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Maximizing The Next 40 Years of The Orphan Drug Act 

This article is based on the session titled, “Sustainability of Rare Disease Drug Development,” at the DIA 2024 Global Annual Meeting, in San Diego, June 2024. Many thanks to the presenters: Darcy Frear (Bridgebio), Katherine Donigan (Sarepta), Karin Hoelzer (NORD), Patroula Smpokou (FDA), and Julia Tierney (FDA) for their valuable insights. This translation and the recommendations captured within is the author’s rendering of their points and should not be taken as exact quotations. 

Increasing Orphan Disease Drug Approvals: Strategies for Sustainability 

The passing of the Orphan Drug Act (ODA) in the U.S. in 1983 was a critical point for rare disease drug development, offering financial incentives through its Orphan Drug Designation Program and enabling scientific advances and approvals for rare disease drugs. Before the ODA was signed into law, approximately two drugs per year had been approved by the U.S. Food and Drug Administration (FDA) for rare diseases. Now, with 40 years since the ODA, hundreds of orphan drugs have been approved for use in the many diseases and conditions that are considered rare. In the past four decades, over 6,000 orphan drug designations were granted, and of those, 1,079 represent the development for rare diseases.1 

While the approval rate of orphan drugs has seen a significant increase, maintaining and further enhancing this trend requires strategic action. Current incentives such as grants, tax credits, market exclusivity, and the FDA’s Fast Track designation play crucial roles in the development over the next 40 years. 

Key Areas for Sustaining Orphan Disease Drug Development 

  1. Continuation of Successful Strategies: Accelerated Approval (AA) processes with surrogate endpoints must be sustained. This approach has been vital in bringing treatments to market faster, saving lives in the process. 
  2. Enhanced Collaboration: Increasing scientific discussions with the FDA through smaller working groups can advance the field. Incorporating diverse voices, including perspectives from patient advocacy groups, regulatory, scientific, and sponsors, is essential. 
  3. Policy Shifts: Moving from individual product approvals to advancing entire fields of products is crucial. Pilot programs should transition into full-scale applications, backed by robust policy and guidance documents. 
  4. Learning from the Past: Transparency about what works and what does not work is critical. The complexity of rare and orphan diseases requires a willingness to innovate and adapt based on past experiences. 
  5. Patient-Centric Approaches: Including the patient voice in the development process ensures treatments meet real needs.  

Addressing Obstacles and Leveraging Tools 

Reimbursement and approval obstacles hinder the development and availability of treatments. Utilizing all available tools for development and regulatory oversight, while maintaining flexibility, is vital for navigating uncharted territories. 

AA remains a cornerstone for bringing life-saving drugs to market. Contrary to misconceptions, AA still maintains rigorous scientific and regulatory standards. Future policies must continue to protect and optimize this pathway. 

Opportunities in Orphan Disease Drug Development 

  1. Collaboration with Regulatory Bodies: Enhanced cooperation between agencies like the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) is crucial. Clear, adaptable rules are needed to incorporate new technologies effectively. 
  2. Early and Frequent FDA Engagement: Sponsors should engage with the FDA early and consistently throughout the drug development process. Sharing both successful and failed data can provide valuable insights. 
  3. Legislative Support: Protecting incentives under the Orphan Drug Act and the Inflation Reduction Act is essential. In addition, scaling up FDA pilot programs can address barriers more effectively. For additional insights, read: Rare But Not Forgotten: Opportunities in Rare Disease Drug Development or Preparing Now for the FDA’s START Program.  
  4. Breaking Down Silos: Greater alignment and collaboration within regulatory bodies can streamline rare and orphan disease drug development. Efforts to engage sponsors on efficacy endpoints and biomarkers are ongoing. 

Propelling Development Forward 

Emerging technologies, such as gene editing and next-generation sequencing, hold immense potential. Improved diagnostics and decentralized trial methods, including telehealth and Artificial Intelligence, can enhance patient outcomes and trial efficiency. Expanding platform approaches and manufacturing improvements will also help reduce costs and increase access to treatments. 

Halloran offers expertise in navigating the complex landscape of orphan and rare disease drug designation in regulatory affairs, clinical development, and strategic planning. By leveraging our deep understanding of the regulatory requirements and our proven track record of success, our clients enhance their chances of obtaining rare or orphan disease drug designation efficiently and effectively.  

Choosing Halloran’s experts means process efficiencies coupled with comprehensive support and guidance every step of the way, accelerating the path to market for their unique therapies and fast tracking the timeline for lifesaving treatments. To learn more about how we can help you, contact us.  


  1. Fermaglich LJ, Miller KL. A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act. Orphanet J Rare Dis. 2023 Jun 23;18(1):163. doi: 10.1186/s13023-023-02790-7. PMID: 37353796; PMCID: PMC10290406.