Growth hormone deficiency in adults remains a commonly underappreciated and underrecognized diagnosis in endocrinology. Despite quietly eroding body composition, metabolic health, and quality of life, it has long been managed with a daily injection regimen that many patients do not sustain.
With lonapegsomatropin (Skytrofa), developed as TransCon hGH, earning US Food and Drug Administration approval for adult GH deficiency in July 2025, clinicians now have a once-weekly alternative. New long-term extension data presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 by Julie Silvertein, MD, a Professor of Medicine and Neurological Surgery and Medical Director of the Pituitary Center at Washington University, offer a more comprehensive picture of how it performs over time.
Lonapegsomatropin’s approval for this indication built upon previous August 2021 approval for the treatment of pediatric growth hormone deficiency in children ≥ 1 year of age weighing ≥ 26 pounds. The latest approval was based on results from foresiGHt, a phase 3 randomized, parallel-arm, placebo-controlled, double-blind, and active-controlled clinical trial that compared the efficacy and safety of weekly lonapegsomatropin with weekly placebo and daily somatropin in adults with growth hormone deficiency.
foresiGHt Trial Design and Extension
The trial randomly assigned 259 adults with growth hormone deficiency aged 23 to 80 years old in a 1:1:1 ratio, titrated to receive a target fixed dose of lonapegsomatropin, placebo, or daily hGH. Randomization was based on age and oral estrogen intake, with approximately equivalent hGH mg/week for lonapegsomatropin and daily hGH.
Of the 248 participants who completed treatment in the foresiGHt trial, 220 (88.7%) continued into the extension trial for up to 90 weeks and 202 (91.8%) participants completed 52 weeks of treatment in the extension trial.
Key Findings
Across 236 lonapegsomatropin-treated participants from both trials, the most common AEs were nasopharyngitis (9.7%), upper respiratory tract infection (9.3%), headache (8.1%), COVID-19 (7.2%), arthralgia (6.4%), and injection site reactions (5.1%). Most were mild or moderate, and treatment discontinuations due to AEs occurred in 3.8% of participants.
Results showed mean hemoglobin A1c remained stable within the reference range throughout all 90 weeks. Additionally, immunogenicity was low, with anti-hGH and anti-lonapegsomatropin antibodies each detected in 3.4% of participants and anti-PEG binding antibodies in 0.9%. All were low titer, transiently detected, and no neutralizing antibodies were identified.
Of note, weekly average IGF-1 SDS was maintained within the normal reference range through week 90 across all groups. Participants previously on placebo showed appropriate IGF-1 increases after initiating lonapegsomatropin, converging toward the reference range during re-titration and remaining stable thereafter.
Additionally, body composition improved across all 3 prior-treatment groups from the foresiGHt baseline through week 90, with reductions in trunk percent fat, trunk fat mass, and visceral adipose tissue, alongside gains in total body lean mass and trunk lean mass.
Patient-reported outcomes also reflected durable benefit. Using TRIM-AGHD, responder rates at week 90, defined as a reduction of ≥ 10 points from baseline, were 43.5%, 40.6%, and 35.8% in the lonapegsomatropin/lonapegsomatropin, placebo/lonapegsomatropin, and somatropin/lonapegsomatropin groups, respectively, with mean score reductions of approximately 19-23 points across groups.
References
Silverstein JM, Gilis-Januszewska A, Doknic M, et al. Long-term Safety and Efficacy of Lonapegsomatropin in Adults With Growth Hormone Deficiency: Results From a 52-Week Open-Label Extension Trial. Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, April 22-24, 2026.
