Context Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD). Objective To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD. Design Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851). Setting Clinics in 17 countries. Patients Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial. Interventions Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH. Main outcome measures Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate. Results At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: −1.53% [−2.68; −0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH. Conclusions In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).
ObjectiveSomapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed.Design26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939).MethodsMale or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9).ResultsMean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171).ConclusionsIn this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.
The 34-week double-blind placebo-controlled main phase of REAL 1 (NCT02229851) has been previously presented (Johannsson G et al . 2018.). Now we report the open-label extension of this trial evaluating efficacy and safety of somapacitan in male/female patients aged 23-79 years with AGHD, for an additional 52 weeks (8 weeks’ dose titration followed by 44 weeks’ fixed-dose treatment) comprising a total of 86 weeks of treatment. Patients who completed the main trial entered the extension: 1) somapacitan-treated patients continued on that treatment; 2) daily GH-treated patients were re-randomized 1:1 to somapacitan or daily GH; 3) patients receiving placebo were switched to somapacitan. Starting doses were age- and gender-dependent and were titrated toward a target IGF-I SDS -0.5 to +1.75. Changes from the original baseline (BL) to end of extension period in body composition were evaluated by DXA (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 profile were also compared. Exploratory analysis on changes from BL were based on MMRM analysis models comparing somapacitan/somapacitan and daily GH/daily GH arms. 300 patients were treated in the main phase, and 272 (91%) in the extension. Mean age was 45.1 years; 51.7% were female. Mean exposure (during extension alone) was 355 (somapacitan/somapacitan) and 349 days (daily GH/daily GH). After 86 weeks of treatment, target IGF-I SDS was achieved in all treatment arms (mean values [SD], somapacitan/somapacitan: from -2.54 [1.26] to -0.22 [1.27]; placebo/somapacitan: from -2.64 [1.28] to -0.31 [1.08]; daily GH/daily GH: from -2.33 [1.28] to -0.24 [1.32]; daily GH/somapacitan: from -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 throughout the trial. Few injection-site reactions were reported and all were mild to moderate in severity. No anti-somapacitan antibodies were detected. In conclusion, the body composition changes and IGF-I SDS level observed in the main phase of REAL 1 were maintained in the trial extension. No new safety signals or tolerability issues were identified for somapacitan. Reference: Johannsson G et al. Endocr Rev. 2018;39(2 Suppl):SUN-632C-LB Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the sessio...
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