Somatrogon injection for the treatment of pediatric growth hormone deficiency with comparison to other LAGH products

ABSTRACT

Introduction

Somatrogon (NGENLA™) is a long-acting GH (LAGH) formulation that was approved in Canada in October 2021 for the treatment of pediatric growth hormone deficiency (GHD). Somatrogon has also received approval in Australia, Japan, the European Union, the USA, and the UK. Somatrogon is a glycoprotein that utilizes three copies of the C-terminal peptide of human chorionic gonadotropin to delay its clearance allowing for once-weekly administration.

Areas covered

The purpose of this article is to describe the development of somatrogon for treatment of individuals with GHD. Trials of somatrogon demonstrated positive efficacy results in adults (Phase 2) and children (Phase 2 and 3) with GHD including non-inferiority of height velocity compared to daily GH, with no concerning side effects. Growth responses, pharmacodynamics and safety data are compared to other LAGH products, lonapegsomatropin and somapacitan, in Phase 3 trials in pediatric GHD.

Expert opinion

New LAGH products, including somatrogon, have the potential to increase patient adherence as well as improve quality of life and clinical outcomes. Clinicians will need to identify the best candidates for LAGH therapy and understand how to safely monitor and adjust therapy. Long-term surveillance studies are necessary to demonstrate adherence, efficacy, cost-effectiveness, and safety of LAGH preparations.

KEYWORDS:

• Growth
• long-acting growth hormone
• IGF-I
• growth hormone deficiency
• pediatric
• somatrogon

Article highlights

• Somatrogon is a LAGH developed through modification of the GH molecule to allow once weekly administration.

• The Phase 3 trial of somatrogon in children with GHD established non-inferiority of height velocity with 0.66 mg/kg/week somatrogon (10.10 cm/yr) compared to daily somatropin (9.78 cm/yr), similar to the relative responses in other once weekly LAGH products.

• In clinical trials of somatrogon and other once-weekly LAGH products in children with GHD, no concerning or new side effects have occurred.

• Antidrug antibodies were more commonly seen in the Phase III studies of somatrogon than lonapegsomatropin and somapacitan. Neutralizing antibodies against somatrogon were identified in a small number of children but had no impact on growth.

• Three new LAGH products, including somatrogon, have recently been approved for treatment of children with GHD. Real world evidence is needed to demonstrate the efficacy, cost-effectiveness, safety and improved adherence of LAGH preparations.

Declaration of interest

BS Miller is a consultant for Abbvie, Ascendis Pharma, BioMarin, Bristol Myers Squibb, EMD Serono, Endo Pharmaceuticals, Novo Nordisk, Orchard Therapeutics, Pfizer, Provention Bio and Tolmar and has received research support from Alexion, Abbvie, Aeterna Zentaris, Amicus, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health, Pfizer, Prevail Therapeutics and Sangamo Therapeutics.

KCJY has received research grants to Barrow Neurological Institute from Crinetics, Ascendis, Corcept, and Amryt; served as an occasional advisory board member for Novo Nordisk, Ascendis, Corcept, Ipsen, Amryt, Strongbridge, Crinetics, Recordati and Xeris; and served as occasional speaker for Recordati and Novo Nordisk.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this paper is an investigator for clinical trials sponsored by Ascendis and OPKO and has received research support from OPKO, Sandoz, and Pfizer.

Additional information

Funding

This paper was not funded.