United Therapeutics’ Orenitram faces onerous task of convincing pulmonologists to pick drug over J&J's Uptravi - experts
United Therapeutics’ (NASDAQ:UTHR) Phase III FREEDOM-EV design and resulting label for Orenitram (oral treprostinil) allowing only one background therapy will significantly hamper uptake in pulmonary arterial hypertension (PAH), experts said. Dosing and titration challenges compared to competitors will also likely deter widespread use, they added.
Orenitram was originally approved in 2013, based on FREEDOM-M (NCT00325403), which had six-minute walking distance (6MWD) as a primary endpoint. While FREEDOM-EV (NCT01560624) was initiated in July 2012 -- to prove efficacy in a thrice-daily regimen on a single background therapy -- experts said subsequent positive studies from competitors with the more robust morbidity/mortality event-driven endpoints were driving preference, such as Johnson and Johnson’s (NYSE:JNJ) Uptravi (selexipag) approved in 2015.
Even if the FREEDOM-EV study has a positive result, it would likely not be enough to push pulmonologists to adopt Orenitram over Uptravi, because of FREEDOM-EV’s study design allowing only one background therapy, which will likely be on the label. This would be unfavorable, experts said, as standard of care (SOC) now dictates the use of a combination of a PDE5 inhibitor with an endothelin receptor antagonist (ERA) as background therapy before a prostacyclin analog. Furthermore, Uptravi has cemented its position as a prostacyclin agent of choice with robust data via its GRIPHON study (NCT01106014), while Orenitram has had two failed Phase III trials and one with a clinically insignificant positive result, they noted.