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Secondary EndpointsIn FREEDOM-EV, Orenitram demonstrated durable improvements across multiple prognostic risk factors1,2
Patients demonstrated statistically significant improvements in 6MWD at weeks 36 and 481*
- Change in 6MWD was not statistically significant at week 241
- Baseline median 6MWD was 405 m.1
- Least squares mean, P-values, and estimated difference were from the MMRM with the change in 6MWD from baseline as dependent variable, treatment, week, treatment-by-week interaction as the fixed effects, and baseline 6MWD as covariate. MMRM is a statistical analysis that does not require imputation of missing data and considers the entirety of the data.
- Placebo-adjusted change.
Orenitram reduced NT-proBNP, an important indicator of right ventricle dysfunction1,3
- Statistically significant reductions in NT-proBNP were seen as early as week 12 (P=0.0002)1
- P-value was obtained from the analysis of covariance with change from baseline in log-transformed data in NT-proBNP as the dependent variable, treatment as fixed effect, and log-transformed baseline NT-proBNP as a covariate.
Orenitram is the only oral prostacyclin-class therapy that has demonstrated improvements in WHO FC1,4
Statistically significant improvements in functional class were seen as early as week 12 with Orenitram (P=0.0009) and were maintained through week 48 (P=0.0028)1*
- Functional class was not measured at week 60. P-values were obtained from Fisher’s exact test.1
Important Safety Information
- Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure.
Warnings and Precautions
- Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.
- The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.
- In the 12-week, placebo-controlled, monotherapy study, and an event-driven, placebo-controlled, combination therapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw, pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain.
- Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.
- Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies with Orenitram in pregnant women.
- It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.
- Safety and effectiveness of Orenitram in pediatric patients have not been established.
- Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. Caution should be used when selecting a dose for geriatric patients.
- There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients.
Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%).
6MWD=6-minute walk distance; FC=functional class; MMRM=mixed model repeated measure; NT-proBNP=N-terminal pro–B-type natriuretic peptide; WHO=World Health Organization.
References: 1. Data on file. United Therapeutics Corporation. Research Triangle Park, NC. 2. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Respir J. 2015;46(4):903-975. 3. Warwick G, Thomas PS, Yates DH. Biomarkers in pulmonary hypertension. Eur Respir J. 2008;32(2):503-512. 4. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2019.