Weekly TransCon Hormone Injections Could Replace Daily Therapy

Aristides K. Maniatis, MD

A weekly growth hormone injection could replace daily injections in children with growth hormone deficiencies.

A team, led by Aristides K. Maniatis, MD, Rocky Mountain Pediatric Endocrinology, evaluated children with growth hormone deficiency of a broad range of baseline demographics and treatment durations, who switched from daily injection therapies to once-weekly TransCon human growth hormone (hGH).

Maniatis explained in a presentation for the ENDO Online 2020 virtual conference that poor adherence is a major issue with the daily growth hormone regimen, with two-thirds of patients missing at least 1 injection per week.

TransCon hGH is an investigational long-acting prodrug consisting of hGH, an inert carrier that protects it, and a linker that temporarily binds the other 2 components. The unmodified treatment is gradually released in a predictable manner when inject into the body and physiologic pH and temperature.

In the study, all subjects initiated open-label once-weekly TransCon hGH 0.24 mg hGH/kg/week regardless of prior daily dosages. The 164 participants in the trial were between 3-17 years old who were previously either treatment-naïve or treated with daily hGH for ≤130 weeks. The mean age at baseline was 10.6 years old, with 97.9% of the participants coming off of a prior daily regimen of 0.29 mg/kg/week, with only 3 participants going in treatment naïve.

More than half of the subjects (56.8%) experienced a treatment-emergent adverse event, but only 4.1% experiencing an adverse event related to the study drug.

The investigators sought primary objectives of assessing the safety and tolerability over the course of 26 weeks. They included efficacy measures of annualized height velocity (AHV), height standard deviation scores (SDS), and insulin-like growth factor 1 (IGF-1) SDS.

The mean hemoglobin a1c remained 5.2% at baseline and week 26, while no neutralizing antibodies were detected.

Low-titer anti-hGH binding antibodies were found in 2.8% of the subjects. The growth outcomes were found as expected for the treatment-experienced heterogenous population, with a least-squares mean LSM) AHV of 8.7 cm/year (95% CI: 8.2, 9.2) at week 26 and LSM height SDS change from baseline to Week 26 of +0.25 (95% CI: 0.21, 0.29).

In the age-defined subgroups, the mean observed AHV at the conclusion of the trial ranged from 8.2-16.2 cm/year, while the mean observed height SDS change from baseline to week 26 ranged from +0.23 to +0.96.

The investigators also discovered the linear relationship between average IGF-1 SDS and TransCon hGH doses in previous treatment-naïve trials was preserved in the sample of treatment-experienced children who had dose titrations.

The investigators sought primary objectives of assessing the safety and tolerability over the course of 26 weeks. They included efficacy measures of annualized height velocity (AHV), height standard deviation scores (SDS), and insulin-like growth factor 1 (IGF-1) SDS.

“TransCon hGH treatment outcomes, including AHV and height SDS, were as expected across a diversity of ages, disease characteristics, and treatment experiences, reflective of a real-world setting,” the authors wrote. “Dose titrations of TransCon hGH demonstrated a predictable IGF-1 response. Switching to TransCon hGH resulted in a similar adverse event profile to daily hGH therapy.”

The investigators administered a questionnaire to the patients in the trial and found 83% of children and 88% of parents preferred the new treatment because of decreased frequency of injections.

The study, “OR10-05 Phase 3 FliGHt Trial: Experience of Switching from Daily Growth Hormone Therapy to Once-Weekly TransCon HGH in Children with Growth Hormone Deficiency,” was published online in the Journal of the Endocrine Society.