Once-weekly somatrogon improves body composition parameters and is well-tolerated in adults with growth hormone deficiency

Adult Growth Hormone Deficiency (aGHD) is characterized by altered body composition, reduced bone mineral density, and impaired quality of life. Traditional growth hormone (GH) replacement therapy typically requires daily subcutaneous injections, which can lead to poor patient adherence and treatment burden. The development of long-acting GH preparations, such as somatrogon, aims to reduce injection frequency, thereby improving compliance and potentially enhancing therapeutic outcomes for patients requiring lifelong treatment. This study addresses the need for convenient and effective long-term management strategies for aGHD.

This phase 3, randomized, double-blind, placebo-controlled study evaluated somatrogon in adults with GHD. A total of 202 patients were randomized 2:1 to receive once-weekly somatrogon or placebo for a 26-week double-blind period (Period 1), with dosing adjusted for gender, age, and estrogen therapy. All patients then received somatrogon in subsequent open-label extension periods. The primary endpoint was the change in trunk fat mass from baseline to Week 26. Secondary endpoints included changes in total fat mass, lean body mass (LBM), and percentage change in trunk fat mass. Safety was assessed via adverse events (AEs) and laboratory evaluations.

Of 202 randomized patients, 198 received treatment (133 somatrogon; 65 placebo). Mean IGF-I SDS normalized following somatrogon initiation. While there was no significant difference between somatrogon and placebo in the primary endpoint, change in trunk fat mass from baseline to Week 26 (-0.37 kg vs 0.03 kg; p=0.0821), somatrogon demonstrated significant improvements in several key body composition parameters.

Somatrogon significantly improved lean body mass (LBM), trunk fat mass as a percentage of total fat mass, and three supplemental endpoints including trunk LBM and appendicular skeletal muscle mass. The incidence of adverse events was similar between the somatrogon and placebo groups, with most events reported as mild to moderate in severity, indicating a favorable safety profile. These findings suggest that despite not meeting the primary endpoint for trunk fat mass, somatrogon effectively modulated other crucial aspects of body composition.