Perspectives on long-acting growth hormone therapy in children and adults.

Rayhan A Lal,Andrew R Hoffman

doi:10.20945/2359-3997000000190

Abstract

Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.

Highlights

The era of growth hormone replacement began in 1958 when Raben used human growth hormone purified from pituitary glands that had been obtained at autopsy [1]
Its use was not limited to severe growth hormone deficiency, and the drug was approved for milder forms of growth hormone deficiency, Turner syndrome, children born short for gestational age, and other causes of short stature including idiopathic short stature
While we know that long-term recombinant human growth hormone therapy is very safe [43], it is not known whether the various long-acting preparations will be safe

Summary

INTRODUCTION

The era of growth hormone replacement began in 1958 when Raben used human growth hormone purified from pituitary glands that had been obtained at autopsy [1]. In a phase 1 trial, 12 children with growth hormone deficiency received daily growth hormone 0.0286 mg/kg for 7 days, followed by 4 weeks washout and weekly Jintrolong 0.2 mg/kg for 6 weeks. A phase 3, 26-week randomized, controlled trial performed in 6 countries recruited 92 adults with growth hormone deficiency They were treated with weekly Somapacitan or daily Norditropin administered subcutaneously by pen. The Phase 2 study of weekly MOD-4023 in 54 adults with growth hormone deficiency revealed safety and comparable serum IGF-1 values to daily growth hormone [37]. Somavaratan developed by Versartis (Menlo Park, USA) was a growth hormone molecule fused with hydrophilic strings of amino acids that prolonged serum half-life It was discontinued when a phase 3 study revealed it to be inferior to daily recombinant human growth hormone [41]

CONCLUSIONS

Findings

Design