Contributions of the Orphan Drug Act: Agents for solid organ transplantation

Contributions of the Orphan Drug Act: Agents for solid organ transplantation Christopher R Ensor, PharmD, Timothy R Cote, MD, MPH, Lili A Barouch MD

Purpose: The Orphan Drug Act (ODA) of 1983 applies to the development of therapies for solid organ transplantations because are considered rare by definition (<200,000 patients per year). The ODA has worked impressively well to incentivize drug development in rare diseases and conditions, including solid organ transplantation (SOT).  We sought to characterize the impact of the ODA on the development and advancement of agents for SOT.

Methods: We used Food and Drug Administration data from the publically available Orphan Drug Product Designation Database to identify orphan designations and approvals for SOT therapies. We examined records from January 1, 1983 until December 31, 2011 and described temporal trends. We classified SOT therapies for peri- or post-transplant use. Peri-transplant agents were subdivided into (1) induction or rescue drugs, (2) drugs for prevention of primary graft dysfunction, and (3) preservation or procurement agents/solutions. Post-transplant agents were subdivided into (1) maintenance anti-rejection therapies, (2) antivirals, or (3) diagnostic agents.  All statistical comparisons were made with Poisson (log-linear) regression and p < 0.05 was considered statistically significant.

Results: We found 45 designated products; 20 (44%) of which are fully marketed.  Comparing the periods 1986-90 to 2006-10, designations and market approvals have progressively increased 5- and 8-fold, respectively. Year-by-year analysis of trends demonstrated a statistically significant increase in SOT designations (p=0.003) and a strong trend toward statistical significance for increased market approvals (p=0.09).

Conclusions: Transplant medicine is unique, and the ability to develop new therapies for SOT patients has been greatly magnified by the orphan designation process. Key approvals have been pivotal in making available drugs with new mechanisms of action that, in several cases, have revolutionized medical therapy for transplant patients.