YUTREPIA was investigated in the Phase 3 INSPIRE trial and follow-up extension study in patients with PAH1,2
STUDIED IN PROSTACYCLIN-NAÏVE AND TYVASO® TRANSITION GROUPS2
INSPIRE was a 2-month, Phase 3, open-label, multicenter trial that studied YUTREPIA in 121 patients with PAH who were NYHA FC II or III at baseline1,2
ERA=endothelin receptor antagonist; NT-proBNP=N-terminal pro B-type natriuretic peptide; NYHA FC=New York Heart Association functional class; PDE-5i=phosphodiesterase 5 inhibitor; sGC=soluble guanylate cyclase agonist.
View dosing chart
Dose comparison between TYVASO® nebulizer and YUTREPIA1,3
See initial results
YUTREPIA builds upon the established safety and efficacy of inhaled treprostinil solution1,2
- The safety and efficacy of inhaled treprostinil solution were initially established in a 12-week, randomized, double-blind, placebo-controlled, multicenter study of patients with pulmonary arterial hypertension (PAH) who were also receiving bosentan or sildenafil1
- The trial met the primary efficacy endpoint—at week 12, patients who received inhaled treprostinil solution had a placebo-corrected median change from baseline in peak 6MWD of 20 meters (P < 0.001)1
6MWD = 6-minute walk distance; ERA = endothelin receptor antagonist; MLHFQ = Minnesota Living with Heart Failure Questionnaire; NYHA FC = New York Heart Association functional class; PDE-5i = phosphodiesterase 5 inhibitor; QID = four times daily; sGC = soluble guanylate cyclase agonist
YUTREPIA MADE IT POSSIBLE TO TITRATE TO HIGHER THERAPEUTIC DOSES1,2
Mean dose of YUTREPIA over 2 years in patients with PAH who were naive to prostacyclin therapy or transitioning from TYVASO® in the INSPIRE trial(1,2,4)
At 1 year1,3,4
- 41.5% (n = 39/94) of patients reached a dose of ≥132.5 mcg QID (equivalent to 15 to 17 breaths of TYVASO®)
- 3 patients reached 212 mcg QID (equivalent to ≥24 breaths of TYVASO®)
At 2 years1,3,4
- 32.5% (n = 26/80) of patients reached a dose of ≥159 mcg QID (equivalent to ≥18 breaths of TYVASO®)
- 1 patient reached 238.5 mcg QID (equivalent to ≥27 breaths of TYVASO®)
All YUTREPIA doses are QID
PATIENTS TRANSITIONING FROM TYVASO® SHOWED A 19-METER IMPROVEMENT AT MONTH 22,4,
6MWD was an exploratory endpoint in patients with PAH.
PROGRESSIVE IMPROVEMENT IN 6MWD WITH ESCALATING DOSES IN PATIENTS NAÏVE TO PROSTACYCLIN THERAPY2,4,*,†,‡
In a post hoc analysis, patients received increasing doses and showed improvement in 6MWD with YUTREPIA through 2 years1,2,4,*,†
Overall, mean 6MWD at baseline was 401 meters.2
Data from the efficacy population, which included all patients who received at least 1 dose and completed at least 1 efficacy assessment.2
This post hoc analysis excluded 1 patient whose baseline 6MWD was 560 meters and 2-month 6MWD was 181 meters as the day after the later test was performed, the patient was hospitalized with influenza and voluntarily withdrew from the study.4
6MWD was an exploratory endpoint.
INDICATION AND IMPORTANT SAFETY INFORMATION
- Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).
- Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%).
WARNINGS AND PRECAUTIONS
- Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with treprostinil may produce symptomatic hypotension.
- Treprostinil inhibits platelet aggregation and increases the risk of bleeding.
- Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness.
- Like other inhaled prostaglandins, YUTREPIA may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with YUTREPIA.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
- The concomitant use of treprostinil with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.
- Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8.
- Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.
- Safety and effectiveness in pediatric patients have not been established.
- Placebo-controlled clinical studies of treprostinil inhalation solution did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. The open label INSPIRE study in patients with PAH included 28 patients aged 65 and over in which no age-related differences were noted. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.
- Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency.
- No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis.
ADVERSE REACTIONS
- PAH (WHO Group 1): The safety and tolerability of YUTREPIA was evaluated in an open label study (INSPIRE) of 121 patients with PAH (WHO Group 1 and NYHA Functional Class II [80 patients] and Class III [41 patients]) followed for up to 2 months. The most commonly reported adverse reactions included cough, headache, throat irritation, dizziness, which are known side effects of treprostinil inhalation solution. The adverse reactions in the INSPIRE study were consistent with those observed in previous studies of inhaled treprostinil.
- PH-ILD (WHO Group 3): In a 16-week, placebo-controlled study of 326 patients with PH-ILD (WHO Group 3), adverse reactions with inhaled treprostinil were similar to the experience in studies of PAH.
Please see Full Prescribing Information for YUTREPIA.
To report SUSPECTED ADVERSE REACTIONS or PRODUCT COMPLAINTS click here.
You may also report side effects to Liquidia at 1-888-393-LQDA (5732) or FDA at http://www.fda.gov/MedWatch or call 1-800-FDA-1088.
The risk information provided here is not comprehensive. To learn more about YUTREPIA, talk with your healthcare provider. Please see Full Prescribing Information for YUTREPIA and Instructions for Use. For additional information, call 1-888-393-5732.
- Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).
- Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%).
WARNINGS AND PRECAUTIONS
- Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with treprostinil may produce symptomatic hypotension.
- Treprostinil inhibits platelet aggregation and increases the risk of bleeding.
- Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness.
- Like other inhaled prostaglandins, YUTREPIA may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with YUTREPIA.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
- The concomitant use of treprostinil with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.
- Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8.
- Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.
- Safety and effectiveness in pediatric patients have not been established.
- Placebo-controlled clinical studies of treprostinil inhalation solution did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. The open label INSPIRE study in patients with PAH included 28 patients aged 65 and over in which no age-related differences were noted. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.
- Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency.
- No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis.
ADVERSE REACTIONS
- PAH (WHO Group 1): The safety and tolerability of YUTREPIA was evaluated in an open label study (INSPIRE) of 121 patients with PAH (WHO Group 1 and NYHA Functional Class II [80 patients] and Class III [41 patients]) followed for up to 2 months. The most commonly reported adverse reactions included cough, headache, throat irritation, dizziness, which are known side effects of treprostinil inhalation solution. The adverse reactions in the INSPIRE study were consistent with those observed in previous studies of inhaled treprostinil.
- PH-ILD (WHO Group 3): In a 16-week, placebo-controlled study of 326 patients with PH-ILD (WHO Group 3), adverse reactions with inhaled treprostinil were similar to the experience in studies of PAH.
Please see Full Prescribing Information for YUTREPIA.
To report SUSPECTED ADVERSE REACTIONS or PRODUCT COMPLAINTS click here.
You may also report side effects to Liquidia at 1-888-393-LQDA (5732) or FDA at http://www.fda.gov/MedWatch or call 1-800-FDA-1088.
The risk information provided here is not comprehensive. To learn more about YUTREPIA, talk with your healthcare provider. Please see Full Prescribing Information for YUTREPIA and Instructions for Use. For additional information, call 1-888-393-5732.
References
- YUTREPIA. Prescribing information. Liquidia Technologies, Inc; 2025.
- Hill NS, Feldman JP, Sahay S, et al; INSPIRE study investigators. INSPIRE: safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH). Pulm Circ. 2022;12(3):e12119. doi:10.1002/pul2.12119
- Simon MA, Shapiro SM, Sahay S, et al. Clinical outcomes of YUTREPIA® dose in 6MWD and quality of life. Poster presented at: CHEST 2022 Annual Meeting; October 16-19, 2022; Nashville, TN.
- Data on file. Liquidia Technologies, Inc.