Tyvaso (treprostinil) / United Therapeutics Corporation, MannKind - LARVOL DELTA

Combined results of the TETON-1 and TETON-2 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. (PubMed, Am J Respir Crit Care Med) - P3 | "Inhaled treprostinil slowed the rate of lung function loss, delayed clinical worsening and IPF exacerbations, and demonstrated benefits in DLCO and quality of life over 52 weeks. The results support the use of inhaled treprostinil in patients with IPF.(Funded by United Therapeutics Corp; ClinicalTrials.gov number, NCT04708782 for TETON-1 and NCT05255991 for TETON-2)."

Journal • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Tyvaso: Newly added patent in Orange Book (Orange Book) - Expiry on Mar 14, 2034

Patent • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Respiratory Diseases

United Therapeutics Corporation Announces FDA Acceptance of Supplemental New Drug Application for Nebulized Tyvaso to Treat Idiopathic Pulmonary Fibrosis (United Therapeutics Press Release) - "United Therapeutics anticipates the agency's review to be complete in late April 2027. Nebulized Tyvaso has not been approved by the FDA for IPF and remains investigational for this indication....The filing was based on positive results from the phase 3 TETON-1 and TETON-2 studies."

FDA filing • PDUFA • Idiopathic Pulmonary Fibrosis

United Therapeutics is currently seeking priority review of an sNDA submitted to the FDA in June 2026 to add IPF to the labeled indications for nebulized Tyvaso based on data from the TETON-1 and TETON-2 studies. (United Therapeutics Press Release)

FDA filing • Idiopathic Pulmonary Fibrosis

United Therapeutics Corporation...announced full enrollment of its TETON-PPF study evaluating the use of Tyvaso (treprostinil) inhalation solution (nebulized Tyvaso) for the treatment of progressive pulmonary fibrosis (PPF). The TETON-PPF study enrolled 754 patients. (United Therapeutics Press Release) - "If the TETON-PPF trial is successful, United Therapeutics intends to use the data from the study to support a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) to add PPF to the labeled indications for nebulized Tyvaso. Nebulized Tyvaso has not been approved by the FDA for PPF and remains investigational for this indication.....topline data is expected in the second half of 2027."

Enrollment closed • P3 data: top line • Fibrosis • Immunology

Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary Fibrosis. (PubMed, CHEST Pulm) - P3 | "Background use of pirfenidone or nintedanib is allowed...When completed, TETON-PPF will confirm whether inhaled treprostinil is safe and effective for the treatment of PPF. ClinicalTrials.gov; No.: NCT05943535; URL: www.clinicaltrials.gov."

Clinical • Journal • P3 data • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

TETON-OLE: Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease (clinicaltrials.gov) - P3 | N=1850 | Enrolling by invitation | Sponsor: United Therapeutics | Trial completion date: Jun 2026 ➔ Dec 2029 | Trial primary completion date: Jun 2026 ➔ Dec 2029

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Real-World Use of Tyvaso DPI in Patients with PH-ILD using de-identified US Electronic Health Records (WASOG 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Interstitial Lung Disease

United Therapeutics Corporation Announces TETON-1 Study of Tyvaso Published in The New England Journal of Medicine and Presented at ATS 2026 (Businesswire) - "TETON-1 met its primary efficacy endpoint, with nebulized Tyvaso demonstrating statistically significant improvement in absolute FVC relative to placebo from baseline to week 52 in an IPF population broadly treated with background therapy. The median change in FVC at week 52 was −43.3 mL (95% confidence interval [CI], −92.1 to −9.1) in the nebulized Tyvaso group and −196.2 mL (95% CI, −227.1 to −155.6) in the placebo group; between-group difference was 130.1 mL (95% CI, 82.2 to 178.1; P<0.001).....Combined analyses of TETON-1 and TETON-2 showed that nebulized Tyvaso achieved statistically significant treatment effects compared to placebo from baseline to week 52 for the primary endpoint and for most key secondary endpoints."

P3 data • Idiopathic Pulmonary Fibrosis

Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. (PubMed, N Engl J Med) - P3 | "In patients with IPF, treatment with inhaled treprostinil led to a smaller decline in FVC and fewer clinical-worsening events than placebo over the course of 52 weeks. (Funded by United Therapeutics; TETON-1 ClinicalTrials.gov number, NCT04708782.)."

Journal • P3 data • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF) (clinicaltrials.gov) - P3 | N=698 | Recruiting | Sponsor: United Therapeutics | N=242 ➔ 698

Enrollment change • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

United Therapeutics Corporation Reports First Quarter 2026 Financial Results (United Therapeutics Press Release) - "Total Tyvaso revenues decreased by two percent to $457.5 million in the first quarter of 2026, compared to $466.3 million in the first quarter of 2025, driven by a decrease in Nebulized Tyvaso revenues, partially offset by growth in Tyvaso DPI revenues. The growth in Tyvaso DPI revenues resulted primarily from an increase in quantities sold of $16.0 million and, to a lesser extent, a price increase. The decrease in Nebulized Tyvaso revenues resulted primarily from a decrease in U.S. quantities sold of $33.3 million and, to a lesser extent, a decrease in international revenues, partially offset by a price increase."

Sales • Pulmonary Arterial Hypertension

Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF) (clinicaltrials.gov) - P3 | N=698 | Recruiting | Sponsor: United Therapeutics | N=236 ➔ 698

Enrollment change • Immunology • Pulmonary Disease • Respiratory Diseases

United Therapeutics Corporation Announces TETON-1 Pivotal Study of Tyvaso Meets Primary Endpoint for Treatment of Idiopathic Pulmonary Fibrosis, Exceeding Impressive Treatment Effect Seen in TETON-2 (Businesswire) - "Integrated analyses of TETON-1 and TETON-2 showed statistically significant treatment effects compared to placebo from baseline to week 52 for the primary endpoint of change in absolute FVC by 111.8 mL (H-L estimate, 95% CI, 79.7 to 144.0; p <0.0001) and most secondary endpoints, including time to first clinical worsening and first acute exacerbation of IPF and changes in percent predicted FVC, K-BILD score, and DLCO....Additional TETON-1 study results and data from the integrated analyses of TETON-1 and TETON-2 will be presented at the American Thoracic Society Annual Meeting in Orlando in May 2026."

P3 data • Idiopathic Pulmonary Fibrosis

United Therapeutics plans to seek priority review of a supplemental New Drug Application, to be submitted to the U.S. Food and Drug Administration (FDA) by the end of this summer, to add IPF to the labeled indications for nebulized Tyvaso based on data from the TETON-1 and TETON-2 studies. (Businesswire)

FDA filing • Idiopathic Pulmonary Fibrosis

Breathing Easy: Cases of Transitioning Between Inhaled Prostacyclin Products (SCCM 2026) - "Once optimized, patients are often transitioned back to maintenance medications, however there is minimal to no evidence to guide the transition from nebulized epoprostenol to inhaled treprostinil products.Description: We present 3 patients with PH who were successfully transitioned from nebulized epoprostenol to inhaled treprostinil DPI (Tyvaso DPI®) or nebulizer (Tyvaso®) using multiple approaches. Pulmonologists specialized in PH and pharmacists are uniquely suited to develop treatment plans for transitioning patients between these high-risk medications. Further research and discussion regarding transitions between these inhaled agents would be beneficial to inform patient specific strategies in the future."

Clinical • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

United Therapeutics plans to submit a supplemental New Drug Application (sNDA) to the FDA by the second half of 2026 to add IPF to the labeled indications for nebulized Tyvaso following results from the ongoing TETON-1 study, which are expected soon (United Therapeutics Press Release)

FDA filing • P3 data • Idiopathic Pulmonary Fibrosis

United Therapeutics Corporation Announces Full Results of TETON-2 Phase 3 Clinical Trial Published in The New England Journal of Medicine (United Therapeutics Press Release) - "The study met its primary efficacy endpoint, with nebulized Tyvaso demonstrating statistically significant improvement in absolute FVC relative to placebo from baseline to week 52 in an IPF population broadly treated with background therapy. The median change in FVC at week 52 was −49.9 mL (95% confidence interval [CI], −79.2 to −19.5) in the nebulized Tyvaso group and −136.4 mL (95% CI, −172.5 to −104.0) in the placebo group, and the between group difference was 95.6 mL (95% CI, 52.2 to 139.0; P<0.001). Nebulized Tyvaso reduced risk of a clinical worsening event by 29% (hazard ratio, 0.71; 95% CI, 0.53 to 0.95; P=0.02) relative to placebo, a statistically significant improvement in this key secondary endpoint."

P3 data • Idiopathic Pulmonary Fibrosis

Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. (PubMed, N Engl J Med) - P3 | "In patients with IPF, inhaled treprostinil was associated with a smaller decline in FVC and fewer clinical-worsening events than placebo over a period of 52 weeks. (Funded by United Therapeutics; TETON-2 ClinicalTrials.gov number, NCT05255991.)."

Journal • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

The Minimal Important Difference in N-Terminal Pro-Brain Natriuretic Peptide in Pulmonary Hypertension. (PubMed, Chest) - "The estimated MID for short-term NT-proBNP improvement in PAH and PH-ILD is remarkably similar at 48%. Achievement of the MID for NT-proBNP change is strongly associated with clinically important outcomes in both PAH and PH-ILD, demonstrating that measuring NT-proBNP change over 12-16 weeks can be informative for prognosis and may be useful for decisions regarding treatment escalation in individuals with PAH and PH-ILD."

Journal • Cardiovascular • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • NPPB

TETON-PPF Clinical Trial of Inhaled Treprostinil for the Treatment of Progressive Pulmonary Fibrosis (ATS 2026) - No abstract available

Clinical • Immunology • Pulmonary Disease • Respiratory Diseases

TETON-1 Phase 3 Clinical Trial of Inhaled Treprostinil for the Treatment of Idiopathic Pulmonary Fibrosis (ATS 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

TETON Phase 3 Clinical Trials of Inhaled Treprostinil for the Treatment of Idiopathic Pulmonary Fibrosis: Integrated Efficacy and Safety Results for TETON-1 and TETON-2 (ATS 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

TETON: Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=598 | Completed | Sponsor: United Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

SAPPHIRE: Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension (clinicaltrials.gov) - P2 | N=5 | Completed | Sponsor: University of Florida | Recruiting ➔ Completed | N=10 ➔ 5 | Trial completion date: Jul 2026 ➔ Dec 2025

Enrollment change • Trial completion • Trial completion date • Cardiovascular • Hypertension • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sarcoidosis