United Therapeutics Corporation (NASDAQ: UTHR) today announced that the independent data monitoring committee (DMC) for the FREEDOM-EV study of Orenitram (treprostinil) extended-release tablets had completed a pre-specified interim safety and efficacy analysis. The DMC did not identify any new safety concerns associated with Orenitram therapy, and recommended that the trial be continued as planned without modification.
FREEDOM-EV is a Phase 3, international, multi-center, randomized, double-blind, placebo-controlled, clinical worsening study of Orenitram in patients with pulmonary arterial hypertension (PAH) receiving background oral monotherapy study (a phosphodiesterase type 5 inhibitor or an endothelin receptor antagonist). In accordance with the study protocol and DMC charter, previous interim safety analyses were performed at scheduled intervals throughout the study and this interim safety and efficacy analysis was performed after approximately 75% of the target 205 adjudicated clinical worsening (morbidity or mortality) events occurred within the study. United Therapeutics is intentionally blinded to the interim analysis data and will remain blinded to results of the study until after the study is completed.
The threshold for stopping the trial early for overwhelming efficacy was intentionally set high with the understanding that a more robust result, based on a larger number of clinical worsening (morbidity or mortality) events, could be obtained by the study continuing to completion.
The DMC's recommendation to continue as planned reflects its review of all available safety and efficacy data, and was made independently. Neither United Therapeutics nor the U.S. Food and Drug Administration (FDA) has reviewed the interim clinical trial results and neither participated in the DMC's closed session deliberation.
"We had stringent criteria for this interim analysis, and look forward to receiving the full results of the FREEDOM-EV study during the second half of 2018," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "We remain optimistic that the FREEDOM-EV study is positioned for success based on our extensive review of the existing and continually increasing body of data from clinical and real-world evidence studies, and we are preparing for the study's conclusion in accordance with its statistical analysis plan."
Orenitram is an extended-release, oral tablet form of treprostinil, which was launched commercially in the United States during the second quarter of 2014. Orenitram is the only FDA approved, orally administered prostacyclin analogue, and is the only oral PAH prostacyclin class therapy approved in the United States that is titratable to tolerability, without a dose ceiling. Orenitram was approved by the FDA in December 2013 for treatment of PAH patients to improve exercise capacity. Orenitram is not approved in major markets outside the United States. The primary study that established efficacy included predominately patients with functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%).