Human Growth Hormone: No Longer a Daily Battle

Few individuals are born with insufficient amounts of human growth hormone, causing interference with their development and daily life. Human growth hormone is an important component in cell reproduction, body composition, muscle and bone growth, cardiovascular health, and sugar and fat metabolism. ¹ Although it is present in people of all ages, it is crucial for young children as this is when the majority of growth occurs.¹ For this reason, a human growth hormone deficiency is a serious concern amongst primarily pediatric, as well as adult populations.

“Originally the lack of growth hormone had no tangible solution; however, the deficiency is now treatable.”

Growth hormone deficiency occurs as a result of a lack of growth hormone production by the pituitary gland and has been found to more commonly affect children.¹ The annual incidence of new human growth hormone deficiency cases is 5-10 per 10,000 children. ² Originally the lack of growth hormone had no tangible solution; however, the deficiency is now treatable. The most common approach to ensuring a sufficient quantity of growth hormone is through injections with a synthetic version. Typically, those affected begin injections as soon as a failure of hormone growth hormone secretion is identified. ³ The presence of physical abnormalities in children who are not immediately treated causes self-esteem issues and can lead to other mental health concerns. Delayed treatment in children results in delayed puberty, short stature, a younger-looking appearance, and increased fat storage; however, those diagnosed early recover well.

Growth hormone deficiency is also present in adult populations, where the hormone is responsible for maintaining body structure and proper metabolism. ⁴ A deficiency typically results in reduced bone strength, a lack of stamina, depression, anxiety, a lack of concentration, and could potentially lead to diabetes and cardiovascular morbidity. ⁴ Although these symptoms seem severe, the main population at risk is children as human growth hormone is required for proper development and a lack could have extensive impacts.

“Current therapies on the market are daily injection only, which can be burdensome for both patients and caregivers: it is not uncommon for a patient to miss more than one injection per week.”

Over the course of approximately 30 years, various companies have been working on the best method to provide artificial human growth hormone for those who are deficient. In 1985, the FDA approved the first synthetic human growth hormone, somatotropin, which required a daily injection.⁵ Since this original injection method, there have been many developments. The present-day daily human growth hormones are equally safe and effective, however, their formulation, storage, and delivery methods vary resulting in differing convenience levels. Current therapies on the market are daily injection only, which can be burdensome for both patients and caregivers: it is not uncommon for a patient to miss more than one injection per week. ⁵ A lack of compliance can result in suboptimal results, suggesting that a patient would be unable to make positive progress or recover as expected. This lack of efficacy is universal among patients, caregivers, and physicians and is considered one of the greatest barriers in growth hormone deficiency management.

Growth hormone deficiency occurs In hopes of improving the consistency of the injections, and therefore the effectiveness, pharmaceutical companies have been developing easier delivery options for patients. Many companies are focusing on developing a long-acting human growth hormone, which would require less frequent administration. However, there are no long-acting approved treatments yet. There are three long-acting human growth hormones in clinical development: Novo Nordisk’s Somapacitan, Pfizer/OPKO’s Somatrogon, and Ascendis Pharma’s TransCon Growth Hormone. Novo Nordisk’s Somapacitan, for weekly administration of growth hormone, matched the therapeutic benefits of once-daily Norditropin® (somatropin) in a phase II trial in children with growth hormone deficiency. Novo Nordisk is starting Phase III studies of somapacitan in GHD children, and the results of the trial are expected in late 2020. ^6,7 Pfizer/OPKO’s somatrogon showed positive data in Phase II trial and is expected to complete a Phase III trial in prepubertal GHD patients by November 2019. ⁷ Ascendis Pharma reported comprehensive results of its Phase II trial of once-weekly TransCon Growth Hormone which demonstrated that the sustained release TransCon Growth Hormone is comparable to daily human growth hormone in terms of efficacy, safety, and tolerability in children with GHD. ⁷ Ascendis Pharma expects to complete a Phase III trial in prepubertal GHD patients by November 2018. ⁷ All the companies mentioned above are also developing an auto-injector to administer long-acting Growth Hormone in a single, low-volume injection via a small needle.

Growth hormone deficiency occurs The increase in research and development in the past 30 years for human growth hormone has been exponential and continues to be an area of expansion. Today children and adults with growth hormone deficiency require daily injections, which can be a considerable treatment burden for patients and caregivers. However, shifting to a weekly injection with a non-inferior growth response will be more convenient and has the potential to result in increased adherence and hence better treatment outcomes. Further, a weekly treatment would represent a significant development for children and their families, enabling them to live less disrupted lives. The promising developments by major pharmaceutical companies are predicted to introduce a new generation of weekly growth hormone therapy by 2020 in the world market.

“Shifting to a weekly injection with a non-inferior growth response will be more convenient and has the potential to result in increased adherence and hence better treatment outcomes.”

Works Cited:

1. Bamba V. Pediatric Growth Hormone Deficiency Guidelines. Pediatric Growth Hormone Deficiency Guidelines: Guidelines Summary. https://emedicine.medscape.com/article/923688-guidelines. Published August 27, 2018.

2. Stanley T. Diagnosis of Growth Hormone Deficiency in Childhood. Current Opinion in Endocrinology, Diabetes, and Obesity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279941/. Published February 1, 2012.

3. Growth Hormone Deficiency. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/growth-hormone-deficiency/

4. Bamba V. Pediatric Growth Hormone Deficiency: Practice Essentials, Background, Pathophysiology. Medscape. https://emedicine.medscape.com/article/923688-overview#a4. Published August 27, 2018.

5. Ayyar. S, Vageesh. History of Growth Hormone Therapy. Indian Journal of Endocrinology and Metabolism. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183530/. Published September 15, 2011.

6. House DW. Novo's once-weekly somapacitan on par with daily Norditropin in mid-stage study. Seeking Alpha. https://seekingalpha.com/news/3393649-novos-weekly-somapacitan-par-daily-norditropin-mid-stage-study. Published September 28, 2018.

7. Human Growth Hormone Deficiency (GHD) Drugs Market Clinical Analysis 2018 to 2023. Press Release - Digital Journal. http://www.digitaljournal.com/pr/3971615. Published October 10, 2018.

Cite This Article:

Pastrak M., Chan G., Palczewski K., Zhang B., Lewis K., Ho J. Human Growth Hormone: No Longer a Daily Battle. Illustrated by S. Montakhaby. Rare Disease Review. November 2019. DOI: 10.13140/RG.2.2.33119.20647.