The need

There is a high unmet need for a stable, rapid-acting, ultra-concentrated insulin of up to 1000 U/mL, which will not only offer a vastly superior mealtime insulin product for people requiring >200 U/day, but is also a critical step towards the advancement of the miniaturisation of insulin delivery devices. Next-generation device technology such as wearable, continuous administration patch pumps and implants are critical future developments for people living with diabetes, improving glycaemic control and compliance, thus reducing adverse states such as hypoglycaemia and diabetic ketoacidosis, as well as overall complications and mortality. Currently available prandial insulins such as Novolog® and Humalog® are only available at concentrations of up to 100 and 200 U/mL respectively. The development of stable aqueous rapid acting formulations of insulins at concentrations of up to 1000 U/mL will significantly reduce the dosing volume. Thus far, the development of a highly concentrated stable formulation of insulin that is rapid acting has proven elusive. Increasing insulin concentration is a significant formulation challenge both from an in vitro and in vivo perspective. In vitro, it leads to an increase in viscosity and impairment of stability. In vivo, increasing the concentration of insulin delays the onset of action which is undesirable from a clinical outcomes perspective.

Product concept

A commercially viable ultra-concentrated prandial insulin product must demonstrate an onset of action that is comparable to the current prandial insulins formulated at 100 or 200 U/mL. In addition, the stability of the product, both with respect to the shelf-life and the in-use period must not be inferior to that of the current prandial products. Arecor has applied its proprietary platform technology to overcome the in vitro and in vivo challenges to optimize an ultra-concentrated insulin at up to 1000 U/mL with a pharmacokinetic and pharmacodynamic profile that is at least equivalent to the current marketed rapid acting low-concentration insulin analogues.

Status

Arecor has completed the formulation development, demonstrating formulations of insulin analogues at concentrations between 500 and 1000 U/mL with rapid onset in a validated diabetic pig model as well as an excellent stability profile. The formulation development was supported by the Juvenile Diabetes Research Foundation (JDRF). The product is currently in pre-clinical development stage and the first human clinical trial is planned for 2018.

Utilising its innovative technology Arecor has developed a series of proprietary stable aqueous rapid-acting, ultra-concentrated insulin (up to 1,000 U/mL) formulations, which will not only offer a vastly superior mealtime insulin product for people requiring >200 U/day, but is also a critical step towards the advancement of the miniaturisation of delivery devices.