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

Clinical Snapshot

Key Findings

• P Value: P < 0.001 for primary outcome

• Effect Size: Least squares mean difference -2.04% trunk fat reduction

• Primary Outcome: Trunk percent fat reduction: -1.68% vs +0.37% (placebo)

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: Not reported in abstract

Clinical Application

Once-weekly dosing may improve adherence compared to daily injections, though cost and PBS listing considerations apply Would require TGA approval and PBS evaluation. Current PBS covers daily somatropin for adult GHD under specific criteria. Weekly dosing could reduce injection burden but cost-effectiveness needs assessment Adults with confirmed growth hormone deficiency requiring hormone replacement therapy

Abstract

CONTEXT: 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. OBJECTIVE: This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. METHODS: The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. RESULTS: At week 38, lonapegsomatropin significantly reduced trunk percent fat (-1.68% vs +0.37%; least squares [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. CONCLUSION: The foresiGHt trial met its primary efficacy end point 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.

References

1. 1.Biller, B. M. K., Gilis-Januszewska, A., Doknic, M., Pico, A. M., Fleseriu, M., Raverot, G., Isidori, A. M., Takahashi, Y., Garcia, J. M., Silverstein, J. M., Bancos, I., Fukuoka, H., Huang, E., Kang, J., Komirenko, A. S., Domrzalski, L., Shu, A. D., Beckert, M., & Yuen, K. C. J. (2026). Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results. The Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgaf680