United Therapeutics (UTHR) Study Update summary

Study overview and design

• TETON-2 was a 597-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 study of nebulized Tyvaso (treprostinil) in idiopathic pulmonary fibrosis (IPF) over 52 weeks across 16 countries outside the US and Canada.

• Patients were randomized 1:1 to Tyvaso or placebo, stratified by background IPF therapy, titrated from 3 to 12 breaths four times daily, with eligibility for open-label extension after 52 weeks.

• Primary endpoint was absolute change in forced vital capacity (FVC) at week 52; secondary endpoints included time to clinical worsening, acute exacerbation, survival, percent-predicted FVC, quality of life (K-BILD), and DLCO.

• Key inclusion: age ≥40, FVC ≥45% predicted, confirmed IPF diagnosis by high-res CT within 12 months, and stable on nintedanib or pirfenidone if used.

• Baseline characteristics were balanced between groups, with mean age ~72 years and similar distribution of background therapies.

Efficacy results

• The study met its primary endpoint, showing a statistically significant placebo-corrected median difference in FVC of 95.6 mL at 52 weeks (95% CI, 52.2–139.0; P<0.0001), with separation of treatment curves as early as week 16.

• Statistically significant improvements were observed in several secondary endpoints, including time to first clinical worsening (HR 0.71, P=0.0190), percent predicted FVC (2.7% difference, P<0.0001), KBILD (2.29 point difference, P=0.0124), and DLCO (1.91% difference, P=0.0416).

• Consistent treatment effect observed across subgroups, including those on background antifibrotic therapy and treatment-naive patients, with ~50 cc loss of lung function in all treated groups.

• Secondary endpoints: 46% relative reduction in acute exacerbation (not statistically significant), 23% relative reduction in mortality (not statistically significant), and significant improvements in quality of life scores.

• Improvement in DLCO and consistent benefit across all subgroups, with higher doses showing greater FVC benefit.

Safety and tolerability

• Inhaled treprostinil was well tolerated, with a safety profile consistent with previous studies and known prostacyclin-related adverse events; most common were cough (48% vs 24% placebo), headache, and diarrhea.

• 91.89% of patients experienced at least one adverse event; 64.8% of treated patients had at least one drug-related adverse event versus 42.4% on placebo.

• Serious adverse events and deaths were similar between groups; 3.4% of patients in the treatment group had AEs leading to death versus 2.0% in placebo.

• Discontinuation rates: 100 of 298 in the treatment arm and 73 in placebo discontinued prematurely, with adverse events and patient decision as main reasons.

• Nebulizer fatigue and mild/moderate cough contributed to discontinuations, but severe cough was rare.