SILVER SPRING, Md., Nov. 1 United TherapeuticsCorporation (Nasdaq: UTHR) and its wholly-owned subsidiary, Lung Rx, Inc.,announced today the completion of their TRIUMPH-1 Phase 3 trial of Viveta, aninhaled formulation of treprostinil, in pulmonary arterial hypertension (PAH).Preliminary analysis demonstrates that the trial has robustly met its primaryendpoint.
The TRIUMPH-1 (TReprostinil Sodium Inhalation Used in the Management ofPulmonary Arterial Hypertension) trial was a randomized, double-blind,placebo-controlled trial of patients with severe PAH, a chronic, life-threatening illness. The study population consisted of 235 patients who wereoptimized on an approved oral therapy for PAH, either bosentan (Tracleer), anendothelin receptor antagonist, or sildenafil (Revatio), a phosphodiesterase-5inhibitor. In addition to one of these oral therapies, patients wereadministered Viveta or placebo in four daily inhalation sessions with amaximum dose of 45 micrograms per session over the course of the 12-weektrial. The majority (~98%) of patients were New York Heart Association (NYHA)Class III of varied etiologies, including idiopathic or familial PAH (~55%),collagen vascular disease associated PAH (~35%), and PAH associated with HIV,anorexigens or other associated conditions (~10%). Mean baseline walkdistance was approximately 350 meters.
The primary efficacy endpoint of the trial was the change in six-minutewalk (6MW) distance at 12 weeks measured at peak exposure, defined by thetrial protocol as 10-60 minutes after inhalation of Viveta, relative tobaseline. Preliminary analysis of the TRIUMPH-1 results demonstrates animprovement in median 6MW distance by approximately 20 meters (p<0.0006,Hodges-Lehmann estimate and non-parametric analysis of covariance inaccordance with the trial's pre-specified statistical analysis plan), inpatients receiving Viveta as compared to patients receiving placebo.
The trough exposure, defined by the trial protocol as a minimum of fourhours after inhalation of Viveta, for treatment change in 6MW distance at week12 relative to baseline was also significantly improved, with an increase inmedian 6MW distance of approximately 14 meters (p<0.01). Additionally, the6MW distance at week 6 relative to baseline was significantly improved, withan increase in median 6MW distance of approximately 18 meters (p<0.0005).
Preliminary analysis of other secondary efficacy measures, includingchange in Borg Dyspnea Scale rating (shortness of breath test), NYHAfunctional class, time to clinical worsening (as defined by death, transplant,atrial septostomy, hospitalization due to PAH, or initiation of anotherapproved PAH therapy), and the 6MW distance at treatment day 1, did not differsignificantly between the Viveta and placebo groups (p>0.05). Analysis of tworemaining secondary endpoints, quality of life and signs and symptoms ofdisease (composite measure) is ongoing.
Viveta was generally well-tolerated in the trial and adverse eventsappeared to be similar to those previously reported for treprostinil. Themost common adverse events seen in the trial were transient cough, headache,nausea, dizziness and flushing. Detailed analysis of the reported adverseevents is ongoing. All patients in the trial had the option to continuereceiving Viveta in an open-label continuation study after completion of the12-week study period. Of the 212 patients who completed the 12-week studyperiod, approximately 200 patients entered the open-label continuation study.Approximately 160 patients are currently being treated with Viveta, with thelongest duration of treatment exceeding two years.
"I am elated by the success of our TRIUMPH study," said Martine Rothblatt,Ph.D., Chairman and Chief Executive Officer of both United Therapeutics andLung Rx. "Special recognition is owed to the two physicians who urged us todevelop this medicine