Phase 3 Data Points to Treprostinil as a Treatment for Pulmonary Hypertension
JUNE 25, 2020
Steven D. Nathan, MD
On June 17, the United Therapeutics Corporation announced positive data from the INCREASE study showing treprostinil inhalation solution is effective treating patients with pulmonary hypertension associated with interstitial lung disease.
In the phase 3, multicenter, randomized, double-blinded, placebo-controlled, 16-week, parallel group study, the investigators examined 326 patients who received either the study drug or a placebo.
The data was presented virtually at the American Thoracic Society (ATS) 2020 Virtual Sessions this week by investigator Steven D. Nathan, MD, professor of medicine at Virginia Commonwealth University Inova Campus.
Treprostinil is a prescription medicine for adult patients with pulmonary arterial hypertension. The drug ultimately improves the patient’s ability to exercise 4 hours after administration.
The investigators sought primary endpoints of the evaluation of changes in the six-minute walk distance (6MWD) test measured at peak exposure from baseline to week 16.
They also sought secondary objectives of the change in plasma concentration of N-terminal pro-brain natriuretic peptide (NT–proBNP) from Baseline to Week 16 and the time to clinical worsening calculated as the time from randomization until either hospitalization due to a cardiopulmonary indication, decrease in 6MWD >15% from baseline directly related to disease under study, at 2 consecutive visits, and at least 24 hours apart, death (all causes), or lung transplantation is met.
Other secondary endpoints included the change in peak 6MWD from baseline to week 12 and the change in trough 6MWD from baseline to week 15.
The investigators also sought exploratory objectives evaluating changes in peak the six-minute walk distance at week 4 and 8, as well as changes in quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ), and change in distance saturation product (DSP).
Researchers previously showed that treprostinil increased the six-minute walk distance by 21 meters when compared to placebo (P = 0.0043, Hodges-Lehmann estimate) after 16 weeks.
The investigators identified treatment benefits across a number of key subgroups, including etiology of PH-ILD, disease severity, age, gender, baseline hemodynamics, and dose.
They also discovered significant improvements in all of the study’s secondary endpoints, including reduction in the cardiac biomarker NT-proBNP, time to first clinical worsening event, change in peak 6MWDF at week 12, and change in trough 6MWD at week 15.
Treatment with treprostinil of up to 12 breaths per session four-times per data was well-tolerated, with a safety profile consistent with previous studies testing the treatment in pulmonary arterial hypertension and known prostacyclin-related adverse events.
Some common side effects include cough, headache, throat irritation and pain, nauseam reddening of the face and neck, fainting or loss of consciousness, dizziness, and diarrhea.
Some of the serious side effects include symptomatic hypotension and bleeding.
United Therapeutics has submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) seeking to revise the label on Tyvaso label to reflect the outcome of the recent study.
The investigators also plan on further exploratory analysis on biomarkers and pharmacogenomics from the study.