Introduction
Ngenla (somatrogon-ghla) is a long-acting recombinant human growth hormone approved by the FDA in June 2023 for the treatment of pediatric growth hormone deficiency. It represents a significant advancement in growth hormone therapy as the first once-weekly product in this class, offering improved convenience and potentially better adherence compared to daily growth hormone formulations.
Mechanism of Action
Ngenla is a glycoprotein hormone consisting of 191 amino acids with the same amino acid sequence as endogenous human growth hormone, but with the addition of a C-terminal peptide (CTP) from human chorionic gonadotropin. This modification extends the molecule's half-life by reducing renal clearance and delaying metabolic degradation. Like endogenous growth hormone, Ngenla binds to growth hormone receptors, stimulating hepatic production of insulin-like growth factor-1 (IGF-1), which mediates many of growth hormone's anabolic and growth-promoting effects.
Indications
Ngenla is indicated for the treatment of pediatric patients aged 3 years and older who have growth failure due to inadequate secretion of endogenous growth hormone. It is approved for both growth hormone deficiency and those with growth failure associated with other conditions where growth hormone therapy is appropriate.
Dosage and Administration
The recommended dosage is 0.66 mg/kg administered once weekly by subcutaneous injection. The injection can be administered in the abdomen, thigh, buttocks, or upper arm, with rotation of injection sites. Dosing should be individualized based on growth response and IGF-1 levels. No dosage adjustment is required for renal or hepatic impairment. The product is supplied as a prefilled pen containing 24 mg/1.5 mL or 60 mg/1.5 mL.
Pharmacokinetics
Absorption: Following subcutaneous administration, Ngenla demonstrates prolonged absorption with a median Tmax of approximately 16-20 hours. Distribution: Volume of distribution is approximately 50-60 L. Protein binding is not characterized due to specific binding to growth hormone receptors. Metabolism: Undergoes proteolytic metabolism primarily in the liver and kidneys via lysosomal degradation. Elimination: Terminal half-life is approximately 34-38 hours, significantly longer than daily growth hormone products (3-4 hours). Clearance occurs primarily through renal pathways.Contraindications
- Hypersensitivity to somatrogon-ghla or any component of the formulation
- Active malignancy
- Active proliferative or severe non-proliferative diabetic retinopathy
- Acute critical illness due to complications following open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure
- Pediatric patients with closed epiphyses
Warnings and Precautions
Neoplasms: Increased risk of second neoplasms in childhood cancer survivors. Monitor patients with preexisting tumors for progression or recurrence. Glucose intolerance: May decrease insulin sensitivity. Monitor glucose levels periodically. Intracranial hypertension: Has been reported with growth hormone therapy. Perform fundoscopic examination if symptoms occur. Fluid retention: May cause edema, arthralgia, and carpal tunnel syndrome, especially during initial treatment. Hypothyroidism: May exacerbate preexisting hypothyroidism. Monitor thyroid function periodically. Slipped capital femoral epiphysis: Evaluate children with onset of limp or hip/knee pain. Pancreatitis: Has been reported with growth hormone products.Drug Interactions
Glucocorticoids: May inhibit growth promotion. Adjust glucocorticoid replacement to physiologic levels. Cytochrome P450-metabolized drugs: Growth hormone may alter the clearance of these medications. Monitor appropriately. Oral estrogen: May reduce serum IGF-1 response to Ngenla. Insulin and oral hypoglycemics: May require adjustment of antidiabetic medications.Adverse Effects
Common (≥10%): Injection site reactions, headache, pyrexia, anemia, vomiting, hypothyroidism Serious: Intracranial hypertension, slipped capital femoral epiphysis, scoliosis progression, severe hypersensitivity reactions, pancreatitis, neoplasmsMonitoring Parameters
- Height and growth velocity every 3-6 months
- IGF-1 levels at treatment initiation and periodically thereafter
- Thyroid function tests annually
- Fundoscopic examination if symptoms of intracranial hypertension occur
- Blood glucose monitoring, especially in patients with risk factors for diabetes
- Assessment for scoliosis in patients with rapid growth
Patient Education
- Administer once weekly on the same day each week
- Rotate injection sites to prevent lipoatrophy
- Proper injection technique training is essential
- Report any signs of injection site reactions, severe headaches, visual changes, or limping
- Do not share pens between patients
- Store refrigerated at 2°C to 8°C; do not freeze
- Discard pen 6 weeks after first use
References
1. FDA Prescribing Information: Ngenla (somatrogon-ghla). June 2023. 2. ClinicalTrials.gov: NCT03290235. A Study of Somatrogon in Children With Growth Hormone Deficiency. 3. Hou L, Chen SH, Wang J, et al. Pharmacokinetics and pharmacodynamics of a novel long-acting human growth hormone fusion protein in growth hormone deficient adults. Growth Horm IGF Res. 2021;58:101390. 4. Deal CL, Tony M, Höybye C, et al. Growth Hormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab. 2023;108(2):259-271. 5. Clemmons DR. Long-acting growth hormone for the treatment of growth hormone deficiency. Curr Opin Endocrinol Diabetes Obes. 2022;29(1):79-85.