Every year on February 28 we observe Rare Disease Day, a moment to recognize those living with rare diseases around the world and to highlight the scientists, patients, caregivers and biopharmaceutical researchers working to transform lives. Rare diseases may be individually uncommon, but collectively they affect an estimated 25–30 million Americans and hundreds of millions globally.
What is a rare disease?
The Orphan Drug Act of 1983 (ODA) generally defines a rare disease as a condition that affects fewer than 200,000 people nationally. There are approximately 7,000 known rare diseases, ranging from genetic disorders and metabolic conditions to rare cancers and immunological diseases. Many have severe, life-threatening symptoms, and only about 5% of known rare diseases have an approved treatment option.
Developing treatment is challenging
Drug development is a lengthy and complex process, and rare diseases pose unique hurdles:
- Small patient populations: Recruiting enough participants for clinical trials can be extremely difficult when only a few hundred or thousand people worldwide have a condition.
- Treatment complexity: Many rare diseases are genetic in origin and require cutting-edge biomedical innovation and new scientific approaches to develop treatments. With some rare diseases, there is limited understanding of the disease's progression and how the disease affects a patient, which imposes unique complexities for developing treatments.
- Economic uncertainty: Because of the limited market size due to small patient populations, it can be difficult to encourage the immense investments necessary to advance rare disease research and development.
- Regulatory challenges: Standard trial designs are often not feasible and endpoints are not always fully developed. As a result, companies must explore innovative approaches and trial designs that regulators will consider for review.
Innovation is advancing
The ODA created several incentives to spur rare disease research and development, and these have helped fuel tremendous progress to address unmet medical need. The biopharmaceutical industry is investing in research, resulting in new medicines for rare diseases every year:
- In the decade before the ODA was passed, only 10 drugs for rare diseases were brought to market. Over the past four decades since the ODA, the FDA has granted orphan drug designation to thousands of molecules and therapies, leading to about 800 approved rare disease medicines.
- In 2025, approximately 50% of new drug approvals were for rare diseases.
These medicines aren’t just statistics — they represent new and additional options for patients with conditions that once had no therapy.
Cutting-edge technologies drive progress
Transformative treatments like gene therapy and precision medicine are becoming reality. With 438 cell and gene therapies in development in the U.S. at the end of 2025, these targeted treatments are now moving from research labs into clinical trials and eventually into doctors’ offices, offering potential treatments for many rare diseases that arise from specific genetic defects.
PhRMA member companies are investing not only in rare disease research and development but domestic manufacturing of rare disease treatments as well — accelerating development and delivery of life-saving treatments while also creating high-skilled jobs and strengthening the U.S. drug development ecosystem.
Looking ahead: Innovation built on collaboration
Rare Disease Day is a reminder that though we’ve seen major achievements in rare disease drug development, there are still millions of patients with no treatment options. The path forward depends on continued collaboration among industry, patients, policymakers and researchers to remove obstacles and accelerate meaningful breakthroughs.
Progress also requires sustained support for policies that fuel investment while ensuring patients can access new therapies. The recent enactment of the Orphan Cures Act, which helped address the disincentives for orphan drug development that were implemented as part of the Inflation Reduction Act as originally enacted, represents an important step forward in ensuring future progress for patients with rare diseases.
PhRMA member companies remain committed to bringing more life-changing treatments to those who need them most. Learn more at PhRMA.org/RareDiseases.
Mike Ybarra
Michael Ybarra, M.D., is an emergency physician and Chief Medical Officer at PhRMA. He also serves as Senior Vice President in Advocacy and Strategic Alliances. In these roles, he leads PhRMA’s stakeholder engagement and strategic partnerships on federal and international health policy issues. He is PhRMA’s liaison representative to the Advisory Committee on Immunization Practices and is the co-convener of PhRMA’s R&D Leadership Forum. Dr. Ybarra continues to see patients clinically in the emergency department at MedStar Georgetown University Hospital.
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Mike Ybarra