medwireNews: Two-year findings from the REAL4 trial support a switch from daily growth hormone (GH) to a weekly dose of the long-acting derivative somapacitan for prepubertal children with GH deficiency.
The phase 3 study investigators say the first results of the 3-year safety extension period continue to show the “noninferiority and comparable safety” of somapacitan that was previously reported for the main 52 weeks of the trial, and that the majority of patients and caregivers preferred the weekly regimen over daily treatment.
The open-label trial included 200 treatment-naïve patients, aged an average of 6.4 years (48.5% aged <6 years), and 88.0% had idiopathic GH deficiency. The children attended one of 85 centres in 20 countries and the majority were White (57.0%) or Asian (37.0%).
The participants were randomly assigned to receive weekly somapacitan 0.16 mg/kg for 2 years or to receive daily GH 0.034 mg/kg for 1 year, followed by a switch to somapacitan for year 2 of the study.
The primary endpoint of annualised average height velocity between weeks 52 and 104 was 8.4 cm/year for children who received continuous somapacitan and 8.7 cm/year for those who switched from daily to weekly therapy.
“Secondary height-related endpoints also supported sustained growth”, say Bradley Miller (University of Minnesota Medical School, Minneapolis, USA) and co-authors in The Journal of Clinical Endocrinology & Metabolism.
Specifically, the change in height velocity standard deviation score (SDS) from baseline to week 104 was a comparable 1.8 cm/year with somapacitan alone and 2.0 cm/year in the switch group, and the corresponding changes in height velocity SDS were 5.2 and 5.6 cm/year.
The change in insulin-like growth factor (IGF)-1 SDS from baseline to week 104 was 1.8 with somapacitan only and 2.1 with the switch regimen. Pharmacokinetic and pharmacodynamic modelling for weekly average IGF-1 SDS in year 2 of treatment gave values of +0.72 and +0.75, respectively, which were within normal range, the researchers say.
And the change in bone age versus chronological age over this period was 2.5 in both treatment arms.
The investigators report that somapacitan was “well tolerated”. During year 2 of treatment 2.3% of children in the somapacitan-only arm experienced injection site reactions, as did 2.9% of those in the switch group, and there were no reports of injection site pain. Nor were there “clinically relevant findings” for plasma measurements of glucose metabolism, hormones, fasting lipids or neutralising antidrug antibodies, they write.
In addition, the results of a GH patient preference questionnaire completed by the parents or caregivers of the child 4 weeks after switching from daily to weekly GH therapy showed that 90% preferred somapacitan, with a “strong” or “very strong” preference in 84.5% of cases.
Reasons for preferring somapacitan included that fewer injections were needed and there was less worry about remembering to give injections, children were not as worried, annoyed or, in as much pain from injections, and less planning was required around treatment. Indeed, 77.8% of caregivers said they would be more adherent to weekly than daily treatment.
Miller and co-workers describe the 2-year outcomes as “encouraging” but admit that “long-term surveillance studies in a real-world setting are required to best demonstrate improved adherence and clinical outcomes.”
By Lynda Williams
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