- PE0139 was well tolerated; pharmacokinetic / pharmacodynamic profile supports once-weekly dosing
- PE0139 demonstrated synergistic action with weekly GLP-1 receptor agonist PB1023
Malvern, PA, June 7, 2015 – PhaseBio Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company and leader in the field of biopolymer-based drugs focused on developing treatments for metabolic and specialty cardiopulmonary disorders, announced positive Phase 1 safety and tolerability data supporting once-weekly dosing of its super-long-acting basal insulin, PE0139, in patients with type 2 diabetes during an oral presentation at the American Diabetes Association 75th Scientific Sessions in Boston. In addition, preclinical study results were presented today that demonstrated strong synergistic action of PE0139 with PhaseBio’s weekly GLP-1 receptor agonist PB1023.
PE0139 is in development for once-weekly use in type 2 diabetes. The company’s compounds are based on a proprietary Elastin-Like Polypeptides (ELP) technology, which uses recombinant ELP biopolymers to control the half-life, bioavailability and physical characteristics of molecules in order to achieve prolonged exposure and once-weekly dosing.
“We are extremely excited about the pharmacokinetic profile achieved with PE0139 and the potential for once-weekly dosing of basal insulin,” said Jonathan P. Mow, Chief Executive Officer of PhaseBio. “The product is liquid stable, ready-to-use and able to be combined with a long-acting GLP-1 such as PB1023, which would make for a convenient product presentation for weekly dosing. We look forward to advancing PE0139 into a Phase 2a multiple ascending dose study later this year.”
PE0139, the First Recombinant Fully Human Monomeric Super-Long-Acting Basal Insulin to Display a Sustained Nearly Peakless Insulin Profile Following a Single Subcutaneous Dose in Subjects with T2DM Supporting Weekly Dosing
The safety, tolerability, pharmacokinetic (PK) and preliminary pharmacodynamic (PD) response was evaluated in a randomized, double-blind, placebo-controlled, single ascending dose study of PE0139 in which 37 (24 active and 13 placebo) adults with type 2 diabetes with hemoglobin A1c between 6.0 and 10.0 (inclusive) on a basal insulin plus at least one oral antihyperglycemic agent were enrolled. Subjects were taken off basal insulin one week prior to dosing and were randomized in sequential order to one of four doses (0.05 mg/kg – 1.35 mg/kg).
No dose-limiting toxicities, serious adverse events or hypoglycemia were reported. Related treatment-emergent adverse events occurring in > five percent of subjects were confined to mild injection site erythema (eight percent). PE0139 demonstrated dose-related increases in mean serum drug concentrations, mean decreases in fasting plasma glucose compared to placebo [range -2 to -34 mg/dL, p=0.06], and consistently lower free fatty acid levels compared to placebo [all PE0139 pooled group mean: -0.35 meq/L, p<0.05] measured seven days after dosing. PE0139 was well tolerated and displayed a PK / PD profile supporting once-weekly dosing.
“This is a very exciting first step in the development of a once-weekly insulin formulation, which could be a game changer in the management of diabetes,” said John Buse, MD, Ph.D., Chief of the Division of Endocrinology at the University of North Carolina School of Medicine.
Synergistic Action of PE0139, a Super-Long-Acting Basal Insulin, and PB1023 a Weekly GLP-1 Receptor Agonist
A proof-of-principal study in db/db mice was conducted with subcutaneously administered PE0139, PB1023 and a co-formulation to evaluate the effect on fasting plasma glucose (FPG) followed by an intraperitoneal glucose tolerance test. When sub-therapeutic doses of the individual components were administered in a co-formulation, FPG and glucose tolerance were normalized.
Additionally, administration of a co-formulation of PE0139 and a rapid-acting insulin-ELP to STZ-treated mice resulted in a rapid but sustained reduction in FPG. PK analysis indicated that sustained and rapid release ELP fusion proteins are independently released into the circulation.
PhaseBio Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing novel drugs to treat diabetes and cardiovascular dysfunction in patients suffering from rare diseases. The Company’s proprietary discovery platform technology uses recombinant ELP biopolymers to control the half-life, bioavailability and physical characteristics of molecules for ease of administration. The resulting compounds are tuned for a specific rate of absorption, thereby increasing efficacy and reducing side effects. The Company’s lead development candidates are PE0139, a novel super-long-acting basal insulin-ELP fusion for weekly dosing; and PB1046, a weekly VIP receptor agonist for treatment of acute and chronic heart failure and Duchenne muscular dystrophy-associated cardiomyopathy. PhaseBio is privately owned, with headquarters and research laboratories in Malvern, PA.