- First patients dosed in Part One, which is evaluating PB1046 in subjects with heart failure
- Part Two will examine PB1046 in subjects with cardiac dysfunction secondary to Duchenne muscular dystrophy; initiation expected fourth quarter 2016
Malvern, PA, August 8, 2016 — PhaseBio Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on biopolymer-based drugs for orphan, cardiopulmonary and metabolic diseases, today announced the dosing of the first patients in Part One of a Phase 2a clinical study of PB1046, a once-weekly vasoactive intestinal peptide (VIP) receptor agonist in development for the treatment of cardiopulmonary disorders. Part One will assess PB1046 in adult subjects with stable heart failure with reduced ejection fraction. Part Two, which PhaseBio expects to initiate later in 2016, will examine PB1046 in subjects with cardiac dysfunction secondary to Duchenne muscular dystrophy.
“There is a clear need for heart failure treatments that both alleviate symptoms and slow or reverse disease progression,” said John Lee, M.D., Ph.D., Chief Medical Officer of PhaseBio. “We look forward to building on our compelling preclinical data in models of heart failure, and the positive data from our Phase 1 studies, which demonstrated the safety and tolerability of PB1046 at efficacious doses in patients with hypertension.”
Part One is a randomized, double-blind, placebo-controlled, multiple-dose study evaluating the safety, tolerability, and pharmacokinetic and pharmacodynamic response following four weeks of once-weekly subcutaneous injections of PB1046 in 28 adults with heart failure. Dose levels shown to be safe and well-tolerated in Part One will be selected for evaluation in Part Two of the study.
“This is an important milestone in the progression of our pipeline and the expansion of our programs in cardiopulmonary disorders and orphan diseases,” said Jonathan P. Mow, Chief Executive Officer of PhaseBio. “We look forward to initiating Part Two of this study later this year in DMD patients with cardiomyopathy, which is a leading cause of death in people suffering from this devastating disease.”
For additional information on the study, please visit: https://clinicaltrials.gov/ct2/show/NCT02808585.
PB1046 is based on vasoactive intestinal peptide (VIP), a naturally occurring neuropeptide that exerts its physiological effects through activation of the G-protein coupled receptors VPAC1 and VPAC2, which are widely distributed throughout the cardiovascular, pulmonary and immune systems. To date, the inherently poor in vivo stability and bioavailability of the native peptide have limited its therapeutic use. PB1046 is a genetic fusion of an analogue of VIP with PhaseBio’s elastin-like polypeptide biopolymer, which overcomes these limitations and demonstrates prolonged circulatory drug exposure and potent activity. PB1046 was designed to be relatively selective in binding to the VPAC2 receptor to reduce potential gastrointestinal side effects believed to be associated with excessive activation of the VPAC1 receptor.
PB1046 has been shown to be highly effective in animal models of hypertension, pulmonary arterial hypertension and heart failure, with positive cardiac inotropic (contractility) and lusitropic (relaxation) effects without an increase in myocardial oxygen demand. Additional pre-clinical data demonstrated that chronic administration of PB1046 in a murine model of DMD (mdx mouse) significantly slowed the deterioration of cardiac function.
In a Phase 1 single-ascending-dose study, PB1046 was well-tolerated and demonstrated a prolonged, dose-dependent effect on blood pressure when administered subcutaneously to patients with essential hypertension. This supported a second Phase 1 single-ascending-dose study in patients with essential hypertension, in which PB1046 was administered intravenously to support use in an acute setting.
PB1046 has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of cardiomyopathy associated with dystrophinopathies.
PhaseBio Pharmaceuticals is a clinical-stage biopharmaceutical company focused on biopolymer-based drugs for orphan, cardiopulmonary and metabolic diseases. The Company’s proprietary technology platform uses recombinant elastin-like polypeptide (ELP) biopolymers to control the half-life, bioavailability and physical characteristics of molecules for ease of administration. The resulting compounds are engineered for a specific rate of absorption to enhance efficacy and reduce side effects. PhaseBio’s lead development candidates include: PE0139, a novel, super-long-acting basal insulin-ELP fusion for once-weekly dosing; and PB1046, a weekly vasoactive intestinal peptide receptor agonist for the treatment of cardiomyopathy associated with Duchenne muscular dystrophy, Becker muscular dystrophy and X-linked dilated cardiomyopathy, and other indications. PhaseBio is privately owned, with headquarters and research laboratories in Malvern, PA. For more information, please visit www.phasebio.com.
Laura Bagby, 6 Degrees