FDA Approves Lonapegsomatropin-tcgd (Skytrofa), Formerly TransCon hGH, for Adult Growth Hormone Deficiency

The US Food and Drug Administration has approved Ascendis Pharma’s lonapegsomatropin-tcgd (Skytrofa), developed as TransCon hGH, for the replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).1

Announced on July 28, 2025, the 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 TransCon hGH with weekly placebo and daily somatropin in adults with GHD.1

“The abnormal body composition, dyslipidemia, and insulin resistance that are the hallmarks of adult GHD predispose affected individuals to serious medical complications such as metabolic syndrome, increased cardiovascular risk, and impaired quality of life – including cognitive dysfunction, depression, anxiety, sleep disturbance, and reduced physical and mental drive. Despite this, adherence to daily somatropin injections that have been the standard of care for more than 25 years remains a problem,” Kevin Yuen, MD, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine in Phoenix, said in a statement.1 “It is no surprise that patients are looking for a less burdensome treatment regimen, and a new treatment option such as [lonapegsomatropin], with once-weekly injection and its unique release of unmodified somatropin, is expected to help improve both real-world adherence and overall outcomes.”

First approved by the FDA in August 2021 for the treatment of pediatric GHD in children ≥ 1 year of age weighing ≥ 26 pounds, lonapegsomatropin is a prodrug of somatropin administered once weekly, providing sustained release of active, unmodified somatropin.1

Following its pediatric approval, an unmet need remained for adult GHD, a well-recognized medical condition where an individual’s body does not produce enough growth hormones, causing abnormalities in substrate metabolism, bone remodeling, body composition, and psychological symptoms, including cognitive impairment, social isolation, lack of motivation, and depression.2

Lonapegsomatropin’s use in adult patients with GHD was assessed in the foresiGHt trial, which compared the efficacy and safety of weekly lonapegsomatropin with weekly placebo and daily hGH. The trial randomly assigned 259 adults with GHD 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 TransCon hGH and daily hGH.2

Upon analysis, TransCon hGH achieved superiority on primary and key secondary efficacy endpoints at week 38, demonstrating a statistically significant reduction from baseline in trunk fat and an increase in total body lean mass at week 38 versus placebo. Safety results showed TransCon hGH appeared safe and well-tolerated, without discontinuations related to the study drug and a similar safety profile to daily hGH.2

“Our market research shows [lonapegsomatropin] is the treatment of choice for pediatric GHD among patients and physicians, and we are pleased to expand its availability in the United States for the treatment of adults initiating therapy or switching from another growth hormone therapy,” said Jan Mikkelsen, President and Chief Executive Officer at Ascendis Pharma.1 “This important milestone is the first of many planned label expansions supporting our goal to become the leading endocrinology rare disease company.”

According to the press release from Ascendis, the Company is on track to initiate basket trial for ISS, SHOX deficiency, Turner syndrome, and SGA, as well as combination therapy trials in achondroplasia and hypochondroplasia in Q4 2025.1

References

1. Ascendis Pharma. FDA Approves SKYTROFA® (Lonapegsomatropin-tcgd) for the Once-Weekly Treatment of Adults with Growth Hormone Deficiency. July 28, 2025. Accessed July 28, 2025. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-skytrofar-lonapegsomatropin-tcgd-once-weekly

2. Iapoce C. TransCon hGH Aims for FDA Label Expansion for Adult Growth Hormone Deficiency. September 30, 2024. Accessed July 28, 2025. https://www.hcplive.com/view/transcon-hgh-aims-for-fda-label-expansion-for-adult-growth-hormone-deficiency