SILVER SPRING, Md., June 30 United TherapeuticsCorporation (Nasdaq: UTHR) and its wholly-owned subsidiary, Lung Rx, Inc.,announced today the submission of a New Drug Application (NDA) to the U.S.Food and Drug Administration (FDA) for marketing approval of an inhaledformulation of treprostinil (ITRE) for the treatment of pulmonary arterialhypertension (PAH), a chronic, life-threatening disease. The submissionstarts a 60-day period during which the FDA will examine the application forcompleteness. If the FDA accepts the ITRE NDA for review, then it is expectedto be subject to the standard 10- to 12-month review period before an actionletter is issued.
"We believe that an inhaled formulation of treprostinil will be a verydesirable option for PAH patients," said Martine Rothblatt, Ph.D., UnitedTherapeutics' Chairman and Chief Executive Officer. "The completion of theNDA filing is a huge milestone in United Therapeutics' quest to develop asmany formulations of treprostinil as possible to create better, moreconvenient therapies to treat the debilitating effects of PAH along the fullspectrum of the disease."
The ITRE NDA is principally supported by data from the TRIUMPH-1 Phase IIIclinical trial.
TRIUMPH-1 (TReprostinil Sodium Inhalation Used in the Management ofPulmonary Arterial Hypertension), was a randomized, double-blind, placebo-controlled trial of patients with PAH. ITRE is prepared once per day andadministered in four daily inhalation sessions using the NEBU-TEC Optineb(TM)ultrasonic nebulizer, with each inhalation session taking approximately 1-2minutes.
The TRIUMPH-1 clinical trial is one of the first pivotal trials to assessthe incremental benefit of an add-on therapy in PAH patients who are alreadyreceiving an approved background therapy. The study population consisted of235 patients who were optimized on an approved oral therapy for PAH, eitherbosentan (Tracleer(R)), an endothelin receptor antagonist, or sildenafil(Revatio(R)), a phosphodiesterase-5 inhibitor. The majority of patients wereNew York Heart Association (NYHA) Class III (~98%) of varied etiologies,including idiopathic or familial PAH (~60%), collagen vascular diseaseassociated PAH (~30%), and PAH associated with HIV, anorexigens or otherassociated conditions (~10%).
The primary efficacy endpoint of the TRIUMPH-1 clinical trial was thechange in six-minute walk (6MW) distance at 12 weeks measured at peakexposure, defined by the trial protocol as 10-60 minutes after administrationof ITRE relative to baseline. Analysis of the TRIUMPH-1 clinical trialresults confirmed an improvement in median 6MW distance of approximately 20meters (p<0.0005 at peak exposure, Hodges-Lehmann estimate and non-parametricanalysis of covariance in accordance with the trial's pre-specifiedstatistical analysis plan), in patients receiving ITRE as compared to patientsreceiving only background therapy. In addition, the 6MW distance at week 12relative to baseline at trough exposure was also significantly improved, withan estimated treatment effect of approximately 14 meters (p<0.007). Secondaryendpoints related to quality of life and change in NT pro-BNP, a plasmabiomarker of cardiac function, were also significantly improved in the ITREgroup as compared to the group receiving only background therapy (p<0.05).Other secondary efficacy measures, including change in Borg Dyspnea Score(shortness of breath test), NYHA functional class, signs and symptoms score,and time to clinical worsening, were not significantly different between theITRE and background therapy only groups. Safety findings were typically thoseassociated with the well-known vasodilatory side effects of prostacyclin andits analogs (e.g., headache, nausea, dizziness, flushing) and those commonlyassociated with the inhalation route of administration (e.g., cough and throatirritation). These side