Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Tyvaso is a prostacyclin mimetic indicated for the treatment of: 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%). FDA label
Also known as Treprostinil Inhalation Powder, Treprostinil, Inhaled Treprostinil, Tyvaso Inhalation Solution, Tyvaso, oral treprostinil, Inhaled Treprostinil (Tyvaso Nebulizer)
Tyvaso (treprostinil) · 14 trials · 13 indications
The FVC measurement indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath.
Incidence of AEs and SAEs, incidence of abnormal clinical laboratory parameters, abnormal vital signs, and abnormal 12-lead ECGs
Assess the effect of continued therapy with oral treprostinil on exercise capacity as assessed by the change from Baseline in 6-Minute Walk Test (6MWT) after 1 year of treatment. The 6MWT is the clinical standard for assessing subject functional status in the treatment of PAH and has been considered an objective measure of subject functional status by the American Thoracic Society. The distance a subject can walk in 6 minutes is recorded in meters.
Change in peak 6-minute walk distance from baseline to Week 12. Peak 6MWD was defined as a 6-minute walk test (6MWT) within 10 to 60 minutes after study drug inhalation
American Thoracic Society (ATS) Practice Guideline based 6-minute walk (6MW) distance
Change in RHC parameter PVR (pulmonary vascular resistance )
Change in RHC parameter mPAP (mean pulmonary arterial pressure)
Number of participants with treatment-related adverse events following treatment with oral treprostinil at 12 months. We defined adverse event as any untoward medical experience occurring to a subject during a clinical trial whether or not it is related to the study drug.
Median rate of change of calcinosis in radiograph following treatment with oral treprostinil as assessed by the Scleroderma Clinical Trial Consortium (SCTC) radiographic scoring system. Historical average SCTC scores in this patient population have ranged from 4.08 to 472.88, with higher scores indicating more severe symptoms. The SCTC radiographic score for calcinosis is a validated radiographic scoring system to assess the severity of calcinosis affecting the hands of patients with SSc that accounts for area coverage, density, and anatomic location, higher scores mean worse calcinosis. Physician rates density and percentage of area for 22 regions of each hand, each deferentially weighted in the overall score; individual region values are multiplied my their weight then summed to create an overall score.
Defined as the region with ventilation signals \< mean - 2SD, measured by HP129XeMRI and expressed as a percentage of total lung volume.
Defined as the region with membrane signals \< mean - 2SD, measured by HP129XeMRI and expressed as a percentage of total lung volume.
Defined as the region with membrane signals between 1SD and 2SD below the mean, measured by HP129XeMRI and expressed as a percentage of total lung volume.
Defined as the region with RBC transfer signals \< mean - 2SD, measured by HP129XeMRI and expressed as a percentage of total lung volume.
Defined as the region with RBC transfer signals between 1SD and 2SD below the mean, measured by HP129XeMRI and expressed as a percentage of total lung volume.
Measured using HP129XeMRI spectroscopy as a surrogate for pulmonary vascular resistance, normalized to RBC transfer signal intensity.
Frequency shift in RBC signal reflecting capillary blood oxygenation, measured using HP129XeMRI spectroscopy.
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Peak exposure 6MWD will occur by conducting 6-minute walk test (6MWT) within 10 to 60 minutes after the most recent dose of study drug dose.
A successful transition was defined as a subject from Cohort 1 or Cohort 2 who was receiving oral treprostinil and no longer receiving IV/SC Remodulin or inhaled prostacyclin, respectively, at Week 4 and clinically maintained on oral treprostinil treatment through Week 24. A successful initiation of oral treprostinil for Cohort 3 was defined as a subject who was clinically maintained on oral treprostinil through Week 24.
6MWD was evaluated at study entry and after 3 weeks of treatment with TreT.
Subject satisfaction with and preference for the inhaled treprostinil device was evaluated with the Preference Questionnaire for Inhaled Treprostinil Devices (PQ-ITD). The PQ-ITD is a questionnaire given to evaluate subject satisfaction with and preference for inhaled treprostinil devices. The questionnaire provides 12 different statements around inhaled device satisfaction and allows for 5 response options: strongly disagree, disagree, neutral, agree, and strongly agree.
Patient-reported PAH symptoms and impact were evaluated with the PAH Symptoms and Impact (PAH-SYMPACT) Questionnaire. The PAH-SYMPACT is a 23-item patient-reported outcome questionnaire that consists of 11 symptom items, 11 impact items, and 1 item on oxygen use. The symptom items are divided into cardiopulmonary and cardiovascular domains, and the impact items are divided into physical and emotional/cognitive domains. Symptom and impact domain scores (range 0 to 4) are calculated as the sum of the scores for the items included in the domain divided by the number of items in the domain. For all domains, a higher score indicates more severe symptoms/impacts.
Patient-reported PAH symptoms and impact were evaluated with the PAH Symptoms and Impact (PAH-SYMPACT) Questionnaire. The PAH-SYMPACT is a 23-item patient-reported outcome questionnaire that consists of 11 symptom items, 11 impact items, and 1 item on oxygen use. The symptom items are divided into cardiopulmonary and cardiovascular domains, and the impact items are divided into physical and emotional/cognitive domains. Symptom and impact domain scores (range 0 to 4) are calculated as the sum of the scores for the items included in the domain divided by the number of items in the domain. For all domains, a higher score indicates more severe symptoms/impacts.
Stroke volume augmentation is a physiologic parameter which reflects the hearts ability to respond to physiologic demands of exercise. Stroke volume can be inferred during cardiopulmonary exercise testing by calculating the O2 pulse. Oxygen uptake (VO2) and heart rate are directly measured during cardiopulmonary exercise testing. O2 pulse is calculated by dividing VO2 by heart rate. Stroke volume augmentation is the ratio of O2 pulse at baseline (at the beginning of exercise) and at anaerobic threshold. Stroke volume augmentation will be measured before and after treatment with inhaled treprostinil to assess for improvements in heart function during exercise.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Matching placebo inhaled using an ultrasonic nebulizer QID |
| Inhaled Treprostinil | EXPERIMENTAL | Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose. |
| Oral Treprostinil | EXPERIMENTAL | Subjects from previous studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405), TDE-PH-301 (NCT00325442), TDE-PH-302 (NCT00325403), or TDE PH-308 (NCT00887978). Subjects were instructed to take the appropriate amount of 0.125, 0.25, 0.5, 1, and/or 2.5 mg tablets based upon their prescribed dose. Investigators were instructed to increase the dose of oral treprostinil in the absence of dose limiting drug-related AEs to ensure each subject received the optimal clinical dose throughout the study |
| Treprostinil-treated | EXPERIMENTAL | Patients with pulmonary fibrosis with an advanced pulmonary hypertension phenotype will be treated with parenteral treprostinil in an open-label fashion |
| Study Group | EXPERIMENTAL | Sarcoidosis patients with interstitial lung disease and precapillary pulmonary hypertension based on right heart catheterization (RHC). All subjects will initiate inhaled treprostinil at a dose of 3 breaths (18 mcg) four times daily. Study drug doses escalations (additional one breath four times daily) can occur every three days with a maximum dosing regimen of up to 12 breaths (72 mcg) four times daily, as clinically tolerated. |
| Inhaled Treprostinil in COPD Patients With Hypoxemia and Preserved DLCO | EXPERIMENTAL | - |
| Cohort 1 (Transitioning from Parental) | EXPERIMENTAL | Transitioned from IV or SC Remodulin to oral treprostinil |
| Cohort 2 (Transitioning from Inhaled) | EXPERIMENTAL | Transitioned from inhaled prostacyclin to oral treprostinil |
| Cohort 3 (Add-on to Current PAH Therapy) | EXPERIMENTAL | Treated with oral treprostinil as a de novo add-on to current PAH therapy |
| Tyvaso to TreT | EXPERIMENTAL | Each subject received a corresponding dose of TreT for 3 weeks during the Treatment Phase based on the subject's current stable Tyvaso dose. |
| Treatment group | EXPERIMENTAL | Single arm, every participant will receive inhaled treprostinil |
| Name | Type | Description |
|---|---|---|
| Placebo | DRUG | Placebo administered QID |
| Inhaled Treprostinil | DRUG | Inhaled treprostinil (6 mcg/breath) administered QID |
| Treprostinil Ultrasonic Nebulizer | DEVICE | Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. |
| Oral Treprostinil | DRUG | Oral sustained release tablet, twice or thrice daily. Open label study with active drug, no other intervention arms. |
| Placebo inhalation solution | DRUG | Doses are titrated to 9 breaths four times daily. |
| Treprostinil | DRUG | For both SQ and IV routes, treprostinil will be started in the hospital at 1ng/kg/min and titrated up by 1ng/kg/min every 1-3 days as tolerated |
| Inhaled Treprostinil (Tyvaso Nebulizer) | DRUG | Participants will receive inhaled Treprostinil (Tyvaso nebulizer), 6 µg per breath, administered four times daily for 4 weeks. The starting dose will be 3 breaths per session. The dose will increase by 1 breath per session each week, as tolerated, to a target of 6 breaths per session by week 4. If adverse effects occur, participants will remain at the highest tolerated dose. The drug will be administered using the Tyvaso inhalation system provided by United Therapeutics. No changes to baseline COPD maintenance medications are allowed during the treatment period. Participants will be monitored for safety throughout the study. |
| Treprostinil Inhalation Powder | DRUG | Treprostinil inhalation powder single-use cartridges containing either 32 or 48 micrograms of treprostinil per cartridge (QID) |
Inclusion Criteria: 1. Subject gives voluntary informed consent to participate in the study. 2. Subject is ≥18 years of age, inclusive, at the time of signing informed consent. 3. Subject has radiological evidence of pulmonary fibrosis of \>10% extent on an HRCT scan in the previous 12 months (conf...
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Tyvaso is an inhaled treprostinil therapy developed for pulmonary hypertension conditions, including pulmonary arterial hypertension and pulmonary hypertension. It is also being studied in chronic obstructive pulmonary disease with hypoxemia, idiopathic pulmonary fibrosis, and progressive pulmonary fibrosis. United Therapeutics Corporation is the developer.
Tyvaso targets PTGIR, the prostacyclin receptor, and acts as an agonist. Treprostinil binds this receptor to produce its pharmacological effect. PTGIR agonism is the mechanism underlying the drug's activity across the pulmonary and fibrotic conditions being studied.
Tyvaso is developed by United Therapeutics Corporation, which trades under the ticker UTHR. The company is responsible for the treprostinil programs across inhaled and oral formulations, including the studies in pulmonary hypertension, COPD, and pulmonary fibrosis.
Tyvaso is in clinical development, with studies spanning early phase 1 through phase 3. The phase 3 TETON-PPF trial in progressive pulmonary fibrosis is recruiting, and a phase 2 trial in COPD with hypoxemia is also recruiting. It is investigational for these indications.
Tyvaso trials include NCT05943535, a phase 3 study in progressive pulmonary fibrosis, and NCT05255991, a completed phase 3 study in idiopathic pulmonary fibrosis. NCT07037836 is a recruiting phase 2 trial in COPD with hypoxemia, and NCT07116681 is an early phase 1 study in exercise induced pulmonary hypertension.
Yes, Tyvaso is a brand name for treprostinil. The same active molecule is also referred to as inhaled treprostinil, treprostinil inhalation powder, Tyvaso inhalation solution, Tyvaso nebulizer, and oral treprostinil, depending on the formulation and delivery method.