Efficacy shown for long-acting TransCon GH in prepubertal GHD children

2019-10-02T13:09:09+00:00October 2nd, 2019|News, News report, Paediatric endocrinology|

medwireNews: Children with growth hormone deficiency (GHD) receiving once-weekly TransCon human growth hormone (hGH) achieve a significantly greater annualised height velocity (AHV) than those receiving daily somatropin, results from the heiGHt trial show.

Presenting the findings at the 58th Annual ESPE Meeting in Vienna, Austria, Elpis Vlachopapadopoulou (Aglaia Kyriakou Children’s Hospital, Athens, Greece) said the data “suggest that TransCon hGH may offer a convenient alternative, once-weekly hGH therapy for children with GHD, while maintaining a similar safety profile to daily hGH.”

Vlachopapadopoulou explained that TransCon hGH is a prodrug that releases unmodified hGH in a manner that is designed to mimic daily hGH tissue distribution, physiological levels and therapeutic effects.

The drug consists of hGH (somatropin) that is transiently bound to a carrier via a TransCon linker. The linker is cleaved and releases the hGH over 1 week when at physiological pH and temperature.

In the heiGHt trial, 161 treatment-naïve prepubertal children with GHD, who had a height standard deviation score (SDS) at or below –2.0, an insulin-like growth factor (IGF)-1 SDS at or below –1.0, and a bone age at least 6 months behind chronological age were randomly assigned to receive once-weekly TransCon hGH 0.24 mg hGH/kg per week (n=105) or dose-equivalent once-daily somatropin (34 µg/kg per day; n=56).

Vlachopapadopoulou reported that not only did TransCon hGH meet the primary study endpoint of noninferiority relative to somatropin for AHV, but it was also statistically superior to the daily treatment.

Specifically, children receiving TransCon hGH had an AHV of 11.2 cm/year after 52 weeks of treatment, compared with a significantly lower 10.3 cm/year among the children who received somatropin.

Furthermore, the findings were consistent across subgroups categorised by age, sex, baseline GH-stimulation level and GHD aetiology.

Vlachopapadopoulou also reported that the incidence of poor response (AHV <8.0 cm/year) was approximately three times lower with TransCon hGH than with somatropin, at 3.8% versus 10.9%.

In addition, she showed average IGF-1 SDS was generally within the normal range following treatment for each group and that the treatment difference between the two groups in AHV was reflected in the between-group difference in IGF-1.

This parallel relationship suggests that the weekly treatment has “the same mode of action as daily hGH” and preserves the “balance between the direct and indirect effects of daily hGH”, Vlachopapadopoulou remarked.

Other outcomes measured during the heiGHt trial included bone age advancement and the bone age/chronological age ratio, which improved to a similar degree with both treatments, while cortisol, mean fasting glucose, mean glycated haemoglobin and free thyroxine levels remained stable and within the normal range throughout the 52 weeks.

Vlachopapadopoulou noted that the adverse event profile with TransCon hGH was similar to that observed with daily somatropin. There were no serious treatment-related adverse events in either group and no neutralising antibodies were detected.

She concluded that the findings of the heiGHt trial “support an integrated effect of unmodified hGH on overall endocrine health”, adding that the patients are now enrolled in the enliGHten extension study to determine the longer-term efficacy of TransCon hGH.

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

ESPE 2019; Vienna, Austria: 19–21 September