LAS VEGAS — Lonapegsomatropin (Skytrofa, Ascendis Pharma), a prodrug of somatropin injected once weekly, designed to provide sustained release of active, unmodified somatropin, provides long-term efficacy and safety in adults with growth hormone deficiency (GHD), new data from a 52-week open-label extension of the foresiGHt trial showed. 

“We were very pleased to see that adults with GH deficiency who were treated long-term with once-weekly lonapegsomatropin maintained favorable body composition, with reduced trunk fat and visceral adipose tissue, and increased total and trunk lean mass,”

said Julie M Silverstein, MD, medical director of the Pituitary Center and professor of medicine and neurological surgery at Washington University School of Medicine, St Louis, who presented the results here at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026.

The once-weekly formulation is an important feature, Silverstein told Medscape Medical News. “Current guidelines state that the frequency of daily GH injections is thought to be one of the major factors contributing to nonadherence…Suboptimal adherence and persistence to daily somatropin has been associated with less favorable clinical outcomes, underscoring the need for less burdensome treatments,” she explained.

Lonapegsomatropin was previously approved in the US and in the EU for pediatric GHD, and approved last year in the US for adults with GHD based on the 38-week data from the trial.

These extension results confirm those previously reported, said Silverstein. “And once-weekly lonapegsomatropin remained well-tolerated, with low discontinuation rates and few injection-site reactions, and no new safety signals observed with longer-term use.”

Ongoing Benefit After a Year 

In the foresiGHt trial, 259 adults with GHD were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. A total of 220 participants continued into the 52-week extension trial, and the two groups not initially using once-weekly lonapegsomatropin were switched to it. Those who had been on lonapegsomatropin were retitrated.

The etiology of GHD was hypothalamic-pituitary surgery in 37%, pituitary tumor in 30%, and structural hypothalamic-pituitary defect in 18%. Less common causes included genetic and cranial irradiation, while 14% were idiopathic. 

Across the entire 90-week study plus extension, treatment-emergent adverse events occurring in 5% or more of study participants were nasopharyngitis in 9.7%, upper respiratory tract infection in 9.3%, headache in 8.1%, COVID-19 in 7.2%, arthralgia in 6.4%, and injection site reactions in 5.1%. Most adverse events were mild to moderate, and just 3.8% discontinued due to adverse events, Silverstein reported. 

The incidence of treatment-emergent antibodies was 3.4% for anti-human growth hormone and anti-lonapegsomatropin antibodies, and 0.9% for anti-polyethylene glycol binding antibodies. No neutralizing antibodies were detected. 

For the study participants who continued lonapegsomatropin or switched to lonapegsomatropin from somatropin after completing foresiGHt, trunk percent fat and trunk fat mass slightly increased during the re-titration period but remained relatively stable during dose maintenance. Both of those parameters decreased over 52 weeks in those who switched from placebo. 

Total body lean mass slightly decreased during retitration and increased during dose maintenance in participants who continued lonapegsomatropin or switched from somatropin, while those who switched from placebo showed an overall increase during the extension, Silverstein said. 

Weekly average insulin-like growth factor 1 levels had normalized in both the two active treatment groups during the original study and in the former placebo group during the extension through week 90. A1c levels remained stable throughout, and there were no new diabetes diagnoses. 

Scores on the treatment-related impact measure-adult GHD scale — an assessment of patient quality of life, treatment satisfaction, and symptom burden — were consistent in the three groups at week 90. Score drops from baseline of 21.5, 19.4, and 22.7 were seen in the initial lonapegsomatropin, placebo, and somatropin groups, respectively, indicating a reduced burden of GH deficiency. 

Silverstein told Medscape that lonapegsomatropin may be considered by patients who are looking for a long-acting GH treatment that delivers the identical somatropin as a daily GH in a preservative-free formula. It may also be considered “by patients for whom room-temperature storage is important, and those who prefer exact-dose delivery with no dose dialing or potential for multiple or split injections, with no drug wasted.”

Asked to comment, session moderator Lance A. Sloan, MD, president of the Texas Institute for Kidney and Endocrine Disorders, Lufkin, told Medscape Medical News, “I think it's reassuring to have longer term data. There were no surprises.”

Silverstein has received consulting fees from Xeris and Chiesi, served on advisory boards for Camurus, and served as a research investigator for Ascendis Pharma, Fractyl Health, Camurus, Bayer, Sparrow, Recordati, and AbbVie. Sloan has served as a clinical investigator, consultant, and/or speaker for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Eli Lilly, GSK, Janssen, Merck, Novo Nordisk, Pfizer, and Sanofi. 

Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and DiaTribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social