Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Authors: Beverly M K Biller, Aleksandra Gilis-Januszewska, Mirjana Doknic, Antonio Miguel Pico, Maria Fleseriu, Gerald Raverot, Andrea M Isidori, Yutaka Takahashi, Jose M Garcia, Julie M Silverstein, Irina Bancos, Hidenori Fukuoka, Eric Huang, Jennifer Kang, Allison S Komirenko, Laurie Domrzalski, Aimee D Shu, Michael Beckert, Kevin C J Yuen
Institutions: Harvard University, Massachusetts General Hospital, Jagiellonian University, University of Belgrade, Univerzitetski Klinički Centar Srbije, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Oregon Health & Science University, Hospices Civils de Lyon, Sapienza University of Rome, Nara Medical University, University of Washington, Washington University in St. Louis, Mayo Clinic, Kobe University Hospital, Creighton University, Barrow Neurological Institute, University of Arizona, University of Arizona College of Medicine- Phoenix
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Funder: Ascendis Pharma Denmark
OpenAlex ID: W4417535031