Lonapegsomatropin
Somatropin on a releasable carrier, giving a week of growth hormone from one injection
Lonapegsomatropin is somatropin attached through a releasable linker to a polyethylene glycol carrier, so unmodified growth hormone is released over about a week. Ascendis's Skytrofa was first approved in the US in August 2021 for children with growth hormone deficiency, and its label now also covers adults.
What is it?
Unlike albumin-binding or fused weekly growth hormones, lonapegsomatropin releases ordinary somatropin. The hormone is attached to a 40 kDa polyethylene glycol carrier by a linker that breaks down at body temperature and pH, freeing unmodified growth hormone over the week; the label gives a half-life of about 30.7 hours in children.
In the pivotal heiGHt trial, treatment-naive children with growth hormone deficiency grew 11.2 cm a year on weekly lonapegsomatropin against 10.3 on daily somatropin, meeting non-inferiority and then superiority, the only weekly product here with a superiority result. In fliGHt, children switched from daily injections kept IGF-I up and preferred the weekly schedule.
The enliGHten extension followed these children for up to six years. Height SDS approached the average (-0.39 at year 4), 59.3% of those who completed treatment reached or passed their parents' average height, IGF-I stayed in range, and bone age did not run ahead.
Switching needs care in practice: at one centre, children moved from daily somatropin at close to the label dose saw IGF-I jump by 2.3 SDS, and five of 14 needed an immediate dose cut. Glucose deserves attention too; one report describes a 12-year-old with obesity and prediabetes whose blood sugar reached 500 mg/dL after a first dose.
In adults, the foresiGHt trial found less trunk fat (-1.68% against +0.37% on placebo) and more lean mass than placebo, and the label added adults with growth hormone deficiency in 2025, with starting doses set by age and estrogen use.
It is also being tested beyond growth hormone deficiency. In the phase 2 COACH trial in achondroplasia, adding it to navepegritide raised growth velocity to 8.69 cm a year against 5.95 with navepegritide alone in matched children, with better body proportions; that use is not on the label.
Its warnings are those of growth hormone, from intracranial hypertension to glucose intolerance, with the usual contraindication in acute critical illness. The most common effects in children were viral infections, fever, cough, nausea and vomiting.
It is one of three weekly growth hormones, alongside somapacitan and somatrogon; no head-to-head trial among them is carded here.
Mechanism of Action
Lonapegsomatropin is a prodrug: it carries ordinary somatropin and lets it go slowly.
TransCon carrier
Somatropin is linked to a 40 kDa methoxy-PEG carrier by a self-cleaving linker (dataset mechanism).
Unmodified hormone
The linker breaks down at body pH and temperature, releasing native somatropin into circulation (dataset mechanism).
Weekly profile
Half-life about 30.7 hours in children at 0.24 mg/kg a week (Skytrofa label 12.3).
Published Research
The trials behind lonapegsomatropin, read from their PubMed abstracts: heiGHt, fliGHt and the enliGHten extension in children, a clinic switching series, a case of severe hyperglycaemia, and the adult foresiGHt trial. Dosing from the Skytrofa label read October 1, 2026.
heiGHt: weekly against daily
In treatment-naive children with GHD, height velocity at 52 weeks was 11.2 cm a year on lonapegsomatropin against 10.3 on daily somatropin, showing non-inferiority and superiority; height SDS rose 1.10 against 0.96.
fliGHt: switching
Children switched from daily somatropin grew 8.7 cm a year at 26 weeks, kept IGF-I SDS about 0.7 above their pre-switch level, and children and parents preferred weekly dosing.
enliGHten: the extension
Over the long-term extension bone age advanced only minimally (bone age to chronological age ratio 0.8 at 104 weeks), the auto-injector caused fewer local reactions than syringes, and no new safety signals appeared.
enliGHten: up to six years
In the long-term extension of heiGHt and fliGHt, mean height SDS reached -0.39 at year 4 (298 children); of 81 who completed treatment, 48 (59.3%) met or exceeded their average parental height, and weekly average IGF-I stayed between 0 and 2 SDS without accelerated bone maturation.
Switching in clinic
In 14 children switched from daily somatropin at one centre, starting lonapegsomatropin at a median 0.23 mg/kg a week raised IGF-I by 2.3 SDS; five needed an immediate dose reduction and four of them further adjustment, with no serious adverse effects.
Case report: severe high blood sugar
A 12-year-old with obesity and prediabetes on metformin developed blood glucose of 500 mg/dL the day after his first 0.25 mg/kg dose; it resolved with brief insulin treatment and weekly growth hormone was stopped.
foresiGHt: adults
In adults with GHD, lonapegsomatropin cut trunk fat percentage (-1.68% against +0.37% on placebo) and raised lean mass (+1.60 against -0.11 kg), meeting its primary endpoint, with safety comparable to somatropin.
COACH: with navepegritide in achondroplasia
In 21 children aged 2 to 11 with achondroplasia, weekly navepegritide plus lonapegsomatropin gave treatment-naive children a growth velocity of 8.69 cm a year at 52 weeks against 5.95 for matched children on navepegritide alone, with better body proportions and mostly mild adverse events. Achondroplasia is not on its label.
First approval
A drug review recording its first approval, in the US in August 2021, for children at least 1 year old and 11.5 kg with growth failure from GH deficiency, given as a weekly injection.
Dosing Data
Dosed by label once weekly; adult doses start by age and oral estrogen use and are titrated monthly to response and IGF-1.
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Side Effects & Contraindications
Reported Side Effects
From the Skytrofa label (version 13).
Contraindications & Cautions
From the label.
Legal Status
Approved in the US for children and adults.
Frequently Asked Questions
?What does 'transiently PEGylated' mean?
The growth hormone is attached to its carrier by a linker that breaks down in the body, releasing unmodified somatropin over the week.
?How long does it last?
The label reports a mean half-life of about 30.7 hours in children at 0.24 mg/kg a week.
?Which weekly growth hormone is best?
There is no head-to-head trial among them here; lonapegsomatropin's pivotal trial is the one that showed superiority over daily somatropin.
?Is it approved for adults?
Yes: the US label added adults with growth hormone deficiency in 2025, after the foresiGHt trial.
?What happens long term in children?
In the enliGHten extension, height SDS approached average and 59.3% of children who completed treatment reached or passed their average parental height.
?Is switching from daily growth hormone straightforward?
Not always: at one centre IGF-I rose by 2.3 SDS after switching, and five of 14 children needed an immediate dose reduction.
?Can it raise blood sugar?
Growth hormone can impair glucose tolerance, and a case report describes severe high blood sugar after a first dose in a child with obesity and prediabetes.
?Who makes it?
Ascendis Pharma, as Skytrofa, first approved in the US in August 2021.
?Is it used for achondroplasia?
Not under its label. In the phase 2 COACH trial, adding it to navepegritide in 21 children raised growth velocity above that seen with navepegritide alone.
References
- [fda-pi] Skytrofa (lonapegsomatropin-tcgd) for injection US prescribing information (DailyMed version 13, effective July 23, 2026); read October 1, 2026.
- [clinical-trial] Thornton PS, et al. "Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial." J Clin Endocrinol Metab, 2021;106(11):3184-3195. PMID: 34272849.
- [clinical-trial] Maniatis AK, et al. "Switching to Weekly Lonapegsomatropin from Daily Somatropin in Children with Growth Hormone Deficiency: The fliGHt Trial." Horm Res Paediatr, 2022;95(3):233-243. PMID: 35263755.
- [clinical-trial] Maniatis AK, et al. "Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results." J Clin Endocrinol Metab, 2022;107(7):e2680-e2689. PMID: 35428884.
- [clinical-trial] Biller BMK, et al. "Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results." J Clin Endocrinol Metab, 2026;111(6):1640-1650. PMID: 41420532.
- [review] Lamb YN. "Lonapegsomatropin: Pediatric First Approval." Paediatr Drugs, 2022;24(1):83-90. PMID: 34709591.
- [pubmed] Maniatis AK, et al. "Children with Growth Hormone Deficiency Treated with Lonapegsomatropin Demonstrated Sustained Height Improvements for up to 6 Years: enliGHten Trial Final Results." Horm Res Paediatr, 2026;99(5):705-717. PMID: 40049149.
- [pubmed] Coyne E, et al. "Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency." J Pediatr Endocrinol Metab, 2025;38(3):248-253. PMID: 39843388.
- [pubmed] Alkhatib EH, et al. "Weekly Growth Hormone (Lonapegsomatropin) Causes Severe Transient Hyperglycemia in a Child with Obesity." Horm Res Paediatr, 2023;96(5):542-546. PMID: 37015214.
- [clinical-trial] McDonnell CM, et al. "Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial." Eur J Endocrinol, 2026;194(6):745-755. PMID: 42144862.
Sources & Citations
Dosing and warnings from the Skytrofa label (DailyMed version 13, effective July 23, 2026, read October 1, 2026); approvals from Drugs@FDA; studies from PubMed abstracts.
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