BOSTON — Two new therapies — the super long-acting basal insulin PE0139 and the weekly glucagon-like peptide-1 (GLP-1) receptor agonist PB1023 — may lead to a novel approach for treating diabetes, according to data presented at the American Diabetes Association (ADA) 75th Scientific Sessions.
Both PE0139 and PB1023 are based on ELP biopolymer technology in which an inert repeating polymeric elastin-like peptide (ELP), which is expressed in Escherichia coli (E. coli), is fused to the protein of interest, such as insulin and GLP-1, respectively.
“Both products … are fully stable in a simple liquid formulation. On injection subcutaneously, they go through a heat-induced phase transition which leads to an effective depot being formed under the skin, and the product is then slowly released into the circulation and then slowly cleared from the circulation, so we get prolonged exposure through two distinct mechanisms,” Jim Ballance, PhD, an employee of PhaseBio Pharmaceuticals, which is developing PE0139 and PB1023, told Endocrinology Advisor.
PE0139 First-in-Man Clinical Trial
At this year's meeting, Poul Strange, MD, PhD, also an employee of PhaseBio Pharmaceuticals, presented data from a first-in-man dose escalation trial evaluating PE0139 in patients with type 2 diabetes.
HbA1c ranged from 6.0% to 10.0% and patients were taking a stable dose of basal insulin and at least one oral antihyperglycemic agent for 3 months before study entry. Insulin was withheld for 7 days before and 7 days after dose.
Results indicated that PE0139 demonstrated dose-related increases in mean serum concentrations and mean decreases in fasting plasma glucose (FPG) with PE0139 vs. placebo (–2 mg/dL to –34 mg/dL; P=.06). PE0139 also resulted in consistently lower free fatty acid levels vs. placebo, measured 7 days after dosing.
The researchers found no dose-limiting toxicities, as well as no severe adverse events or hypoglycemia. In more than 5% of patients, treatment-related adverse events included mild injection site erythema (8%).
“Results from the trial demonstrated that the pharmacokinetic properties of our new insulin will make it well suited for an injection once a week for patients, provided further development,” Strange told Endocrinology Advisor.
“The drug candidate was safe and well tolerated, and we were able to demonstrate the effect that we like to see with an insulin for these patients.”
Read more: http://www.endocrinologyadvisor.com/ada-75th-scientific-sessions-2015/insulin-glp-1-receptor-agonist-type-2-diabetes/article/421020/