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Vital Status SubstudyOrenitram was associated with a positive impact on survival1*

Orenitram was associated with a 37% reduction in risk of death vs placebo at study closure (P=0.03)1†

Due to data collection limitations, data must be interpreted cautiously

Time to Death at Study Closure1
FREEDOM-EV PAH survival rate data vs placebo
  • P-value was calculated with log-rank test stratified by background PAH therapy and baseline 6MWD category.
  • Hazard ratio, 95% CI, and P-value were calculated with proportional hazard model with treatment, background PAH therapy, and baseline 6MWD as explanatory variables.

View vital status substudy

In FREEDOM-EV, vital status was collected throughout the study from patients who agreed to be followed. This included patients who discontinued early and those who transitioned to the OLE study1

  • When vital status was collected, cause of death was not specified1
  • Due to the collection of vital status occurring after some participants had exited the study and some investigative sites had closed, vital status was collected for 89% of patients (43 Orenitram, 31 placebo patients unknown)1
  • At the time of study closure, 11% of patients in the Orenitram group died vs 17.4% of patients in the placebo group (P=0.03)1
Difference in risk of death was not statistically significant at the end of randomized treatment period or OLE1§
  • FREEDOM-EV study closed after the occurrence of approximately 205 adjudicated events.1
  • FREEDOM-EV OLE study is ongoing. Data as of October 2018.

Summary of Deaths (All Causes)1

Time PointOrenitram
n=346
n (%)		Placebo
n=344
n (%)		Cox Hazard Ratio
(95% CI)
P-Value (Orenitram-Placebo)		Log-Rank
P-Value*
Deaths at end
of randomized
treatment		17 (4.9%)18 (5.2%)1 (0.52-1.95)
P=0.99		P=0.98
Deaths in OLE13 (3.8%)24 (7%)  
Deaths in
randomized
study and OLE†		30 (8.7%)42 (12.2%)0.80 (0.50-1.28)
P=0.36		P=0.43
Deaths in early
discontinuation
participants		8 (2.3%)18 (5.2%)  
Total deaths at
study closure		38 (11%)60 (17.4%)0.63 (0.42-0.95)
P=0.03		P=0.03

Due to data collection limitations, data must be interpreted cautiously

Vital status confirmed for 89% of initial participants; unknown for 43 Orenitram and 31 placebo1
  • P-values were stratified by background therapy and baseline 6MWD.
  • In the Orenitram group, 213 of 346 patients transitioned to the OLE. In the placebo group, 258 of 344 patients transitioned to the OLE.1
View Adverse Events in FREEDOM-EV

Important Safety Information

Contraindications

  • 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.

Adverse Reactions

  • 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.

Drug Interactions

  • Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.

Specific Populations

  • 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.

Indication

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%).

OREISIhcpOCT19

Please see Full Prescribing Information and Patient Information for Orenitram.

For additional information, call 1-877-UNITHER (1-877-864-8437).

6MWD=6-minute walk distance; CI=confidence interval; HR=hazard ratio; OLE=open-label extension; PAH=pulmonary arterial hypertension.

Reference: 1. Data on file. United Therapeutics Corporation. Research Triangle Park, NC.