Endocrine Abstracts

Background: Following the 34-week, double-blind, placebo-controlled main phase of REAL-1 (NCT02229851), this open-label trial extension evaluated efficacy and safety of somapacitan in patients aged 23–79 years with AGHD, for an additional 52 weeks (8 weeks’ dose titration followed by 44 weeks’ fixed dose treatment; 86 weeks’ treatment in total).

Methods: Patients completing the main trial entered the extension: 1) somapacitan-treated patients continued on that treatment; 2) daily growth hormone (GH)-treated patients were re-randomised 1:1 to somapacitan or daily GH; 3) patients receiving placebo were switched to somapacitan. Starting doses were age- and gender-dependent and titrated towards a target insulin-like growth factor-I standard deviation score (IGF-I SDS) −0.5 to +1.75. Changes from the original baseline to end of extension period in body composition were evaluated by dual-energy X-ray absorptiometry (truncal fat %, truncal fat mass, visceral adipose tissue %, visceral adipose tissue, total fat mass, android fat mass, gynoid fat mass, truncal lean body mass, appendicular skeletal muscle mass, and lean body mass). IGF-I SDS and lipid profiles were also compared. Exploratory analyses on changes from baseline were based on mixed models of repeated measures, comparing somapacitan/somapacitan and daily GH/daily GH arms. 300 patients were treated in the main phase and 272 (91%) in the extension.

Results: Mean patient age was 45.1 years; 51.7% were female. Mean exposure (during the extension alone) was 355 (somapacitan/somapacitan) and 349 days (daily GH/daily GH), respectively. After 86 weeks’ treatment, target IGF-I SDS were achieved in all treatment arms (mean values [SD], somapacitan/somapacitan: from −2.54 [1.26] to −0.22 [1.27]; placebo/somapacitan: −2.64 [1.28] to −0.31 [1.08]; daily GH/daily GH: −2.33 [1.28] to −0.24 [1.32]; daily GH/somapacitan: −2.75 [1.20] to −0.39 [1.12]). The beneficial effects of somapacitan on body composition observed in the main phase were maintained and did not differ statistically significantly between the somapacitan/somapacitan and daily GH/daily GH arms (P>0.05). There were no statistically significant differences in IGF-I SDS or lipid parameters between the somapacitan/somapacitan and daily GH/daily GH arms. Incidence, severity and type of adverse events were similar for somapacitan and daily GH treatment. Few injection site reactions were reported and all were mild to moderate in severity. No anti-somapacitan antibodies were detected.

Conclusions: Body composition changes and IGF-I SDS observed in the main phase of REAL-1 were maintained in the trial extension. No new safety signals/tolerability issues were identified for somapacitan.