Mast Therapeutics, a clinical-stage biopharmaceutical company leveraging its molecular adhesion and sealant technology (MAST) platform to develop novel therapies for sickle cell disease, arterial disease and heart failure, plans to develop vepoloxamer (MST-188) for the treatment of patients with chronic heart failure. Encouraged by recently reported nonclinical results and input from experts in the field, the company expects to begin dosing in a phase II study of vepoloxamer in patients with chronic heart failure in the third quarter of this year.
Wilson S. Colucci M.D., professor of medicine and physiology and chief of cardiovascular medicine at Boston University School of Medicine, said, "The results from studies in experimental heart failure are encouraging and support clinical testing in patients with chronic heart failure. If shown to translate to patients with clinical heart failure, vepoloxamer may offer a way of directly improving LV contractile function by restoring cardiomyocyte membrane integrity and increasing their survival. Such a novel mechanism offers great potential for our patients."
Brian M. Culley, CEO of the company, said, "While we still are in the planning process, we expect the phase II study will be a randomized, double-blind, two-arm, placebo-controlled study of the safety and efficacy of a single administration of vepoloxamer in patients with chronic heart failure, including its effect on markers of cardiac injury (troponin) and wall stress (NT-proBNP), as well as clinical outcomes. We anticipate that the study will be conducted on an outpatient basis and enroll approximately 150 patients at sites in and outside of the U.S. Of note, we recently filed new patent applications claiming the use of vepoloxamer in this and other clinical settings of heart failure and will continue to identify ways to create additional value and protect the sizeable market opportunity of our vepoloxamer pipeline."
The company previously reported results from two randomized, placebo-controlled nonclinical studies of vepoloxamer in a model of chronic, stable heart failure produced by intracoronary microembolizations. In the first study, as reported last year, a single, two-hour administration of vepoloxamer resulted in robust improvements in key parameters of heart function, including left ventricular (LV) end-systolic volume, ejection fraction, stroke volume and cardiac output, which persisted for one to two weeks. In the second study, vepoloxamer was administered at the start of the study and a repeat treatment was administered three weeks after the first. The study concluded after a total of six weeks.
As the company reported earlier in March, the second study not only reproduced the treatment effect of the first study, but also showed that retreatment with vepoloxamer at three weeks after the initial administration improved upon the effects observed after the first administration. The effects observed after the second administration persisted for at least three weeks, until the end of the six-week study. Notably, after the second administration, LV ejection fraction had not returned to baseline values by the end of the study, but was still improved by approximately 20% above baseline. Vepoloxamer had no statistically significant effect on heart rate or blood pressure compared to control.