Study met its primary endpoint; AIR001 was generally well-tolerated, with no treatment-related serious adverse events
SAN DIEGO, CA, USA I February 1, 2016 I Mast Therapeutics, Inc. (NYSE MKT: MSTX), a biopharmaceutical company developing novel clinical-stage therapies for sickle cell disease and heart failure, today reported positive top-line results from a blinded Phase 2a study of AIR001 for the treatment of heart failure with preserved ejection fraction (HFpEF) conducted at Mayo Clinic by lead investigator Barry A. Borlaug, M.D., Associate Professor of Medicine and Director, Circulatory Failure Research, Division of Cardiovascular Diseases, Department of Internal Medicine. In the Phase 2a study, AIR001 showed statistically significant improvement for the pre-specified primary endpoint: change in pulmonary capillary wedge pressure (PCWP) at 20 Watts exercise after drug treatment relative to PCWP at 20 Watts exercise in the initial assessment prior to drug treatment, compared to placebo-treated patients. Study data show that nebulized AIR001 attenuates the hemodynamic derangements of cardiac failure that occur during exercise in HFpEF patients. AIR001 was generally well-tolerated. Detailed study results are expected to be submitted for presentation at a scientific conference later this year.
“Heart failure with preserved ejection fraction is a major public health problem that has no proven effective treatment, yet currently afflicts 2 to 3 million Americans,” stated Dr. Borlaug. “One factor that complicates treatment is that the hemodynamic perturbations causing morbidity such as high filling pressures and low cardiac output are typically present only intermittently—being absent at rest but observed during stress such as exercise. As such, an ideal therapy would become more effective during stress, without untoward effects on resting cardiovascular function. The results observed with AIR001 in this study support our hypothesis that acute administration of nebulized inhaled sodium nitrite unloads the heart during exercise without excessive reduction in resting pressures or arterial blood pressure.”
“These results are an important step in validating our second asset and establishing the potential clinical utility of AIR001 in HFpEF,” stated Brian M. Culley, Chief Executive Officer of Mast Therapeutics. “Mayo Clinic is a well-known leader in the characterization and treatment of heart failure and we thank Dr. Borlaug for working with us and leading this study,” continued Mr. Culley. “We look forward to advancing AIR001 in this area of high unmet medical need for which there is no FDA-approved therapy available. We also anticipate reporting interim data from a second investigator-sponsored Phase 2a study of AIR001 in HFpEF patients around the middle of this year.”
About the Phase 2a Study Design
The Phase 2a study was a randomized, double-blind, placebo-controlled clinical trial of AIR001 in 30 patients with HFpEF referred to the catheterization laboratory for invasive exercise stress testing. Standard right heart catheterization using high fidelity micromanometers was performed at rest and during supine exercise with simultaneous expired gas analysis. Hemodynamic, arterial and mixed venous blood gas, as well as expired gas data were acquired at rest, during each exercise stage and at peak exercise. Venous blood samples were obtained at rest and at 20 Watt exercise. Perceived symptoms of dyspnea and fatigue will be quantified using the Borg dyspnea and effort scores at each stage of exercise.
The primary endpoint of the study measured PCWP at 20 Watts exercise after administration of study drug relative to PCWP at 20 Watts exercise in the initial assessment prior to administration of study drug. Secondary endpoints measured changes in resting PCWP after administration of study drug, as well as rest and exercise-related changes in right atrial pressure, PCWP, pulmonary artery pressure, pulmonary vascular resistance, systemic BP, heart rate, cardiac output, VO2, Ve/VCO2 slope and Borg dyspnea/effort scores. Sodium nitrite levels were evaluated at rest and 20 Watt exercise stages before and after study drug administration. Regression analysis was performed to explore how changes in NO2 levels relate to observed hemodynamic effects.
About AIR001
AIR001 is a sodium nitrite solution for intermittent inhalation via nebulization. Nitrite is a physiological signaling molecule with roles in intravascular endocrine nitric oxide (NO) production, hypoxic vasodilation signaling, and cytoprotection after ischemia-reperfusion. Nitrite serves as the largest physiologic reservoir of NO and can be converted to NO independent of nitric oxide synthase (NOS) activity. In experimental models, nitrite use has demonstrated improved remodeling both in the pulmonary vasculature and right ventricle. Hemodynamic effects include venodilation with reductions in right atrial pressures, pulmonary and systemic vasodilation with reductions in pulmonary vascular resistance and left atrial pressures, and improved cardiac relaxation. Mast Therapeutics obtained the AIR001 program through its acquisition of privately-held Aires Pharmaceuticals, Inc. in 2014.
About Mast Therapeutics
Mast Therapeutics, Inc. is a publicly traded biopharmaceutical company headquartered in San Diego, California. The Company is leveraging its MAST platform, derived from over two decades of clinical, nonclinical and manufacturing experience with purified and non-purified poloxamers, to develop vepoloxamer (also known as MST-188), its lead product candidate, for serious or life-threatening diseases and conditions typically characterized by impaired microvascular blood flow and damaged cell membranes. The Company is also developing AIR001, a sodium nitrite solution for inhalation via nebulization.
Vepoloxamer is an investigational new drug being tested in a pivotal Phase 3 study called EPIC for the treatment of vaso-occlusive crisis in patients with sickle cell disease and in a Phase 2 study for the treatment of patients with chronic heart failure. AIR001 is an investigational new drug in Phase 2a clinical development for treatment of patients with heart failure with preserved ejection fraction (HFpEF). More information can be found on the Company’s web site at www.masttherapeutics.com. (Twitter: @MastThera)
SOURCE: Mast Therapeutics
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Study met its primary endpoint; AIR001 was generally well-tolerated, with no treatment-related serious adverse events
SAN DIEGO, CA, USA I February 1, 2016 I Mast Therapeutics, Inc. (NYSE MKT: MSTX), a biopharmaceutical company developing novel clinical-stage therapies for sickle cell disease and heart failure, today reported positive top-line results from a blinded Phase 2a study of AIR001 for the treatment of heart failure with preserved ejection fraction (HFpEF) conducted at Mayo Clinic by lead investigator Barry A. Borlaug, M.D., Associate Professor of Medicine and Director, Circulatory Failure Research, Division of Cardiovascular Diseases, Department of Internal Medicine. In the Phase 2a study, AIR001 showed statistically significant improvement for the pre-specified primary endpoint: change in pulmonary capillary wedge pressure (PCWP) at 20 Watts exercise after drug treatment relative to PCWP at 20 Watts exercise in the initial assessment prior to drug treatment, compared to placebo-treated patients. Study data show that nebulized AIR001 attenuates the hemodynamic derangements of cardiac failure that occur during exercise in HFpEF patients. AIR001 was generally well-tolerated. Detailed study results are expected to be submitted for presentation at a scientific conference later this year.
“Heart failure with preserved ejection fraction is a major public health problem that has no proven effective treatment, yet currently afflicts 2 to 3 million Americans,” stated Dr. Borlaug. “One factor that complicates treatment is that the hemodynamic perturbations causing morbidity such as high filling pressures and low cardiac output are typically present only intermittently—being absent at rest but observed during stress such as exercise. As such, an ideal therapy would become more effective during stress, without untoward effects on resting cardiovascular function. The results observed with AIR001 in this study support our hypothesis that acute administration of nebulized inhaled sodium nitrite unloads the heart during exercise without excessive reduction in resting pressures or arterial blood pressure.”
“These results are an important step in validating our second asset and establishing the potential clinical utility of AIR001 in HFpEF,” stated Brian M. Culley, Chief Executive Officer of Mast Therapeutics. “Mayo Clinic is a well-known leader in the characterization and treatment of heart failure and we thank Dr. Borlaug for working with us and leading this study,” continued Mr. Culley. “We look forward to advancing AIR001 in this area of high unmet medical need for which there is no FDA-approved therapy available. We also anticipate reporting interim data from a second investigator-sponsored Phase 2a study of AIR001 in HFpEF patients around the middle of this year.”
About the Phase 2a Study Design
The Phase 2a study was a randomized, double-blind, placebo-controlled clinical trial of AIR001 in 30 patients with HFpEF referred to the catheterization laboratory for invasive exercise stress testing. Standard right heart catheterization using high fidelity micromanometers was performed at rest and during supine exercise with simultaneous expired gas analysis. Hemodynamic, arterial and mixed venous blood gas, as well as expired gas data were acquired at rest, during each exercise stage and at peak exercise. Venous blood samples were obtained at rest and at 20 Watt exercise. Perceived symptoms of dyspnea and fatigue will be quantified using the Borg dyspnea and effort scores at each stage of exercise.
The primary endpoint of the study measured PCWP at 20 Watts exercise after administration of study drug relative to PCWP at 20 Watts exercise in the initial assessment prior to administration of study drug. Secondary endpoints measured changes in resting PCWP after administration of study drug, as well as rest and exercise-related changes in right atrial pressure, PCWP, pulmonary artery pressure, pulmonary vascular resistance, systemic BP, heart rate, cardiac output, VO2, Ve/VCO2 slope and Borg dyspnea/effort scores. Sodium nitrite levels were evaluated at rest and 20 Watt exercise stages before and after study drug administration. Regression analysis was performed to explore how changes in NO2 levels relate to observed hemodynamic effects.
About AIR001
AIR001 is a sodium nitrite solution for intermittent inhalation via nebulization. Nitrite is a physiological signaling molecule with roles in intravascular endocrine nitric oxide (NO) production, hypoxic vasodilation signaling, and cytoprotection after ischemia-reperfusion. Nitrite serves as the largest physiologic reservoir of NO and can be converted to NO independent of nitric oxide synthase (NOS) activity. In experimental models, nitrite use has demonstrated improved remodeling both in the pulmonary vasculature and right ventricle. Hemodynamic effects include venodilation with reductions in right atrial pressures, pulmonary and systemic vasodilation with reductions in pulmonary vascular resistance and left atrial pressures, and improved cardiac relaxation. Mast Therapeutics obtained the AIR001 program through its acquisition of privately-held Aires Pharmaceuticals, Inc. in 2014.
About Mast Therapeutics
Mast Therapeutics, Inc. is a publicly traded biopharmaceutical company headquartered in San Diego, California. The Company is leveraging its MAST platform, derived from over two decades of clinical, nonclinical and manufacturing experience with purified and non-purified poloxamers, to develop vepoloxamer (also known as MST-188), its lead product candidate, for serious or life-threatening diseases and conditions typically characterized by impaired microvascular blood flow and damaged cell membranes. The Company is also developing AIR001, a sodium nitrite solution for inhalation via nebulization.
Vepoloxamer is an investigational new drug being tested in a pivotal Phase 3 study called EPIC for the treatment of vaso-occlusive crisis in patients with sickle cell disease and in a Phase 2 study for the treatment of patients with chronic heart failure. AIR001 is an investigational new drug in Phase 2a clinical development for treatment of patients with heart failure with preserved ejection fraction (HFpEF). More information can be found on the Company’s web site at www.masttherapeutics.com. (Twitter: @MastThera)
SOURCE: Mast Therapeutics
Post Views: 50
