Lonapegsomatropin-Tcgd Receives FDA Approval for Growth Hormone Deficiency

The FDA has approved lonapegsomatropin-tcgd (Skyrofa; Ascendis Pharma), a prodrug of somatropin, a human growth hormone administered once weekly for the replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD), a rare disorder that is caused by a decreased or total loss of growth hormone deficiency.¹

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“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,” Kevin Yuen, MD, Barrow Neurological Institute, University of Arizona College of Medicine, and Creighton University School of Medicine in Phoenix, Arizona, said in a news release.¹

Growth Hormone Deficiency

As a rare condition, GHD occurs when the pituitary gland does not release enough growth hormone, affecting about 1 in 4000 to 10,000 infants and children and nearly 1 in every 10,000 adults. Growth hormones promote growth in children and are crucial for normal growth, muscle, bone strength, and distribution of body fat; however, once the growth plates in the bones have fused, growth hormones do not continue to increase height but are still needed in the body to help maintain normal body structure and metabolism and keep glucose levels in a healthy range. If an individual does not have enough growth hormone, it can impact various factors, including normal growth in infants and children and increased body fat and blood sugar levels in adults.²

The main sign of GHD in infants and children is slow height growth each year after the third birthday, insinuating less than 1.4 inches of growth each year. Other symptoms include a younger-looking face than expected at a certain age, impaired hair and nail growth, delayed tooth development, delayed puberty, and hypoglycemia. Symptoms of adult-onset GHD are harder to pinpoint and can include a reduced sense of well-being, anxiety, depression, decreased energy levels, increased body fat, decreased muscle tone, decreased bone density, insulin resistance, and an increase in low-density lipoprotein–cholesterol and triglyceride levels.²

Treatment for GHD involves an at-home, daily synthetic growth hormone injection, which is reported to cause mild to moderate adverse effects (AEs), including headaches, muscle or joint pain, underactive thyroid gland, and progression of spine curvature in individuals with scoliosis. In some cases, individuals can experience more serious but rare AEs like severe headaches with vision problems, hip dysplasia, and pancreatitis.²

“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,” Yuen said in the news release.¹

Clinical Trial Support

The approval is based on results from the randomized, parallel-arm, placebo-controlled, double-blind, active-controlled, open-label phase 3 clinical trial that assessed the safety and efficacy of weekly lonapegsomatropin with weekly placebo and daily somatropin in adults with GHD.¹

Results from the study demonstrated the most common AEs of lonapegsomatropin in children include viral infection, fever, cough, nausea, vomiting, bleeding, diarrhea, stomach area pain, joint pain, and arthritis. The most common AEs in adults include swelling caused by fluid buildup and low thyroid hormone.¹

With the approval, lonapegsomatropin is indicated as a replacement of growth hormone in children 1 year or older who weigh at least 26 pounds with GHD, along with adults with GHD.¹

“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,” Jan Mikkelsen, president and CEO at Ascendis Pharma, said in the news release. “This important milestone is the first of many planned label expansions supporting our goal to become the leading endocrinology rare disease company.”¹

REFERENCES

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

2. Cleveland Clinic. Growth Hormone Deficiency (GHD). News release. July 21, 2022. Accessed July 28, 2025. https://my.clevelandclinic.org/health/diseases/23343-growth-hormone-deficiency-ghd