Inhaled treprostinil (Tyvaso®) was associated with improved forced vital capacity (FVC), compared to placebo, over 16 weeks in patients with idiopathic pulmonary fibrosis (IPF), a post-hoc analysis found.
“We measured FVC in the INCREASE study as a safety endpoint to make sure treatment with Tyvaso was not exacerbating patients’ underlying lung diseases, said Leigh Peterson, PhD, senior vice president, product development of United Therapeutics. “What we found was quite to the contrary, as we saw improvement in lung function among several subgroups including those with PH associated with IPF.”
Gil Golden, MD, PhD, chief medical officer of United Therapeutics, said “this analysis is exciting because rather than slowing down the rate of FVC deterioration, Tyvaso improved FVC in the relatively short 16-week duration of the INCREASE study.”
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INCREASE Study Findings
The multicenter, randomized, double-blind, 1:1 placebo-controlled, 16-week study evaluated Tyvaso in 326 adult patients suffering from pulmonary hypertension-idiopathic lung disease (PH-ILD) categorized by the World Health Organization (WHO) as Group 3 . A total of 326 patients participated at 93 different centers; 163 inhaled Tyvaso 4 times daily, and 163 received a placebo.
The prime efficacy endpoint was the change in six-minute walk distance (6MWD), measured at peak exposure, between baseline and week 16. The results showed that treatment with inhaled Tyvaso was well tolerated and improved 6MWD. The benefits of Tyvaso were observed across various subgroups of interest.
Secondary endpoints included the difference in plasma concentration of the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) noted from baseline to week 16 and time to clinical worsening as measured by various metrics. Results showed significant improvements in each secondary endpoint, including reducing NT-proBNP, reducing the risk of a clinical worsening, and fewer patients having exacerbations of underlying lung disease.
Phase 3 Study Plans
Improved FVC, particularly in IPF patients, is part of the basis of the phase 3 TETON registration study of Tyvaso being conducted by United Therapeutics. The company is seeking to add an IPF indication to Tyvaso’s labeling.
“We are looking to expand on these results in the TETON study, in hopes of demonstrating a label-enabling FVC improvement in patients with IPF,” Dr. Peterson said.
TETON is a 396-patient, multicenter, randomized, double-blind, placebo-controlled trial. The study will evaluate the safety and efficacy of Tyvaso in patients with IPF over 52 weeks. Subjects will be randomly allocated 1:1 to receive inhaled Tyvaso or placebo to investigate FVC, a key prognostic indicator for IPF. The study’s primary endpoint is the change in FVC from baseline at week 52 of treatment.
“If the TETON study supports eventual approval of Tyvaso in patients with IPF, we look forward to providing a new treatment option for these patients with few current treatment options for this life-threatening medical condition,” Dr. Golden said.
United Therapeutics announces The Lancet Respiratory Medicine publication of post-hoc analysis of FVC change from the Tyvaso® INCREASE study News release. United Therapeutics Corporation; June 30, 2021.