Date: 2015-06-08
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Diabetes Association Scientific Sessions in Boston, Massachusetts
Company: AntriaBio (USA - CO)
Product: AB101
Action
mechanism: basal insulin/protein. AB101, is a once-a-week injectable basal insulin to be administered by subcutaneous injection and is intended for use in patients with Type 1 and Type 2 diabetes who require basal insulin for the control of hyperglycemia. The formulation has been designed to release human insulin slowly and uniformly over a period of approximately one week without an adverse initial burst of insulin. Unlike existing basal insulin replacement therapies which use synthetic insulin analogues, AB101 is formulated from human recombinant insulin. The extended duration of action is the result of the PEGylation (PEG) of human insulin which is then encapsulated into poly-lactic, poly-glycolic (PLGA) microspheres. Typically, PEGylated biomolecules use large molecular weight PEG chains to decrease clearance and therefore reduce injection frequency.This patented formulation uses a very small molecular weight PEG for AB101 to modify the solubility of insulin, permitting encapsulation of the drug into a biodegradable polymer which determines the extended release profile. After injection, the PEGylated insulin is slowly released at the injection site as the polymer microspheres are broken down by simple hydrolysis.
Disease: diabetes
Therapeutic area: Metabolic diseases
Country:
Trial details:
Latest
news: * On June 8, 2015, AntriaBio, a biopharmaceutical corporation developing novel extended release therapies, released preclinical results for its lead product candidate, AB101, at the American Diabetes Association 75th Scientific Sessions® in Boston. The results demonstrated that AB101 has comparable in vitro pharmacology to native insulin, and in two animal species exhibited a prolonged subcutaneous insulin absorption profile, resulting in slow onset, peakless and sustained insulin levels with corresponding glucose reductions, without acute hypoglycemia caused by an insulin burst. These observations occurred at clinically relevant dose projections, demonstrating proof of concept of the potential for AB101 as a weekly subcutaneous basal insulin therapy in patients with diabetes mellitus. In receptor binding studies, AB101 drug substance was found to have an affinity for the insulin receptor that is similar to native insulin once bound, which predicts insulin activity in humans. The drug substance also displayed a low affinity for the IGF-1 receptor, which would indicate a low risk of mitogenicity. In liver cells, AB101 drug substance inhibited glucose production to the same magnitude and with the same potency as native insulin. The inhibitory effect on glucose production occurred at an IC50 of 0.24 nM, which was nearly identical to that of native insulin at an IC50 of 0.23 nM. In vivo studies were conducted in rats and dogs. Fasting insulin and glucose were measured at baseline and multiple times over a 14-day period after a single subcutaneous dose (37.5 mg/kg or vehicle control in rats [n=6/group]; 10 mg/kg or 37.5 mg/kg in dogs [n=3/group]). In both species, slow and sustained increases in insulin were observed, with a Cmax of > 30 ng/mL at 7 - 9 days post dose, and corresponding dose and species-dependent maximum reductions in glucose of 30 - 50%. The ratio of AUC(0-24h) to AUC(0-total) for insulin and glucose was < 1%. A similar sustained PK/PD profile was demonstrated in a diabetes animal model. AntriaBio is currently engaged in additional studies for AB101 that support the filing of an Investigational New Drug (IND) application with the FDA.
