Growth Hormone Somatropin is Effective, Does Not Increase Cancer or Diabetes Risk

Sandro Loche, MD

Credit: Endocrine Society

A new study found the biosimilar recombinant human growth hormone (rhGH), somatropin (Omnitrope), is effective and well-tolerated in pediatric patients.¹

“No signs of an increased diabetogenic potential, increased risk of new or recurrent malignancies, or anti-rhGH antibody-induced lack or loss of efficacy has been observed across all the indications,” wrote investigators, led by Sandro Loche, MD, from Ospedale Microitemico.

Ever since the 1950s, children with growth hormone deficiencies have had injections to assist them in growing—and the therapy was first approved in 1985. Recombinant human growth hormone replacement therapy can treat other growth disorders—small for gestational age, Turner Syndrome, children with idiopathic short stature, Prader-Willi syndrome, chronic renal insufficiency, and Noonan syndrome.

In the European Union, somatropin was approved as a biosimilar recombinant human growth hormone back in 2006 due to its comparable quality, safety, and effectiveness to the reference product, Genotropin.² However, the Patients Treated with Omnitrope (PATRO) Children study, an observational, multicenter, international, longitudinal post-marketing surveillance study aimed to monitor the long-term safety and effectiveness of this treatment in pediatric patients.¹ Monitoring long-term safety is essential to ensure the injection does not put a patient at risk of cancer, diabetes, or other harmful conditions.

The study included 7359 children with several types of growth disorders, collected from 304 sites around the world in 15 countries. Patients were either infants, children, or adolescents whose parents or caregivers provided consent. Most (86%) of the children did not receive growth hormone injections before the study, but some did and were referred to as “pretreated.”

All children in the study received daily somatropin injections. More than half of the children (57.9%) had the injection due to growth hormone deficiency, and some of the children received the injection due to being born small for their gestational age (26.6%).

On average, children were exposed to the biosimilar somatropin for 3.66 years. Mean durations varied for different growth disorders: growth hormone deficiency (3.56 years), Turner Syndrome (3.54), CRI (2.77), Small for Gestational Age (3.86), Prader-Willi Syndrome (4.97), idiopathic short stature (3.22), and other (3.66).

About half (54.1%) of the patients experienced adverse events, and most were mild or moderate in severity—with adverse events resolving completely in 80.7% of patients. Adverse events believed to be caused by treatment occurred in only 8.3% of patients, and the most common ones were headache occurring in 1.6% of patients, followed by injection-site pain (1.1%), injection-site hematoma (1.1%), and arthralgia (0.6%).

One reason patients discontinued treatment was because they reached adult height or bone age maturity (12.1%). Other reasons children discontinued the study included not following up (8.1%), site closure (8%), and reaching near-adult height (8%). Only 1.9% of patients discontinued due to adverse events.

The study found children receiving the somatropin injection had a low risk of developing diabetes and cancer, comparable to what was found in previous studies. The incidence rate of type 2 diabetes mellitus was 0.11 per 1000 person-years across all patients, and 0.13 person-years in patients born small for gestational age. The incidence rate for other harmful conditions was 0.22 per 1000 person-years.

The team noted a “sustained catch-up growth” in 6589 patients, demonstrating the effectiveness of somatropin. With 5 years of treatment, height increased from a range of +1.79 (– 3.7 to 6.2) in patients who never received growth hormone injections and +0.73 (– 1.4 to 3.7) in pretreated patients.

Furthermore, the height velocity height standard deviation score of treatment-naïve patients increased from – 3.02 (-11.9 to 12.0) at baseline to +3.85) after 1 year and +1.18 (-9.0 to 11.7) after 5 years.

“Increase in height velocity was most pronounced during the first year of treatment,” investigators wrote.

After the study, 24.7% of patients reached adult height. The mean age when patients reached adult height was 15.87 years in treatment-naïve patients and 15.98 years in pretreated patients; girls who were both treatment-naïve and pretreated were more likely to reach adult height about a year before boys.

Despite the adverse reactions, the growth hormone was considered well-tolerated and not associated with an increased risk of cancer or diabetes in children.

Yet, investigators highlighted limitations. For instance, they collected data following routine clinical practice and not strict standardized protocols which could have led to missing data, carried out assessments and laboratory tests locally and not centrally which could have led to variations between sites, and the treatment lasted approximately 3 years which may not have been enough time for malignancies to develop.

“Beyond clinical trials, biosimilar rhGH has generated more than 300 million patient-days of treatment experience across 80 approved countries worldwide (across approved rhGH indications) until January 2022,” investigators concluded. “The growing clinical experience with EMA-approved biosimilars, including biosimilar rhGH, should offer additional reassurance to healthcare professionals and patients that these agents are as effective and well tolerated as others, thus widening patients’ access to life-changing treatments worldwide.”

^References

1. ^{Loche S, Kanumakala S, Backeljauw P, et al. Safety and Effectiveness of a Biosimilar Recombinant Human Growth Hormone in Children Requiring Growth Hormone Treatment: Analysis of Final Data from PATRO Children, an International, Post-Marketing Surveillance Study. Drug Des Devel Ther. 2024;18:667-684. Published 2024 Mar 2. doi:10.2147/DDDT.S440009}
2. ^{European Medicines Agency [Internet]. Omnitrope® European public assessment report (EPAR), updated 2018; 2008. Available from: https://www.ema.europa.eu/en/documents/overview/omnitrope-epar-summary-public_en.pdf. Accessed March 18, 2024.}