Will rare disease research flourish under the new administration?

The Rise and Challenges of Rare Disease Research in the US

In 2024, a significant milestone was reached in the field of rare disease research: 50% of the novel drugs approved by the FDA had an orphan drug designation. Over the past two decades, this area of medicine has seen exponential growth, enabling innovative biotech companies to develop robust pipelines and attract acquisition interest. However, recent federal funding cuts and a slowdown in legislative processes have sparked concerns among researchers, patient advocates, and biotechs about the sustainability of this progress.

The spotlight on rare disease research has been intensified by the success of several biotechs that have transitioned into major players with groundbreaking product launches. This momentum has been supported by regulatory frameworks in both the US and Europe, which offer incentives to drive innovation. A key initiative in this space is the FDA’s Rare Disease Innovation Hub, launched in July 2024. Designed to engage directly with the rare disease community, the Hub aims to support orphan drug research and foster collaboration across various stakeholders.

Initially, the Hub was co-led by Dr. Patrizia Cavazzoni from the Center for Drug Evaluation and Research (CDER) and Dr. Peter Marks from the Center for Biologics Evaluation and Research (CBER). In November, Amy Comstock was appointed as Director of Strategic Coalitions for the Hub. Since then, the leadership landscape has shifted significantly. Cavazzoni left the FDA to join Pfizer as a chief medical officer, while Marks resigned and publicly criticized Robert Kennedy Jr., citing the need for a “subservient confirmation of his misinformation and lies.”

At the BIO International Convention in Boston, Comstock reiterated the Hub’s commitment to rare disease research and encouraged the rare disease community to build stronger networks. Despite these efforts, the Hub has been operating with borrowed resources from CDER and CBER, as it lacks a dedicated budget in the 2025 fiscal plan. Comstock emphasized that without a comprehensive budget, the Hub may struggle to achieve its intended goals.

One of the Hub’s notable achievements is the establishment of the Rare Disease Innovation Science and Exploration (RISE) workshop series. These workshops aim to address critical issues in rare disease research, such as alternative trial designs for small populations. The first RISE workshop, scheduled for September, will focus on control arms in clinical trials, including historical controls and registries. The discussions will involve patient advocates, biotechs, and disease organizations, with the goal of producing a report that could inform future guidance documents.

The Hub’s unique structure allows it to engage closely with the rare disease community without conflicts of interest, as it does not participate in the drug review process. The ultimate goal is to consolidate institutional knowledge from various agencies to streamline the drug approval process. However, some of the Hub’s educational initiatives, such as materials on grant opportunities and advocacy resources, are currently on hold due to resource constraints.

Policy Challenges and Financial Incentives

A key driver of rare disease research has been financial incentives like the Priority Review Voucher (PRV) program. This program offers expedited approvals for therapies addressing unmet needs, such as rare pediatric diseases, and provides a voucher that can be sold for cash. However, the PRV program for rare pediatric diseases is set to expire in September 2026, raising concerns about its renewal. Health economist David Ridley noted that while the program is likely to be reauthorized, the uncertainty could slow down drug development for several years.

Patient advocates, including Karin Hoelzer from the Biotechnology Innovation Organization (BIO), have expressed worries about the impact of policy changes on rare disease research. The Orphan Cures Act, included in the One Big Beautiful Bill signed into law on July 4, addresses some of these concerns by excluding orphan drugs with multiple indications from Medicare price negotiations, provided the additional indications are for rare diseases.

Navigating Uncertainty and Future Prospects

Despite the challenges, there is cautious optimism about the future of rare disease research. Recent high-profile cases, such as KalVista Pharmaceuticals’ sebetralstat, highlight the complexities of navigating the FDA’s workload and resource limitations. While the agency claims it remains on track to meet its targets, some reports suggest internal pressures to delay approvals.

In a public roundtable focused on cell and gene therapies, Robert Kennedy Jr. emphasized the need to accelerate approvals for rare disease treatments, aiming to position the US as a global hub for biotechnology innovation. As the field continues to evolve, the collaboration between advocates, researchers, and policymakers will be crucial in sustaining the progress made over the past few decades.