PIVOTAL clinical trials| SKYTROFA® (lonapegsomatropin-tcgd)
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SKYTROFA® is also FDA approved for adults with growth hormone deficiency
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SKYTROFA has been studied in treatment-naïve and -experienced children with GHD, totaling more than 300 patients1-3

SKYTROFA phase 3 program in pediatric GHD1-4

heiGHt trial logo
Pivotal Data

Supportive trials in switch patients as well as long-term follow-up of participating patients, with up to 6 years of data

  • heiGHt: A 52-week, randomized, open-label, active-controlled, parallel-group phase 3 study of 161 treatment-naïve, prepubertal (Tanner stage I) pediatric patients with GHD aged 3 years and older. Patients were randomized in a 2:1 ratio to receive either SKYTROFA 0.24 mg/kg/week (n = 105) or daily somatropin using Genotropin® 0.24 mg/kg/week (n = 56). The primary endpoint was AHV at 52 weeks.1,2
  • fliGHt: A 26-week open-label, single-arm trial of children with GHD who switched to SKYTROFA after having been treated with daily somatropin for ≤130 weeks(n = 143).3 See Full Study Design
  • enliGHten: Long-term open-label extension trial of children with GHD who completed the heiGHt (n = 158) and fliGHt (n = 140) trials (N = 298). Mean duration of treatment was 3.5 years (maximum 5 years).4,5 See Full Study Design
Treatment-naïve patients

Increased growth with fewer injections1

SKYTROFA demonstrated higher mean AHV versus daily somatropin1,2

Mean AHV* at week 52: once-weekly SKYTROFA versus daily somatropin1,2

Increased growth chart photo

The treatment difference in AHV with SKYTROFA compared with daily somatropin at week 52 (11.2 cm/year versus 10.3 cm/year, respectively) was 0.9 cm/year (95% CI: 0.2 to 1.5 cm/year)1,2

See Full Study Design See Patient Demographics
  • *LS mean by ANCOVA.2
Treatment-naïve patients

Height SDS, change from baseline, over 52 weeks

Higher height SDS change from baseline across 52 weeks2,6

height SDS chart image

At week 52, SKYTROFA had a greater increase from baseline in height SDS compared with daily somatropin: 1.10 versus 0.96 from baseline of –2.9 and –3.0, respectively1

  • Study limitations: Height SDS at weeks 13, 26, and 39 are additional endpoints of the pivotal heiGHt trial, which was not powered to evaluate the differences observed. Data should be interpreted with caution; no conclusions can be drawn.
See Full Study Design
Treatment-naïve patients

Bone age and BMI data

Bone age: chronological age ratio BMI SDS

Bone age-to-chronological age ratio at baseline and week 522

Mean BMI SDS at baseline and week 522

bone age chart photo

Study limitations: Bone age and BMI were additional secondary endpoints of the trial and not powered to evaluate the differences observed. No formal statistical comparison was made. Data should be interpreted with caution; no conclusions can be drawn.

Bone age-to-chronological age ratio was similar with SKYTROFA and daily somatropin at baseline and advanced similarly for both groups at week 522
See Full Study Design
BMI SDS chart photo

Study limitations: Bone age and BMI were additional secondary endpoints of the trial and not powered to evaluate the differences observed. No formal statistical comparison was made. Data should be interpreted with caution; no conclusions can be drawn.

Observed changes in mean BMI SDS remained within the normal range (± 2.0 SD of the mean) for both groups2
See Full Study Design

Study design

A 52-week, randomized, open-label, active-controlled, parallel-group phase 3 study of 161 treatment-naïve, prepubertal (Tanner stage I) pediatric patients with GHD aged 3 years and older. Patients were randomized in a 2:1 ratio to receive either SKYTROFA 0.24 mg/kg/week (n = 105) or daily somatropin using Genotropin® 0.24 mg/kg/week (n = 56). The primary endpoint was AHV at 52 weeks.1,2

AHV = annualized height velocity; GHD = growth hormone deficiency.

Patient demographics in heiGHt2*

Baseline demographics and
clinical characteristics		 SKYTROFA
0.24 mg/kg/week		 Daily somatropin†
0.24 mg/kg/week		 Total
(n = 105) (n = 56) (N = 161)
Male, n (%) 86 (82) 46 (82) 132 (82)
White, n (%) 100 (95.2) 52 (92.9) 152 (94.4)
Chronological age (year) 8.5 ± 2.7 8.5 ± 2.8 8.5 ± 2.7
Bone age (year) 5.8 ± 2.6 6.0 ± 2.7 5.9 ± 2.6
Bone age/chronological age (ratio) 0.69 ± 0.16 0.70 ± 0.14 0.69 ± 0.15
Weight (kg) 21.0 ± 6.5 21.2 ± 6.7 21.1 ± 6.6
BMI (kg/m>2) 16.1 ± 1.8 16.5 ± 2.2 16.2 ± 1.9
Height (cm) 112.9 ± 14.1 112.2 ± 15.3 112.7 ± 14.5
Height (SDS) -2.89 ± 0.85 -3.00 ± 0.90 -2.93 ± 0.87
Historical growth rate (cm/year)‡ 3.9 ± 2.0 3.9 ± 1.7 3.9 ± 1.9
IGF-1 SDS -2.08 ± 0.88 -1.96 ± 0.98 -2.04 ± 0.92
  • *Plus-minus values are means ± SD.
  • †Genotropin.
  • ‡Historical growth rates based on best available medical records (SKYTROFA [n = 94] and daily somatropin [n = 54]).

BMI = body mass index; IGF-1 = insulin-like growth factor 1; SDS = standard deviation score.

Study design

A multicenter, phase 3, open-label, single arm, 26-week trial investigating the safety, tolerability, and efficacy of SKYTROFA administered once weekly in children with GHD. The trial included 3 treatment-naïve and 143 treatment-experienced patients previously treated with daily somatropin for ≤ 130 weeks. The mean daily somatropin dose was 0.29 mg/kg/week upon entering the trial. Safety and tolerability were the primary endpoints. Patients aged 6 months to 3 years could be treatment naïve and were included only in the safety and tolerability analyses.3

GHD = Growth Hormone Deficiency

Patient demographics in fliGHt3: A broad range of pediatric patients enrolled in the 26-week clinical trial

Baseline demographics and
clinical characteristics		 Total enrolled Previously treated
N = 146 n = 143
Male, n (%) 110 (75.3) 109 (76.2)
White, n (%) 124 (84.9) 121 (84.6)
Hispanic or Latino, n (%) 10 (6.8) 10 (7.0)
Mean chronological age (year) 10.6 10.8
BMI SDS, mean (SD) –0.3 (1.1) –0.24 (1.06)
Height SDS, mean (SD) –1.42 (0.84) –1.40 (0.83)
Tanner stage, n (%)
I 95 (65.1) 92 (64.3)
II 14 (9.6) 14 (9.8)
III 30 (20.5) 30 (21.0)
IV 7 (4.8) 7 (4.9)
IGF‑1 SDS, mean (SD) 0.85 (1.29) 0.91 (1.25)
Daily somatropin dose at trial enrollment (mg hGH/kg/week) n/a 0.29 (0.05)
Daily somatropin dose duration since treatment initiation (years) n/a 1.14 (0.73)

BMI = body mass index; hGH = human growth hormone; IGF-1 = insulin-like growth factor 1; SD = standard deviation; SDS = standard deviation score.

Study design

An open-label extension study of pediatric patients with GHD who had previously participated in phase 3 SKYTROFA trials, heiGHt (n = 158) or fliGHt (n = 140) (N = 298). The mean age at baseline of the enliGHten trial was 10.3 years. At the start of enliGHten trial, patients either received SKYTROFA 0.24 mg/kg/week or the most recent dose they received in the earlier study. Long-term safety was the primary endpoint.4,5

GHD = growth hormone deficiency.

Patient demographics in enliGHten4

Patients from the heiGHt (n = 158) and fliGHt (n = 140) trials continued into the enliGHten open-label extension4,5

Baseline demographics and
clinical characteristics		 Full analysis set* Treatment completers†
(N = 298) (n = 81)
Age, years, mean (SD) 10.3 (3.4) 13.3 (1.8)
Sex, male, n (%) 235 (78.9) 66 (81.5)
Height SDS, mean (SD) –1.6 (0.9) –1.6 (0.7)
IGF‑1 SDS, mean (SD) 1.0 (1.3) 0.8 (1.5)
Tanner stage, n (%)
I 214 (71.8) 22 (30.1)
II 40 (13.4) 17 (23.3)
III 25 (8.4) 28 (38.4)
IV 16 (5.4) 6 (8.2)
V 3 (1.0) 0
  • *All participants who signed informed consent for the extension trial and received at least one dose of SKYTROFA.
  • †A subset of patients (n = 81) who completed SKYTROFA treatment because it was determined by the physician that treatment for pediatric GHD was no longer necessary.

GHD = growth hormone deficiency; IGF-1 = insulin-like growth factor-1; SD = standard deviation; SDS = standard deviation score.

IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

SKYTROFA® (lonapegsomatropin-tcgd) injection is a human growth hormone (GH) indicated for the:

  • Treatment of pediatric patients aged 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous GH
  • Replacement of endogenous GH in adults with growth hormone deficiency (GHD)

CONTRAINDICATIONS

SKYTROFA is contraindicated in patients with:

  • Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to risk of increased mortality with use of somatropin
  • Hypersensitivity to somatropin or any of the excipients in SKYTROFA
  • Pediatric patients with closed epiphyses
  • Active malignancy
  • Active proliferative or severe non-proliferative diabetic retinopathy
  • Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death

WARNINGS AND PRECAUTIONS

  • Increased Mortality in Patients with Acute Critical Illness: Increased mortality has been reported after treatment with somatropin in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery, multiple accidental trauma, and in patients with acute respiratory failure
  • Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylaxis and angioedema have been reported with post-marketing use of somatropin products, including SKYTROFA. Inform patients and/or caregivers that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs
  • Increased Risk of Neoplasms: There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy. Any preexisting malignancy should be inactive, and its treatment complete prior to instituting SKYTROFA. In childhood cancer survivors treated with radiation to the brain/head for their first neoplasm who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Children with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients with a history of GHD secondary to an intracranial neoplasm for progression/recurrence of the tumor. Monitor patients carefully for development of neoplasms and/or increased growth/potential malignant changes of preexisting nevi. Advise patients/caregivers to report changes in the appearance of preexisting nevi
  • Glucose Intolerance and Diabetes Mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. Previously undiagnosed impaired glucose tolerance and overt type 2 diabetes mellitus may be unmasked. Monitor glucose levels in all patients, especially those with risk factors for type 2 diabetes mellitus, such as obesity or a family history of type 2 diabetes mellitus. When initiating SKYTROFA, monitor patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance closely, and adjust the doses of antihyperglycemic drugs as needed
  • Intracranial Hypertension: Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin. Symptoms usually occurred within 8 weeks of the initiation of somatropin and resolved rapidly after cessation of therapy/reduction of the dose. Perform fundoscopic examination prior to initiation of treatment and periodically thereafter. If papilledema is observed, stop the treatment. If somatropin-induced IH is confirmed, restart SKYTROFA treatment at a lower dose after IH-associated signs and symptoms have resolved
  • Fluid Retention: May occur during somatropin therapy. Clinical manifestations of fluid retention (eg, edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent
  • Hypoadrenalism: Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance/stress doses following initiation of SKYTROFA therapy. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases
  • Hypothyroidism: Undiagnosed/untreated hypothyroidism may prevent an optimal response to SKYTROFA. Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of SKYTROFA
  • Slipped Capital Femoral Epiphysis in Pediatric Patients: Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth and may lead to osteonecrosis. Evaluate pediatric patients receiving SKYTROFA with the onset of a limp or complaints of persistent hip or knee pain for slipped capital femoral epiphysis and osteonecrosis, and manage accordingly
  • Progression of Preexisting Scoliosis in Pediatric Patients: Monitor patients with a history of scoliosis for disease progression
  • Pancreatitis: Cases of pancreatitis have been reported in pediatric patients receiving somatropin. The risk may be greater in pediatric patients than in adults. Consider pancreatitis in patients with persistent severe abdominal pain
  • Lipoatrophy: Lipoatrophy may result when somatropin is administered at the same site over a long period of time. Rotate injection sites to reduce this risk
  • Sudden Death in Pediatric Patients With Prader-Willi Syndrome: There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than female patients. SKYTROFA is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome
  • Laboratory Tests: Serum levels of alkaline phosphatase and phosphate may increase after SKYTROFA therapy. Serum levels of parathyroid hormone may increase after somatropin treatment. If a patient is found to have abnormal laboratory tests, monitor as appropriate

ADVERSE REACTIONS

  • Pediatric patients with GHD: the most common adverse reactions (≥ 5%) in patients treated with SKYTROFA and more frequently than in those treated with daily somatropin were viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis
  • Adult patients with GHD: the most common adverse reaction (≥ 5%) in patients treated with SKYTROFA and more frequently than in those treated with placebo were edema and central (secondary) hypothyroidism

DRUG INTERACTIONS

  • Glucocorticoids: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SKYTROFA
  • Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth
  • Cytochrome P450-Metabolized Drugs: SKYTROFA may alter the clearance. Monitor carefully if used with SKYTROFA
  • Oral Estrogen: Patients receiving oral estrogen replacement may require higher SKYTROFA dosages
  • Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin and/or antihyperglycemic agent may be required for patients with diabetes mellitus

You are encouraged to report side effects to FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Ascendis Pharma at 1-844-442-7236.

Please click here for SKYTROFA full Prescribing Information.

References: 1. SKYTROFA. Prescribing information. Ascendis Pharma Endocrinology, Inc.; 2025. 2. 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. doi:10.1210/clinem/dgab529 3. 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. doi:10.1159/000524003 4. 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. [Published online March 6, 2025.] doi:10.1159/000545064 5. 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. doi:10.1210/clinem/dgac217 6. Ascendis Pharma Endocrinology, Inc. Data on file; 2020.

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