Lonapegsomatropin (brand name Skytrofa, development name TransCon hGH) is a once-weekly form of human growth hormone (GH). It is a prodrug: ordinary somatropin, the same 22 kDa protein as daily GH injections, is temporarily attached to a large polyethylene glycol carrier. Under the skin the link breaks down on its own and releases unmodified somatropin over about a week (FDA label).

The FDA first approved it in 2021 for children with growth failure caused by GH deficiency (GHD). The label was updated in July 2025 to add a second indication: replacement of GH in adults with GHD (FDA label). Like all forms of GH, it is prohibited in sport at all times and is named on the WADA list (WADA 2026 Prohibited List).

This page summarizes what the FDA label, the phase 3 trials and regulators report. It is for education only and is not medical advice.

Property	Detail
Drug class	Long-acting growth hormone; prodrug of somatropin
Brand / approval	Skytrofa (Ascendis Pharma); FDA 2021 (children), adult GHD added July 2025; EU authorization January 2022 (children 3–18 years)
Route	Subcutaneous, once weekly, with the Skytrofa Auto-Injector
Strengths	14 cartridges, 0.7–13.3 mg (somatropin equivalents)
Labeled dose	Children: 0.24 mg/kg/week. Adults: start 0.7–2.1 mg/week, maximum 6.3 mg/week
Half-life (label)	≈30.7 h for the prodrug (children); ≈25 h apparent half-life for released somatropin
Structure	63 kDa conjugate: somatropin plus 4 × 10 kDa methoxy-PEG via a TransCon linker
US status	Prescription biologic; somatropin is not a controlled substance (label)
WADA status	Prohibited at all times, S2.2.3 (named)

What it is

Daily GH injections have been the standard treatment for GHD for decades. Ascendis Pharma designed lonapegsomatropin to reduce the burden of daily shots while still delivering the same, unmodified hormone. A 2017 review by the developers explains the approach: GH is bound to an inert methoxy polyethylene glycol (mPEG) carrier through a linker that hydrolyzes by itself (autohydrolysis) at normal body pH and temperature (Sprogøe et al., Endocr Connect 2017).

While it is attached, the large carrier keeps the molecule from being cleared quickly. Once the linker breaks, the released somatropin is identical to the GH in daily products. The carrier itself is cleared by the kidneys (FDA label).

This differs from long-acting GH products that modify the GH molecule itself, for example by enlarging it or adding albumin binding (Sprogøe et al., Endocr Connect 2017). Somapacitan (Sogroya), for example, is a GH analog with one amino-acid substitution and an attached side chain that binds albumin in the blood (Sogroya label). The broader biology of growth hormone, and the evidence on daily GH, is covered on the HGH page.

Feature	Lonapegsomatropin	Daily somatropin
Active hormone	Unmodified somatropin, released from a carrier	Unmodified somatropin
Molecular weight	63 kDa conjugate; 22 kDa once released	22 kDa
Dosing	Once weekly	Once daily

Once released, somatropin binds GH receptors on cells. Some effects are direct, such as fat breakdown (lipolysis) and increased glucose output by the liver. Others run through insulin-like growth factor-1 (IGF-1), which drives growth at the growth plates of long bones in children (FDA label).

Pharmacokinetics

The label reports the following steady-state values at the labeled pediatric dose and the maximum adult dose. Pediatric values are observed means; adult values are model-estimated medians (FDA label).

Measure	Children, 0.24 mg/kg/week	Adults, 6.3 mg/week
Prodrug peak (Cmax)	1,230 ng hGH/mL	69.3 ng hGH/mL
Prodrug time to peak	25 h	31 h
Released somatropin peak	15.2 ng/mL	2.47 ng/mL
Released somatropin time to peak	12 h	13 h
Somatropin exposure over one week (AUC)	500 h·ng/mL	75.4 h·ng/mL
mPEG carrier peak	13.1 mcg/mL at 36 h	4.60 mcg/mL at 34 h

Other points from the label:

Release. Somatropin is released by first-order autocleavage of the linker.
Half-life. The prodrug’s mean half-life in children was 30.7 h (±12.7). The apparent half-life of released somatropin was ≈25 h.
No buildup. No significant accumulation of the prodrug or somatropin was seen with repeat weekly dosing.
IGF-1 profile. At steady state, IGF-1 peaks ≈2 days after a dose, and the weekly average IGF-1 occurs ≈4.5 days after a dose. The adult label says to draw IGF-1 samples 4–5 days after the prior dose.
Dose response. In adults, a 1 mg/week dose change shifts the weekly average IGF-1 standard deviation score (SDS, distance from the age- and sex-matched mean) by 0.7 on average.
Elimination. Somatropin is broken down as a protein in the liver and kidneys; the mPEG carrier is cleared by the kidneys. No studies have been done in kidney or liver impairment.

In the first-in-human trial, 44 healthy men received a single dose of lonapegsomatropin (0.04–0.24 mg GH/kg), daily somatropin (Omnitrope) or placebo. GH peak levels and IGF-1 exposure were similar to equivalent doses of daily GH, and both rose in proportion to dose (Gilfoyle et al., Growth Horm IGF Res 2018).

Approved medical use

The current US label covers two indications (FDA label):

children 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of their own GH;
adults with GHD, as replacement of endogenous GH (added July 2025).

It is not indicated for children with growth failure due to genetically confirmed Prader-Willi syndrome. Before treatment, the label calls for an eye exam (fundoscopy) to exclude swelling of the optic disc (papilledema).

Labeled dosing

Population	Starting dose	Adjustment
Children (new to GH or switching)	0.24 mg/kg once weekly	Individualized by growth response
Adults 30–60 years, no oral estrogen	1.4 mg once weekly	Raised monthly by clinical response and/or IGF-1
Adults under 30, or any age on oral estrogen	2.1 mg once weekly	Same; maximum 6.3 mg/week
Adults over 60, no oral estrogen	0.7 mg once weekly	Same; maximum 6.3 mg/week

Women taking oral estrogen get a higher starting dose because oral estrogen blunts the IGF-1 response to GH. When switching from daily GH, the label says to wait at least 8 hours after the last daily dose; from another weekly GH product, at least 7 days (FDA label).

In the European Union, the medicine was authorized in January 2022 under the name Lonapegsomatropin Ascendis Pharma, later renamed Skytrofa. The EMA product page lists the indication as growth failure due to GHD in children and adolescents aged 3 to 18 years (EMA).

What the research shows

All of the controlled data come from people with GHD. There are no published trials of lonapegsomatropin for muscle, strength or performance in people with normal GH levels.

Children with GH deficiency: the heiGHt trial

The pivotal heiGHt trial randomized 161 treatment-naïve, prepubertal children with GHD (2:1) to weekly lonapegsomatropin or the same weekly dose of somatropin given daily, both at 0.24 mg/kg/week, for 52 weeks. It was open-label and ran at 73 sites in 15 countries (Thornton et al., JCEM 2021):

Outcome at 52 weeks	Lonapegsomatropin (n = 105)	Daily somatropin (n = 56)	Difference
Annualized height velocity	11.2 cm/year	10.3 cm/year	0.9 cm/year (95% CI 0.2–1.5)
Change in height SDS	+1.10	+0.96	P = 0.01

Weekly treatment met the noninferiority goal and was also statistically superior on height velocity. Bone age advancement, adverse events and antibody formation were similar between groups. Several of the authors were Ascendis Pharma employees.

Children: switching and long-term follow-up

fliGHt (switch study). In 146 children, 143 of whom had been on daily GH, switching to weekly lonapegsomatropin for 26 weeks gave a height velocity of 8.7 cm/year (95% CI 8.2–9.2). The adverse event profile was similar to that published for daily GH (Maniatis et al., Horm Res Paediatr 2022).
enliGHten, 2 years. In the open-label extension, children from heiGHt kept gaining relative height: height SDS rose from −2.89 to −1.37 by week 104 in those who started on lonapegsomatropin. Bone age did not advance faster than expected (Maniatis et al., JCEM 2022).
enliGHten, final results. With up to 6 years of treatment, mean height SDS reached −0.39 at year 4 (n = 298). Of 81 children who completed treatment in the trial, 48 (59.3%) met or exceeded their average parental height SDS. Mean weekly average IGF-1 stayed between 0 and 2 SDS (Maniatis et al., Horm Res Paediatr 2026).

The extension trials had no control group, so they show durability rather than a comparison with daily GH.

Adults with GH deficiency: the foresiGHt trial

The adult approval rests on foresiGHt, which randomized 259 adults with GHD 1:1:1 to weekly lonapegsomatropin, weekly placebo (double-blind) or open-label daily somatropin for 38 weeks. The primary endpoint was the change in trunk fat percentage measured by DXA scan (Biller et al., JCEM 2026; FDA label):

Change at 38 weeks	Lonapegsomatropin (n = 89)	Placebo (n = 84)	Difference (95% CI)
Trunk fat percentage	−1.7 points	+0.4 points	−2.0 (−2.9 to −1.1)
Total body lean mass	+1.6 kg	−0.1 kg	+1.7 kg (1.0 to 2.5)
Trunk fat mass	−0.5 kg	+0.2 kg	−0.7 kg (−1.2 to −0.2)
IGF-1 SDS at week 38 (baseline −2.6 vs −2.7)	1.4	−2.6	—

The daily somatropin arm had a trunk fat change of −3.1 points and reached a mean IGF-1 SDS of 0.49. The label notes that no formal statistical comparison was made between the weekly and daily arms, so the trial does not show whether one is better for body composition (FDA label).

In a 52-week open-label extension, 220 participants (88.7%) continued, all on lonapegsomatropin. Body composition gains were maintained for up to 90 weeks, and injection site reactions occurred in 5.1% (Biller et al., Endocr Pract 2026).

These results come from replacing a missing hormone in adults with GHD, not from adding GH on top of normal levels.

Earlier phase 2 trials

In 53 children with GHD, three weekly doses (0.14, 0.21 or 0.30 mg/kg/week) produced height velocities of 11.9–13.9 cm/year over 26 weeks, not statistically different from 11.6 cm/year with daily Genotropin (Chatelain et al., JCEM 2017).
In 37 adults with GHD treated for 4 weeks, GH peak levels and IGF-1 exposure were similar to daily GH at comparable doses, with no anti-GH antibodies detected (Höybye et al., Endocr Connect 2017).

Side effects and risks

Lonapegsomatropin carries no boxed warning. Its warnings are the class warnings shared by all somatropin products, plus lipoatrophy from repeated injections at one site (FDA label).

Common adverse reactions

Population (trial)	Adverse reaction	Lonapegsomatropin	Comparator
Children (heiGHt, vs daily GH)	Viral infection	15%	11%
Children	Fever	15%	9%
Children	Cough	11%	7%
Children	Nausea and vomiting	11%	7%
Children	Bleeding (mostly nosebleeds, bruising)	7%	2%
Children	Joint pain and arthritis	6%	2%
Adults (foresiGHt, vs placebo)	Edema (swelling)	8%	1%
Adults	Central hypothyroidism	7%	1%

Source: label Tables 2 and 3. In children, more patients shifted to high phosphate (44.2% vs 30.2%) and high alkaline phosphatase (19.2% vs 9.4%) than with daily GH. In adults, high alkaline phosphatase occurred in 14% vs 6% on placebo.

Blood sugar

GH lowers insulin sensitivity, especially at higher doses, and can unmask impaired glucose tolerance or type 2 diabetes. The label asks for glucose monitoring in all patients (FDA label). Case reports describe this with the weekly product:

a 12-year-old with obesity and prediabetes developed blood glucose of 500 mg/dL the day after his first dose and needed short-term insulin (Alkhatib et al., Horm Res Paediatr 2023);
a 13-year-old with obesity and hypopituitarism on hydrocortisone, with no prior glucose problems, developed diabetic ketoacidosis two days after the first dose; it resolved after GH was stopped (Mustafa et al., JCEM Case Rep 2026).

Case reports cannot show how often this happens, but they point to the first days after a weekly dose in high-risk patients.

Other labeled warnings

Acute critical illness. Pharmacologic doses of somatropin increased mortality in patients after open-heart or abdominal surgery, multiple trauma, or with acute respiratory failure. This is a contraindication.
Tumors. Contraindicated with active malignancy. Childhood cancer survivors treated with head radiation have a higher risk of a second tumor, mainly meningiomas.
Intracranial hypertension. Raised pressure in the skull with headache, vision changes and vomiting, usually within 8 weeks of starting and reversible on stopping.
Fluid retention. Edema, joint and muscle pain, and carpal tunnel syndrome; usually transient and dose dependent.
Adrenal and thyroid function. GH can lower cortisol and unmask central hypoadrenalism, and central hypothyroidism may appear or worsen.
Children. Slipped capital femoral epiphysis (a hip growth-plate injury), worsening scoliosis, and pancreatitis. Sudden deaths have occurred with somatropin in children with Prader-Willi syndrome who had severe obesity or breathing problems.
Hypersensitivity. Anaphylaxis and angioedema have been reported after marketing.
Overdose. Acute overdose can cause low then high blood sugar; long-term excess can cause signs of gigantism.

Who should not use it

The label lists these contraindications: acute critical illness, hypersensitivity to somatropin or the excipients, children with closed growth plates, active malignancy, active proliferative or severe non-proliferative diabetic retinopathy, and children with Prader-Willi syndrome who are severely obese or have severe breathing problems (FDA label).

Antibodies and the PEG carrier

Binding antibodies to the drug developed in 6.3% of 304 children and 5.7% of 247 adults in phase 3 trials. None were neutralizing, and they were not linked to side effects or loss of effect (FDA label).

The developers’ review notes that, in animals, repeated dosing of PEGylated proteins has sometimes caused vacuolation (small fluid-filled compartments) in scavenger cells and kidney tubule cells, without linked organ dysfunction in toxicology studies (Sprogøe et al., Endocr Connect 2017). This is animal data; long-term human safety data for the carrier come from the trials above. Carcinogenicity studies of lonapegsomatropin have not been done.

Interactions

Drug	Effect	Label guidance
Replacement glucocorticoids (especially cortisone acetate, prednisone)	GH inhibits the enzyme 11βHSD-1 that activates them, lowering cortisol	Higher maintenance or stress doses may be needed
High-dose glucocorticoids	May blunt growth response in children	Adjust carefully
Oral estrogen	Reduces IGF-1 response	Higher GH doses may be needed
Insulin and other diabetes drugs	GH lowers insulin sensitivity	Doses may need adjusting
CYP450-metabolized drugs	GH may increase their clearance	Monitor

Source: FDA label, section 7.

Pregnancy and breastfeeding

There are no human data with lonapegsomatropin in pregnancy. Decades of published data with somatropin have not identified a drug-related risk of birth defects or miscarriage, and rat studies at doses well above clinical exposure showed no fetal harm. There are no data on passage into breast milk (FDA label).

Monitoring

The label lists these checks during treatment:

What	When or why
Fundoscopic eye exam	Before starting, then periodically
Blood glucose	All patients; closely in those with diabetes or risk factors
Thyroid function	Periodically, as central hypothyroidism may emerge
Cortisol, glucocorticoid needs	In patients with or at risk of hypoadrenalism
IGF-1 (adults)	Drawn 4–5 days after the prior dose to guide monthly dose changes
Height velocity, hips, spine (children)	Poor growth, limp or hip/knee pain, scoliosis progression

Legal status and use outside medicine

In the US, Skytrofa is a prescription biologic. The label states that it is a prodrug of somatropin and that somatropin is not a controlled substance (FDA label). Separately, federal law makes it a crime to knowingly distribute human growth hormone for uses other than an FDA-authorized use ordered by a physician, with up to 5 years in prison (10 if a minor is involved). The statute defines human growth hormone as somatrem, somatropin or an analogue of either (21 U.S.C. 333).

In sport, the WADA 2026 list prohibits growth hormone, its analogues and fragments at all times, in and out of competition, as non-Specified Substances. Lonapegsomatropin is named as an example, alongside somapacitan and somatrogon (WADA 2026 Prohibited List).

No studies have tested it in healthy people beyond single-dose kinetics in the first-in-human trial.

Key takeaways

Weekly delivery of ordinary GH. Lonapegsomatropin is somatropin attached to a PEG carrier that releases the unmodified hormone over about a week.
Two FDA indications. It is approved for children with GH deficiency (since 2021) and, since July 2025, for adults with GH deficiency.
Strong data in GH-deficient patients. Children grew 11.2 vs 10.3 cm/year compared with daily GH; in adults, trunk fat fell 2.0 percentage points and lean mass rose 1.7 kg more than with placebo over 38 weeks.
Same risks as other GH. Fluid retention, high blood sugar, raised intracranial pressure and thyroid or adrenal changes apply; case reports describe severe hyperglycemia after the first weekly dose in high-risk children.
No evidence outside GH deficiency. There are no trials in people with normal GH levels, and it is banned in sport at all times.

Sources

Ascendis Pharma Endocrinology. Skytrofa (lonapegsomatropin-tcgd) for injection, prescribing information (indications updated July 2025). DailyMed.
European Medicines Agency. Skytrofa (previously Lonapegsomatropin Ascendis Pharma), EPAR. EMA.
Sprogøe K, Mortensen E, Karpf DB, Leff JA. The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency. Endocr Connect. 2017;6(8):R171–R181. PubMed.
Gilfoyle D, Mortensen E, Christoffersen ED, Leff JA, Beckert M. A first-in-man phase 1 trial for long-acting TransCon Growth Hormone. Growth Horm IGF Res. 2018;39:34–39. PubMed.
Chatelain P, Malievskiy O, Radziuk K, et al. A randomized phase 2 study of long-acting TransCon GH vs daily GH in childhood GH deficiency. J Clin Endocrinol Metab. 2017;102(5):1673–1682. PubMed.
Höybye C, Pfeiffer AF, Ferone D, et al. A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency. Endocr Connect. 2017;6(3):129–138. PubMed.
Thornton PS, Maniatis AK, Aghajanova E, 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. PubMed.
Maniatis AK, Nadgir U, Saenger P, 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. PubMed.
Maniatis AK, Casella SJ, Nadgir UM, 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. PubMed.
Maniatis AK, Thornton PS, Nadgir UM, 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. PubMed.
Biller BMK, Gilis-Januszewska A, Doknic M, 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. PubMed.
Biller BMK, Gilis-Januszewska A, Doknic M, et al. Long-term safety and efficacy of once-weekly lonapegsomatropin in adults with growth hormone deficiency: results from a 52-week open-label extension trial. Endocr Pract. Published online October 9, 2026. PubMed.
Alkhatib EH, Dauber A, Estrada DE, Majidi S. Weekly growth hormone (lonapegsomatropin) causes severe transient hyperglycemia in a child with obesity. Horm Res Paediatr. 2023;96(5):542–546. PubMed.
Mustafa M, Hannon TS, Fuqua JS. Diabetic ketoacidosis induced by long-acting growth hormone in a child without preexisting diabetes. JCEM Case Rep. 2026;4(8):luag198. PubMed.
Novo Nordisk. Sogroya (somapacitan-beco) injection, prescribing information. DailyMed.
21 U.S.C. 333(e), Prohibited distribution of human growth hormone. United States Code, 2023 edition. govinfo.
World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.

Lonapegsomatropin (Skytrofa)