Pulmonary Arterial Hypertension: A Case Study in FDA Expedited Program Designations

Abstract

Background: FDA expedited program designations (EPDs) are intended to facilitate drug development for serious conditions with an unmet medical need. There are over 10 FDA-approved therapies for the rare disease pulmonary arterial hypertension (PAH). This work investigates the landscape of EPDs in the context of FDA-approved PAH therapies in order to inform on future drug development. Methods: The publicly available FDA Action Package (AP) was manually culled for information related to EPDs for 10 FDA-approved treatments for PAH. Documentation supporting the EPD request and/or its review (including potential rejection) was not found during the data cull. Results: This investigation finds that (1) only ambrisentan received the Fast Track Designation; (2) no Breakthrough Designations were elucidated; (3) bosentan and treprostinil received Accelerated Approval Designations, and (4) ambrisentan, sildenafil, riociguat, epoprostenol, iloprost, and treprostinil received Priority Review Designations. All therapies (except sildenafil) received an Orphan Drug Designation. Conclusion: Based on these results, it is recommended that drug developers be encouraged to revisit traditional endpoint measures, explore novel biological mechanisms, and/or effectively differentiate in other dimensions (eg, safety). Developers should also consider engaging the FDA early in development (ideally prior to first-in-human) to agree on the kind and amount of data to meet the statutory bar with the intention of increasing the probability of securing a Fast Track or Breakthrough Designation.