United Therapeutics Announces BREEZE Study of Investigationa
Jan 28, 2021 6:11:29 GMT -5
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Post by kite on Jan 28, 2021 6:11:29 GMT -5
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Study demonstrated safety and tolerability of Tyvaso DPI™ in patients with PAH transitioning from Tyvaso® Inhalation Solution
A separate study in healthy volunteers demonstrated comparable treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution
Tyvaso DPI NDA filing anticipated in April 2021 with priority review
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., Jan. 28, 2021 /PRNewswire/ -- United Therapeutics Corporation (Nasdaq: UTHR) announced today that that the BREEZE study of Tyvaso DPI (inhaled treprostinil) met its primary objective of demonstrating safety and tolerability in patients with pulmonary arterial hypertension (PAH) transitioning from Tyvaso (treprostinil) Inhalation Solution. In addition, a pharmacokinetic (PK) study in healthy volunteers demonstrated comparable treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution.
Tyvaso DPI is a next-generation dry powder formulation of Tyvaso currently under development. If approved, Tyvaso DPI is expected to provide a more convenient method of administration as compared with traditional nebulized Tyvaso therapy.
"We are pleased with these results, which demonstrate the safety, tolerability, and pharmacokinetic profiles of treprostinil administered as Tyvaso DPI," said Dr. Leigh Peterson, Vice President, Product Development at United Therapeutics. "We look forward to submitting our New Drug Application for Tyvaso DPI in April. If approved, we expect Tyvaso DPI will provide a major advancement in the delivery of inhaled treprostinil therapy, offering convenience benefits compared to our existing Tyvaso nebulizer."
United Therapeutics intends to submit a New Drug Application (NDA) to the FDA for Tyvaso DPI for indications covering PAH and pulmonary hypertension associated with interstitial lung disease in April 2021 and plans to apply a priority review voucher to the Tyvaso DPI NDA, providing an expedited FDA review period.
The BREEZE study demonstrated safety and tolerability of Tyvaso DPI in subjects with PAH transitioning from Tyvaso Inhalation Solution
The BREEZE study was a single-sequence study in which 51 subjects on a stable regimen of Tyvaso Inhalation Solution were transitioned to Tyvaso DPI at a corresponding treprostinil dose. The primary objective of the study was to evaluate the safety and tolerability of Tyvaso DPI during a three-week treatment phase in PAH patients previously treated with Tyvaso Inhalation Solution.
Secondary objectives of the study were to evaluate: (1) the systemic exposure and pharmacokinetics of treprostinil when delivered as Tyvaso Inhalation Solution and Tyvaso DPI; (2) six-minute walk distance (6MWD) at study entry and after three weeks of treatment with Tyvaso DPI; (3) the long-term safety and tolerability of Tyvaso DPI during an optional extension phase (OEP) in patients previously treated with Tyvaso Inhalation Solution; (4) patient satisfaction with and preference for inhaled treprostinil devices assessed at study entry when patients were using Tyvaso Inhalation Solution and after three weeks using Tyvaso DPI; and (5) patient-reported PAH symptoms and impact (PAH-SYMPACT®) assessed at study entry when patients were using Tyvaso Inhalation Solution and after three weeks using Tyvaso DPI.
Primary safety and tolerability objective. Transition from Tyvaso Inhalation Solution to Tyvaso DPI was safe and well tolerated. Forty-nine out of 51 patients (96%) completed the treatment phase and there were no study drug related adverse events. Most adverse events experienced during the study were mild to moderate in severity and occurred at severities and frequencies consistent with those seen in other inhaled treprostinil studies in patients with PAH.
Secondary objectives. Three weeks after switching from Tyvaso Inhalation Solution to Tyvaso DPI, patients in the BREEZE study demonstrated:
Improvements in 6MWD compared to baseline. These improvements in 6MWD compared to baseline were sustained in the OEP through the data cut-off date.
Improvements in overall satisfaction with the Tyvaso DPI inhaler compared to the Tyvaso Inhalation Solution nebulizer at baseline using an internally developed satisfaction and preference questionnaire.
Improvement in patient-reported outcomes using the validated PAH-SYMPACT questionnaire.
Optional extension phase. Subjects in BREEZE were given the opportunity to continue in an OEP. All subjects who completed the treatment phase (49/51) elected to continue in the OEP.
PK data collected during the BREEZE study are currently undergoing final analysis. Detailed data from the BREEZE study will be presented in upcoming publications and scientific conferences.
Tyvaso DPI demonstrated comparable treprostinil exposure to Tyvaso Inhalation Solution in healthy volunteers
The healthy volunteer PK study was a randomized six-period, six-sequence crossover study of three dose levels of Tyvaso DPI and three dose levels of Tyvaso Inhalation Solution in 36 healthy volunteers. The primary objective of the study was to evaluate the systemic exposure and PK of treprostinil administered as Tyvaso DPI and Tyvaso Inhalation Solution. Secondary objectives of the study evaluated the safety and tolerability of Tyvaso DPI.
Study results. Subjects demonstrated comparable systemic treprostinil exposure for each corresponding Tyvaso DPI and Tyvaso Inhalation Solution dose level. Between-subject variability for both AUC0-5h and Cmax was approximately 50% less for Tyvaso DPI compared to Tyvaso Inhalation Solution, suggesting a more precise dosing profile for Tyvaso DPI relative to nebulized Tyvaso.
Safety. The adverse event profile for Tyvaso DPI in healthy volunteers was consistent with known prostacyclin effects and previous studies of Tyvaso Inhalation Solution.
Detailed data from the healthy volunteer PK study will be presented in upcoming publications and scientific conferences.
Study demonstrated safety and tolerability of Tyvaso DPI™ in patients with PAH transitioning from Tyvaso® Inhalation Solution
A separate study in healthy volunteers demonstrated comparable treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution
Tyvaso DPI NDA filing anticipated in April 2021 with priority review
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., Jan. 28, 2021 /PRNewswire/ -- United Therapeutics Corporation (Nasdaq: UTHR) announced today that that the BREEZE study of Tyvaso DPI (inhaled treprostinil) met its primary objective of demonstrating safety and tolerability in patients with pulmonary arterial hypertension (PAH) transitioning from Tyvaso (treprostinil) Inhalation Solution. In addition, a pharmacokinetic (PK) study in healthy volunteers demonstrated comparable treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution.
Tyvaso DPI is a next-generation dry powder formulation of Tyvaso currently under development. If approved, Tyvaso DPI is expected to provide a more convenient method of administration as compared with traditional nebulized Tyvaso therapy.
"We are pleased with these results, which demonstrate the safety, tolerability, and pharmacokinetic profiles of treprostinil administered as Tyvaso DPI," said Dr. Leigh Peterson, Vice President, Product Development at United Therapeutics. "We look forward to submitting our New Drug Application for Tyvaso DPI in April. If approved, we expect Tyvaso DPI will provide a major advancement in the delivery of inhaled treprostinil therapy, offering convenience benefits compared to our existing Tyvaso nebulizer."
United Therapeutics intends to submit a New Drug Application (NDA) to the FDA for Tyvaso DPI for indications covering PAH and pulmonary hypertension associated with interstitial lung disease in April 2021 and plans to apply a priority review voucher to the Tyvaso DPI NDA, providing an expedited FDA review period.
The BREEZE study demonstrated safety and tolerability of Tyvaso DPI in subjects with PAH transitioning from Tyvaso Inhalation Solution
The BREEZE study was a single-sequence study in which 51 subjects on a stable regimen of Tyvaso Inhalation Solution were transitioned to Tyvaso DPI at a corresponding treprostinil dose. The primary objective of the study was to evaluate the safety and tolerability of Tyvaso DPI during a three-week treatment phase in PAH patients previously treated with Tyvaso Inhalation Solution.
Secondary objectives of the study were to evaluate: (1) the systemic exposure and pharmacokinetics of treprostinil when delivered as Tyvaso Inhalation Solution and Tyvaso DPI; (2) six-minute walk distance (6MWD) at study entry and after three weeks of treatment with Tyvaso DPI; (3) the long-term safety and tolerability of Tyvaso DPI during an optional extension phase (OEP) in patients previously treated with Tyvaso Inhalation Solution; (4) patient satisfaction with and preference for inhaled treprostinil devices assessed at study entry when patients were using Tyvaso Inhalation Solution and after three weeks using Tyvaso DPI; and (5) patient-reported PAH symptoms and impact (PAH-SYMPACT®) assessed at study entry when patients were using Tyvaso Inhalation Solution and after three weeks using Tyvaso DPI.
Primary safety and tolerability objective. Transition from Tyvaso Inhalation Solution to Tyvaso DPI was safe and well tolerated. Forty-nine out of 51 patients (96%) completed the treatment phase and there were no study drug related adverse events. Most adverse events experienced during the study were mild to moderate in severity and occurred at severities and frequencies consistent with those seen in other inhaled treprostinil studies in patients with PAH.
Secondary objectives. Three weeks after switching from Tyvaso Inhalation Solution to Tyvaso DPI, patients in the BREEZE study demonstrated:
Improvements in 6MWD compared to baseline. These improvements in 6MWD compared to baseline were sustained in the OEP through the data cut-off date.
Improvements in overall satisfaction with the Tyvaso DPI inhaler compared to the Tyvaso Inhalation Solution nebulizer at baseline using an internally developed satisfaction and preference questionnaire.
Improvement in patient-reported outcomes using the validated PAH-SYMPACT questionnaire.
Optional extension phase. Subjects in BREEZE were given the opportunity to continue in an OEP. All subjects who completed the treatment phase (49/51) elected to continue in the OEP.
PK data collected during the BREEZE study are currently undergoing final analysis. Detailed data from the BREEZE study will be presented in upcoming publications and scientific conferences.
Tyvaso DPI demonstrated comparable treprostinil exposure to Tyvaso Inhalation Solution in healthy volunteers
The healthy volunteer PK study was a randomized six-period, six-sequence crossover study of three dose levels of Tyvaso DPI and three dose levels of Tyvaso Inhalation Solution in 36 healthy volunteers. The primary objective of the study was to evaluate the systemic exposure and PK of treprostinil administered as Tyvaso DPI and Tyvaso Inhalation Solution. Secondary objectives of the study evaluated the safety and tolerability of Tyvaso DPI.
Study results. Subjects demonstrated comparable systemic treprostinil exposure for each corresponding Tyvaso DPI and Tyvaso Inhalation Solution dose level. Between-subject variability for both AUC0-5h and Cmax was approximately 50% less for Tyvaso DPI compared to Tyvaso Inhalation Solution, suggesting a more precise dosing profile for Tyvaso DPI relative to nebulized Tyvaso.
Safety. The adverse event profile for Tyvaso DPI in healthy volunteers was consistent with known prostacyclin effects and previous studies of Tyvaso Inhalation Solution.
Detailed data from the healthy volunteer PK study will be presented in upcoming publications and scientific conferences.
