The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Tyvaso® (treprostinil; United Therapeutics) for the treatment of patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability.
The approval was based on data from the multicenter, double-blind, placebo-controlled phase 3 INCREASE study (ClinicalTrials.gov: NCT02630316) that evaluated the efficacy and safety of Tyvaso inhalation solution in 326 adult patients with PH-ILD. The study predominately included patients with etiologies of idiopathic interstitial pneumonia (45%) inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema (25%), and WHO Group 3 connective tissue disease (22%).
Patients were randomly assigned 1:1 to receive either inhaled Tyvaso 0.6mg/mL four times daily or placebo for 16 weeks. The primary endpoint was the change in 6-minute walk distance (6MWD) at peak exposure from baseline to week 16.
Results showed that treatment with Tyvaso was associated with an increase in 6MWD by 21 meters compared with placebo (P =.0043, Hodges-Lehmann estimate). Moreover, the treatment difference in 6MWD was reported to be statistically significant when analyzed using Mixed Model Repeated Measurement (31 meters; P <.001). Additionally, patients treated with Tyvaso achieved the following significant improvements in all secondary endpoints compared with placebo:
- Reduction of 42% in NT-proBNP at week 16 (P <.001);
- Reduction of 39% in the risk of a clinical worsening event (22.7% vs 33.1%, respectively; P =.04);
- Exacerbations of underlying lung disease in 26.4% vs 38.7%, respectively (P =.02); and
- Significant improvements in peak 6MWD at week 12 with Tyvaso vs placebo (31.29 meters; P <.001) and trough 6MWD at week 15 (21.99 meters; P =.005).
The safety profile of Tyvaso was consistent with that seen in previous studies in pulmonary arterial hypertension and with known prostacyclin-related adverse events. The most common treatment-related adverse events included cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea.
Tyvaso is supplied in 2.9mL ampules containing 1.74mg treprostinil per ampule at a concentration of 0.6mg/mL. It is intended for oral inhalation using the Tyvaso Inhalation System, which consists of an ultrasonic, pulsed delivery device and its accessories.
1. United Therapeutics announces FDA approval and launch of Tyvaso® for the treatment of pulmonary hypertension associated with interstitial lung disease. [press release]. Silver Spring, MD and Research Triangle Park, NC: United Therapeutics Corporation; April 1, 2021.
2. United Therapeutics announces New England Journal of Medicine publication of the INCREASE study evaluating Tyvaso® in pulmonary hypertension associated with interstitial lung disease. [press release]. Silver Spring, MD and Research Triangle Park, NC: United Therapeutics Corporation; January 13, 2021.