BioChaperone Technology Enables the Development of Pramlintide-Prandial Insulin Combinations

Pramlintide (Symlin®) is currently used on top of mealtime insulin therapy by T1D or T2D patients to achieve a better control of post-prandial glucose excursion. Indeed, pramlintide affects the rate of postprandial glucose appearance by slowing down gastric emptying, reducing postprandial glucagon secretion and modulating satiety, which affects caloric intake. Nevertheless, the use of pramlintide is currently limited as it cannot be combined with prandial insulin due to formulation pH incompatibility and results in a high burden of the number of injections. BioChaperone (BC) technology stabilizes pramlintide in aqueous solution at neutral pH and enables a pramlintide - prandial insulin co-formulation. BC pramlintide-human insulin (BC Pram Ins) formulation is physically and chemically stable for at least 6 weeks at 30°C and 9 weeks at 25°C. Physical stability was evidenced by visual inspection and MFI analysis. Chemical stability (recovery measured by RP-HPLC and high molecular weight species measured by SE-HPLC) was similar to that of commercial Humulin® and Symlin®. Under simulated in-use pump conditions at 37°C, BC Pram Ins formulation shows excellent physical and chemical stability for at least 1 week, with insulin and pramlintide recoveries higher than 95% and a formulation essentially free of particles. The pharmacokinetics of pramlintide was evaluated following single subcutaneous administration (0.1875 U/kg insulin, 1.125 µg/kg pramlintide) of BC Pram Ins formulation and pramlintide co-injected with human insulin (separate injections) to fasted healthy pigs. BC Pram Ins shows a slower absorption of pramlintide (LSM ratio [95% CI] ΔAUC_Pram0-30min: 0.45 [0.20; 1.05]) while the late exposure to pramlintide is higher (ΔAUC_{Pram60-180min}: 2.65 [1.44; 4.90]) compared to the separate injections.

In conclusion, the in-vitro and preclinical PD properties of BC Pram Ins support its clinical development to afford a better mealtime treatment for T1D and T2D patients.