Positive Interim Results Of Aironite Phase 2 Study Presented At 4th Annual Drug Discovery And Development Symposium For Pulmonary Hypertension
- Category: Small Molecules
- Published on Tuesday, 11 July 2017 14:38
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Aironite Significantly Lowered Pulmonary Artery Pressures and Significantly Increased Pulmonary Arterial Compliance
AUSTIN, TX, USA I July 11, 2017 I Savara, Inc. (NASDAQ: SVRA), a clinical-stage specialty pharmaceutical company focused on the development and commercialization of novel therapies for the treatment of serious or life-threatening rare respiratory diseases, today reported positive interim results from an ongoing 50-patient open-label Phase 2 study of Aironite in patients with pulmonary hypertension (PH) from multiple different etiologies. The results were presented in an invited lecture at the 4th Annual Drug Discovery and Development Symposium for Pulmonary Hypertension on July 10th, 2017 by lead investigator Marc A. Simon, M.D., M.S., F.A.C.C., Associate Professor of Medicine, Bioengineering, and Clinical Translational Science and Director, Heart Failure Research / Clinical Hemodynamics Core Facility, at the Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute at the University of Pittsburgh.
In the 41 patients enrolled to date in the study, administration of Aironite significantly improved multiple hemodynamic measures, with most pronounced improvements in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). In the 10 PH-HFpEF patients analyzed, Aironite administration resulted in significant overall decreases in right atrial pressure, systolic and diastolic right ventricular pressure, systolic and diastolic pulmonary artery pressure, and pulmonary capillary wedge pressure. Of note, pulmonary capillary wedge pressure decreased by 7.5 mmHg (95% CI –9.0 to –6.0; baseline median value 18mmHg; p < 0.05) and mean pulmonary artery pressure decreased by 7.9 mmHg (95% CI –9.4 to –6.3; baseline median value 34 mmHg; p < 0.05). Pulmonary artery compliance (Cpa) was improved by 35% (+0.97 ml/mmHg, 95% CI +0.25 to +1.68; p < 0.01). Aironite was generally well-tolerated and no significant safety concerns were identified, supporting the primary safety outcome of the study.
"These additional results build upon prior interim data published last year in the Journal of Clinical Investigation, and demonstrate that Aironite can significantly improve cardiopulmonary hemodynamics in HFpEF as well as Group 3 PH patients, both clinical conditions which are inadequately treated by currently approved medicinal treatments," stated Taneli Jouhikainen, M.D., Ph.D., Chief Operating Officer of Savara. "If the observed short-term improvements are translated into clinically meaningful functional improvements in our ongoing placebo-controlled studies in HFpEF patients, we believe the product will have exciting potential to be advanced towards Phase 3 studies and hopefully an eventual NDA filing."
About the Phase 2 Study
This is an institution-sponsored, single-center, open-label Phase 2 study, the main objective of which is to investigate the hemodynamic effects and mechanisms of action of Aironite delivered in a single escalating dose to PH patients who undergo right heart catheterization. The study will enroll patients with PH from different etiologies, comprising 20 patients with advanced PH associated with heart failure with preserved ejection fraction (HFpEF-PH), 20 patients with pulmonary arterial hypertension who may be on standard PH therapy, and 10 patients with PH associated with advanced lung disease. Subjects receive a first dose of 45 mg of Aironite via nebulizer, with one subsequent escalation of dosage to 90 mg approximately 60 minutes after the first dose. During the study, right heart and pulmonary artery hemodynamics are measured continuously, and cardiac output is measured at 15 minute intervals, as well as noninvasive systemic blood pressure and pulse oximetry. Changes in hemodynamics and calculated pulmonary and systemic vascular resistances, as well as pulmonary artery compliance are performed utilizing standard formulas.
Aironite is a sodium nitrite solution for inhalation via nebulization that has demonstrated encouraging results in Phase 2 clinical trials conducted to date in patients with heart failure with preserved ejection fraction (HFpEF). Nitrite is a direct vasodilator and can be recycled in vivo to form nitric oxide (NO) independent of the classical NO synthase (NOS) pathway. Nitrite and Nitrite-mediated NO formation have multiple beneficial effects, including dilation of blood vessels, reduction in hemodynamic perturbations during exercise in the failing heart, and improvements in skeletal muscle bioenergetics and mitochondrial respiration, resulting in improved efficiency of oxygen utilization during submaximal exercise.
Savara is also supporting two placebo-controlled institution-sponsored Phase 2 studies of Aironite in patients with HFpEF, referred to as the INDIE and the INABLE studies. The main objective of the INDIE study is to assess the efficacy of Aironite on maximum exercise capacity (peakVO2), activity levels, and quality of life after four weeks of dosing, whereas the main objective of the INABLE study is assess the efficacy of Aironite on the same outcome measures when used in conjunction with supervised cardiac rehabilitation exercise training. Both studies are currently ongoing, and being conducted at leading U.S. based medical institutions.
Savara Inc. is a clinical-stage specialty pharmaceutical company focused on the development and commercialization of novel therapies for the treatment of serious or life-threatening rare respiratory diseases. Savara's pipeline comprises Molgradex, a Phase 3 stage inhaled granulocyte-macrophage colony-stimulating factor (or GM-CSF) for pulmonary arterial proteinosis (or PAP), AeroVanc, an inhaled vancomycin for MRSA infection in Cystic Fibrosis in preparation for Phase 3, and Aironite, an inhaled sodium nitrite in Phase 2 development. Savara's strategy involves expanding its pipeline of potentially best-in-class products through indication expansion, strategic development partnerships and product acquisitions, with the goal of becoming a leading company in its field. Savara's management team has significant experience in orphan drug development and pulmonary medicine, in identifying unmet needs, creating and acquiring new product candidates, and effectively advancing them to approvals and commercialization. More information can be found at www.savarapharma.com. (Twitter: @SavaraPharma)