United Therapeutics announces NEJM publication of the INCREASE study for Tyvaso in pulmonary hypertension associated with interstitial lung disease.

United Therapeutics Corporation announced that results from the INCREASE clinical study of Tyvaso(treprostinil) Inhalation Solution for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD) have been published online in the New England Journal of Medicine . Results from INCREASE : the largest and most comprehensive completed study of adult patients with PH-ILD, showed that treatment with inhaled Tyvaso was well tolerated and improved the exercise capacity measure of six-minute walk distance (6MWD) by 31 meters relative to placebo at Week 16 (p<0.001) using the mixed model repeated measurement analysis. additionally, patients treated with tyvaso experienced significant improvements in other clinically meaningful outcomes, including a decreased risk of clinical worsening, an improvement in forced vital capacity, and a reduction in exacerbation of underlying lung disease. increase study design and results : the multicenter, randomized, double-blind, placebo-controlled, 16-week, parallel-group increase study evaluated tyvaso in adult patients suffering from world health organization (who) group 3 ph-ild. a total of 326 patients were enrolled at 93 centers and randomized to inhaled tyvaso (n="163)" four times daily or placebo (n="163)." united therapeutics previously announced topline data from increase showing it met all primary and secondary endpoints. the primary efficacy endpoint was the change in six-minute walk distance (6mwd) measured at peak exposure from baseline to week 16. results showed that tyvaso significantly increased 6mwd by 31 meters as analyzed using the mixed model repeated measurement (p><0.001). when analyzed using a pre-specified worst case imputation for missing data and hodges-lehmann estimate, tyvaso improved 6mwd by 21 meters relative to placebo over the same time period (p="0.0043)." the benefits of tyvaso were observed across subgroups, including etiology and severity of ph-ild, age group, gender, baseline hemodynamics, and dose group. secondary endpoints included change in plasma concentration of the cardiac biomarker n-terminal pro-brain natriuretic peptide (nt-probnp) from baseline to week 16; time to clinical worsening as measured by various metrics including hospitalization due to a cardiopulmonary indication, death (all causes) or lung transplantation; change in peak 6mwd from baseline to week 12; and change in trough 6mwd from baseline to week 15. results showed significant improvements in each of the secondary endpoints : i. a 42% reduction in nt-probnp with tyvaso versus placebo at week 16 (p><0.001).ii. a 39% reduction in the risk of a clinical worsening event with tyvaso versus placebo (p="0.04)." 22.7% of patients treated with tyvaso experienced a clinical worsening event versus 33.1% of placebo patients. iii. significantly fewer patients in the treprostinil group than in the placebo group had exacerbations of underlying lung disease (26.4% versus 38.7%, p="0.02)." iv. significant improvements in peak 6mwd at week 12 with tyvaso compared with placebo (31.29 m, p><0.001) and trough 6mwd at week 15 (21.99, p="0.005)." treatment with tyvaso of up to 12 breaths per session, four times daily, was well tolerated. most treatment-related adverse events were mild to moderate in intensity and included cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea, consistent with the existing tyvaso label. the safety profile was similar to previous studies of tyvaso in pulmonary arterial hypertension and known prostacyclin-related adverse events . see- " inhaled treprostinil in pulmonary hypertension due to interstitial lung disease"-aaron waxman, m.d., ph.d., ricardo restrepo-jaramillo, m.d., thenappan thenappan, m.d., et al.-january 13, 2021. doi: 10.1056 nejmoa2008470.>