Prader-Willi Syndrome (PWS)

Somatropin (sold as Genotropin^®, Norditropin^®, and Omnitrope^®, among others) is a recombinant human growth hormone indicated for the treatment of Prader-Willi syndrome (PWS).¹ As a result of complex hypothalamic involvement in PWS, there is disruption of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis.² However, somatropin, or human growth hormone (HGH), has been shown to be advantageous for people with PWS in numerous trials. Therapy with somatropin can improve muscle strength, linear growth, psychomotor development, metabolic condition, cognition, and health-related quality of life.^1,2 

Somatropin is not advised for individuals with uncontrolled diabetes, active cancer, or acute critical sickness. It is recommended for patients with PWS to start therapy with somatropin between the ages of 3 and 6 months, or as early as date of diagnosis.³ Patients who receive treatment while still young can grow to their expected final adult height.²

The US Food and Drug Administration (FDA) approved HGH therapy for the treatment of children with PWS, adding indications for PWS to Genotropin, Omnitrope, and Norditropin, beginning with the approval of Genotropin in 2000.^1,4,5

Mechanism of Action

Somatropin is a polypeptide hormone of recombinant DNA origin.^4-9 Treatment with somatropin mimics and restores the actions of endogenous GH, which include stimulating linear bone growth, improving bone mass, increasing muscle mass, and decreasing fat mass. It also helps control blood glucose and lipid levels in the presence of growth failure, GH deficiency, low body mass, and/or malnutrition.⁹ 

Read more about PWS pathophysiology

Somatropin takes effect directly and also indirectly through IGF-1, which is upregulated by GH. It interacts with target cells in the liver and cartilage that express the dimeric human GH receptor (GHR). GH binds to the GHR, which dimerizes and interacts with Janus kinase 2 (JAK2), causing JAK2 and the GHR to be tyrosine phosphorylated. The signal transducer activator of transcription (STAT) pathway is activated, causing the translocation of transcription factors, including STAT1, STAT3, and STAT5, into the nucleus to promote the transcription of the target gene. GH stimulates linear growth at the epiphysis, or growth plate, by encouraging prechondrocyte differentiation and osteoblast expansion.⁹ 

Get full prescribing information for Genotropin at MPR

Administration

Genotropin, Norditropin, and Omnitrope  are all administered subcutaneously at a dosage of 0.24 mg/kg/week for PWS.^4-6 

Get full prescribing information for Norditropin at MPR

Adverse Effects

The drug-related side effects of somatropin in children with PWS include edema, aggressive behavior, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia.^4-6,10 

Get full prescribing information for Omnitrope at MPR

Warnings and Precautions

In children with PWS with 1 or more risk factors such as severe obesity, a history of upper airway obstruction or sleep apnea, or an unknown respiratory infection, there have been fatalities following the initiation of somatropin. Male patients may be at a higher risk than female patients if they have 1 or more of these variables.¹⁰ 

Before starting somatropin therapy, patients with PWS should be screened for symptoms of upper airway obstruction and sleep apnea. Treatment with somatropin should be stopped if patients exhibit symptoms of upper airway blockage, such as the development or worsening of snoring or new-onset sleep apnea.¹⁰

Polysomnography screening for obstructive sleep apnea should be conducted before starting treatment, 3 to 6 months into treatment, and then annually.³

All patients with PWS on somatropin should also maintain a healthy weight and be closely monitored for signs of respiratory infection. Respiratory infections should be identified quickly and promptly treated.¹⁰ 

Read more about PWS complications

Safety and Efficacy in Trials

In 2 open-label, randomized controlled clinical trials, participants were randomly assigned to receive either somatropin or no treatment for the first year, and for the second year of the studies, all participants received somatropin. Somatropin was administered as a daily subcutaneous injection. In Study 1, somatropin was administered to the treatment group at a dose of 0.24 mg/kg/week for the duration of the experiment. The control group received somatropin at a dose of 0.48 mg/kg/week during the second year. In Study 2, somatropin was administered to the treatment group at a dose of 0.36 mg/kg/week for the duration of the experiment. The control group received somatropin at a dose of 0.36 mg/kg/week during the second year.^4-6,8

Patients who were administered somatropin demonstrated significant gains in linear growth over the first year of research compared to those who were not. In the second year, when both groups were treated with somatropin, linear growth continued to rise. The patients who received somatropin also experienced changes in their body composition. Lean body mass and the ratio of lean to fat tissue both increased, and the amount of fat mass decreased. Body weight changes were similar to those observed in individuals who did not receive treatment. Compared to patients who did not receive treatment, patients administered somatropin did not experience accelerated bone age.^4-6,8 

Read more about PWS clinical trials

References

1. Strong T. Growth hormone therapy for PWS. Foundation for Prader-Willi Research. August 24, 2016. Accessed July 26, 2023.
2. Grugni G, Sartorio A, Crinò A. Growth hormone therapy for Prader-willi syndrome: challenges and solutions. Ther Clin Risk Manag. 2016;12:873-881. doi:10.2147/TCRM.S70068
3. Szabadi S, Sila Z, Dewey J, Rowland D, Penugonda M, Ergun-Longmire B. A review of Prader-Willi syndrome. Endocrines. 2022;3(2):329-348. doi:10.3390/endocrines3020027
4. NORDITROPIN® (somatropin) injection, for subcutaneous use. https://www.accessdata.fda.gov/. Updated February 2018. Accessed August 16, 2023.
5. OMNITROPE® (somatropin [rDNA origin] injection), for SUBCUTANEOUS use. https://www.accessdata.fda.gov/. Updated August 2014. Accessed August 16, 2023.
6. GENOTROPIN (somatropin) for injection, for subcutaneous use. https://www.accessdata.fda.gov/. Updated December 2016. Accessed August 16, 2023.
7. Fermin Gutierrez MA, Mendez MD. Prader-Willi syndrome. In: StatPearls [Internet]. StatPearls Publishing; 2023. Accessed July 26, 2023.
8. Genotropin (somatropin) injection. CenterWatch. Accessed July 26, 2023.
9. Somatotropin. DrugBank Online. June 13, 2005. Updated July 26, 2023. Accessed July 26, 2023.
10. Genotropin prescribing information. Drugs.com. Updated April 1, 2023. Accessed July 26, 2023.

Reviewed by Hasan Avcu, MD, on 7/30/2023.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.