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

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.