Endocrine Abstracts

GH is an important regulator of longitudinal growth in children and metabolism in adults. GH is used for treatment deficiency disorders in both children and adults. GH treatment is safe and well tolerated. However, its clinical use is limited to daily s.c. injections which poses a challenge for both the patients and the physicians and has prompted research into alternative approaches to GH treatment.

NNC0195-0092 is a hGH derivative conjugated with an albumin binding moiety. The in vivo pharmacodynamic and pharmacokinetic properties of NNC195-0092 have been studied in hypophysectomised rats, mini-pigs and cynomolgus monkeys.

NNC0195-0092 induced dose-dependent increase in body weight of hypophysectomised rats and increase in plasma IGF1 levels in rats, mini-pigs, and cynomolgus monkeys. Multiple once weekly dosing of hypophysectomised rats induced a step-wise increase in body weight with an initial linear growth the first 3–4 days in each dosing interval. During the 28 days study period with 4 weekly doses, body weight increased by 52% compared to a vehicle control group. The IGF1 levels increased after each dose and returned to the same trough level in each dosing interval. Significant increases in body lean mass, tibia bone mineral content, and tibia cortical thickness were observed together with a decrease in body fat mass compared to a vehicle control group.

Pharmacokinetics in all three species has indicated a 1. order absorption from the subcutaneous tissue after a s.c. injection and a non-linear elimination. Apparent terminal half-lives of 5–6 h in rats, 10–12 h in mini-pigs, and 17–20 h in monkeys have been observed. The bioavailability was estimated to 39% in rats, 36% in mini-pigs, and 69% in monkeys.

In conclusion, once weekly s.c. administration of NNC0195-0092 exhibit pharmacokinetic and pharmacodynamic properties suggesting that NNC195-0092 is a potential once weekly GH candidate.