Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results.

Abstract

Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. To evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273). This trial was conducted at 116 centers in North America, Europe, and Asia-Pacific. This trial randomized and dosed 259 adults with GHD. Participants were randomized 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy endpoint was change from baseline in trunk percent fat at week 38. Secondary efficacy endpoints included change from baseline in trunk fat mass and total body lean mass. At week 38, lonapegsomatropin significantly reduced trunk percent fat (-1.68% vs +0.37%; LS mean difference -2.04%, P<.001), increased total body lean mass (+1.60 kg vs -0.11 kg; LS mean difference 1.70 kg, P<.0001), and reduced trunk fat mass (-0.48 kg vs +0.22 kg; LS mean difference -0.70 kg, P=.0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. The foresiGHt trial met its primary efficacy endpoint by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.