and shorter timeframes, which can reduce development costs and improve accessibility of new treatments. Efforts are underway to simplify and modernize every stage of drug development – from smarter clinical trial designs (such as platform trials or use of surrogate endpoints) to rolling submissions and expedited review programs. By further shortening review times and eliminating unnecessary hurdles (while maintaining high safety standards), the FDA can help lower the cost of bringing an orphan drug to market. In turn, this may encourage more investment in rare diseases and potentially improve patients’ access to life-saving therapies sooner.
America’s commitment to rare disease innovation has been a beacon of hope for millions. By expanding collaboration, maintaining regulatory excellence, and championing patient-driven innovation, the United States will continue to set the global standard for rare disease drug development – benefiting patients both domestically and across the globe, now and in the future.
