ECEESPE2025 Oral Communications Oral Communications 14: Growth Axis and Syndromes (6 abstracts)
Results of the foresiGHt trial support the efficacy and safety of once-weekly lonapegsomatropin in adults with growth hormone deficiency (GHD)
Aleksandra Gilis-Januszewska 1 , Beverly M.K. Biller 2 , Mirjana Doknic 3 , Antonio Pico 4 , Maria Fleseriu 5 , Gerald Raverot 6 , Andrea Isidori 7 , Yutaka Takahashi 8 , Jose Garcia 9 , Julie M. Silverstein 10 , Irina Bancos 11 , Eric Huang 12 , Jennifer Kang 12 , Allison Komirenko 12 , Laurie Domrzalski 12 , Aimee Shu 12 , Michael Beckert 12 & Kevin CJ Yuen 13
1Jagiellonian University Medical College, Kraków, Poland; 2Massachusetts General Hospital, Boston, United States; 3Clinical Center of Serbia, Belgrade, Serbia; 4UNIVERSITY MIGUEL HERNANDEZ, Alicante, Spain; 5Oregon Health & Science University, Portland, United States; 6Hospices Civils de Lyon, Lyon, France; 7Sapienza University of Rome, Rome, Italy; 8Nara Medical University, Department of Diabetes and Endocrinology, Kashihara, Japan; 9University of Washington/Puget Sound VA/SIBCR, Issaquah, United States; 10Washington University, Clayton, United States; 11Mayo Clinic College of Medicine (Rochester) Endocrine Fellowship Program, Rochester, United States; 12Ascendis Pharma, Ind., Palo Alto, United States; 13University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, United States
JOINT3277
Background: Adult growth hormone deficiency (aGHD) is characterized by metabolic abnormalities due to insufficient growth hormone (GH) production. Lonapegsomatropin was designed to provide release of unmodified somatropin, and once-weekly injection reduces the burden of daily GH replacement therapy.
Methods: ForesiGHt was a randomized, parallel-3-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial to establish the efficacy and safety of lonapegsomatropin in aGHD. 259 adults with GHD across 21 countries who were GH treatment-naïve or not treated with GH in the prior year, randomized 1:1:1 to receive lonapegsomatropin, once-weekly placebo, or daily somatropin. Fixed dosing was based on age and oral estrogen intake, designed to be comparable across lonapegsomatropin and somatropin arms. Following a 12-week (w) titration to target maintenance dose, fixed doses were administered for 26w.
Results: Baseline characteristics were similar between arms. Lonapegsomatropin demonstrated superiority on the primary efficacy endpoint of change from baseline (CFB) in trunk percent fat at 38w vs placebo (lonapegsomatropin -1.7%, placebo 0.4%, LS mean difference -2.0%, P<0.0001) and key secondary efficacy endpoints of CFB in total body lean mass (lonapegsomatropin 1.6 kg, placebo -0.1 kg, LS mean difference 1.7 kg, P<0.0001) and CFB in trunk fat mass (lonapegsomatropin -0.5 kg, placebo 0.2 kg, LS mean difference -0.7 kg, P=0.0053). Mean total exposure and maintenance doses were similar for lonapegsomatropin and somatropin arms, with larger CFB in average IGF-I SDS mean at 38w in the lonapegsomatropin arm (1.4) vs somatropin arm (0.5). To assess outcomes at comparable weekly IGF-I exposure, a post-hoc analysis was done in participant subsets with average IGF-I SDS ≤1.75 SDS at 38w. Mean IGF-I SDS for these subsets were similar (lonapegsomatropin -0.1, somatropin -0.5), with comparable effects in fat and lean tissue compartments (CFB in trunk percent fat mean -2.4% and -2.6% respectively; CFB in total body lean mass mean 1.7 kg and 1.4 kg respectively). In the safety population, the incidence of severe AEs was low (lonapegsomatropin, 3.4%; placebo, 1.2%; somatropin, 2.3%) and the incidence of treatment-related AEs was similar (lonapegsomatropin 24.7%, somatropin 22.1%). Injection site reaction incidence was low and similar for lonapegsomatropin (4.5%), somatropin (5.8%) and placebo (4.8%), and A1c levels remained stable in all treatment arms.
Conclusions: The results of the foresiGHt trial indicate that lonapegsomatropin is an efficacious and tolerable replacement for endogenous GH. Once-weekly dosing may be impactful for adults with GHD who typically manage multiple other medical therapies.
Volume 110
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Endocrine Abstracts
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