United Thera's oral PAH drug treprostinil fails in Ph III study

US biotech firm United Therapeutics (Nasdaq: UTHR) says that preliminary results from its FREEDOM-C(2) Phase III trial of treprostinil diethanolamine (oral treprostinil), an investigational sustained-release oral formulation of treprostinil, a stable synthetic form of prostacyclin, in patients with pulmonary arterial hypertension (PAH), did not achieve statistical significance for the primary endpoint, six-minute walk distance (6MWD) at Week 16. Treprostinil is already marketed in injectable form under the trade name Remodulin and as an inhaled therapy at Tyvaso for the treatment of PAH.

The FREEDOM-C(2) trial was a randomized, double-blind, placebo-controlled trial of patients with PAH, a chronic, life-threatening illness. The study population consisted of 310 patients who were optimized on an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, or both. In addition to one of these oral therapy regimens, patients were administered oral treprostinil or placebo twice daily with the dose titrated (increased to tolerability) over the 16-week trial. The majority (~73%) of patients were World Health Organization (WHO) Class III patients of varied etiologies, including idiopathic or familial PAH (~65%), collagen vascular disease associated PAH (~31%), and PAH associated with HIV or other associated conditions (~3%). Mean baseline walk distance was approximately 333 meters.

The primary efficacy endpoint of the trial was the median change in 6MWD at 16 weeks relative to baseline. With regard to the primary efficacy results, the placebo-corrected median change in 6MWD at Week 16 was 10 meters (p=0.089, Hodges-Lehmann estimate and non-parametric analysis of covariance in accordance with the trial's pre-specified statistical analysis plan).