RESULTS

TYVASO® increased exercise capacity to help patients with PH-ILD walk farther1,2

At week 16 in the Hodges-Lehmann analysis, patients who took TYVASO had a placebo-corrected median difference in peak 6MWD of 21 m1

Change in 6MWD (m) from baseline through week 161,3*†‡

Hodges-Lehmann placebo-corrected median difference.

Patients who took TYVASO saw improvement in 6MWD starting as early as week 4 and reached statistical significance by week 12.1

TYVASO improved 6MWD across a range of PH-ILD subgroups.

*Weeks 4 and 8 were exploratory endpoints and weeks 12 and 15 were secondary endpoints.3

P values were obtained from nonparametric ANCOVA adjusted for baseline 6MWD category.3

At week 15 (trough), patients who took TYVASO had a placebo-corrected median difference in 6MWD of 15 m (P=0.04).3

§Benefits were observed across several subgroups, including etiology of PH-ILD, disease severity (measured by baseline 6MWD), age, sex, baseline hemodynamics, and dose group.1

A sensitivity analysis supports the finding that patients with PH-ILD who took TYVASO walked farther2,4

At week 16 in the MMRM analysis, patients who took TYVASO had a placebo-corrected difference in peak 6MWD of 31 m2

Change in peak 6MWD (m) from baseline through week 162,4||¶

INCREASE study change in peak 6MWD from baseline through week 16.INCREASE study change in peak 6MWD from baseline through week 16.

MMRM placebo-corrected LS mean difference.

MMRM analysis was a prespecified sensitivity analysis for the primary endpoint.4

MMRM uses all available data at all timepoints and does not require imputation of individual missing data points. In Hodges-Lehmann methodology, imputed walk of 0 m was assigned for death, clinical worsening event, and too ill to perform 6MWT. The last observation was carried forward for all other reasons.3

||LS mean, P values, and estimated difference were from the MMRM with the change from baseline in peak 6MWD as the dependent variable; treatment, week, and treatment-by-week interaction as the fixed effects; baseline 6MWD as the covariate; and subject as the random effect.4

At week 15 (trough), patients who took TYVASO had a placebo-corrected LS mean difference in 6MWD of 22 m (P=0.004).2

During the 16-week study, TYVASO reduced the risk of a clinical worsening event by 39%1,2**††

Time to first clinical worsening event1,3

TYVASO showed a 39% reduction in the risk of clinical worsening during the INCREASE studyTYVASO showed a 39% reduction in the risk of clinical worsening during the INCREASE study

Clinical worsening events included a hospitalization due to a cardiopulmonary indication (11% TYVASO vs 14.7% placebo); a decrease in 6MWD >15% from baseline (8% TYVASO vs 16% placebo); death–all causes (2.5% TYVASO vs 2.5% placebo); or lung transplantation (1.2% TYVASO vs 0% placebo).1,2‡‡

**Overall, incidence of any clinical worsening event was 22.7% for patients who took TYVASO vs 33.1% for those who took placebo (P=0.04).2

††Patients who discontinued from the study early had their time to clinical worsening censored at their last visit. Patients who did not experience a clinical worsening event had their time to clinical worsening censored at the study termination date.3

‡‡P value was calculated with log-rank test stratified by baseline 6MWD category.3

§§HR, 95% CI, and P value were calculated with proportional hazards model with treatment and baseline 6MWD (continuous) as explanatory variables.3

TYVASO reduced NT-proBNP, a biomarker associated with RV dysfunction2,5

At week 16, TYVASO resulted in a 15% reduction in NT-proBNP compared with a 46% increase for placebo (P<0.001)2|| ||

NT-proBNP: change from baseline (%)2,4

NT-proBNP reduction during INCREASE trialNT-proBNP reduction during INCREASE trial

The role of NT-proBNP in PH-ILD and the clinical significance of changes associated with therapy are unknown.

|| ||P value was obtained from the MMRM analysis with the change from baseline in log-transformed NT-proBNP as the dependent variable; treatment, week, and treatment-by-week interaction as the fixed effects; and log-transformed baseline NT-proBNP as the covariate.4

NOTE: Elevated levels of BNP and NT-proBNP are biomarkers that are indicative of RV dysfunction.5

6MWD=6-minute walk distance; 6MWT=6-minute walk test; ANCOVA=analysis of covariance; CI=confidence interval; HR=hazard ratio; LS=least squares; MMRM=mixed-effect model repeat measurement; NT-proBNP=N-terminal pro−B-type natriuretic peptide; PH-ILD=pulmonary hypertension associated with interstitial lung disease; RV=right ventricular.