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

Area of Science:

• Pharmacology and Drug Development
• Rare Diseases and Orphan Drugs
• Regulatory Science

Background:

• FDA Expedited Program Designations (EPDs) aim to accelerate the development of treatments for serious conditions with unmet medical needs.
• Pulmonary Arterial Hypertension (PAH) is a rare disease with over 10 FDA-approved therapies.
• Understanding the utilization of EPDs in PAH drug development is crucial for future therapeutic advancements.

Purpose of the Study:

• To investigate the landscape of FDA Expedited Program Designations (EPDs) for FDA-approved Pulmonary Arterial Hypertension (PAH) therapies.
• To inform future drug development strategies for rare diseases like PAH by analyzing existing EPDs.
• To identify patterns and gaps in the application and approval of EPDs for PAH treatments.

Main Methods:

• Manual review of publicly available FDA Action Packages (APs) for 10 FDA-approved PAH treatments.
• Data extraction focused on information related to Expedited Program Designations (EPDs).
• Absence of documentation supporting EPD requests or reviews was noted.

Main Results:

• Only ambrisentan received Fast Track Designation; no Breakthrough Designations were identified.
• Bosentan and treprostinil were granted Accelerated Approval Designations.
• Ambrisentan, sildenafil, riociguat, epoprostenol, iloprost, and treprostinil received Priority Review Designations. All but sildenafil received Orphan Drug Designation.

Conclusions:

• Drug developers for PAH should consider novel endpoints and biological mechanisms, and differentiate on safety.
• Early engagement with the FDA (pre-first-in-human) is recommended to align data requirements for securing designations.
• Strategies to increase the probability of obtaining Fast Track or Breakthrough Designations are needed.