Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial

• Published in: The journal of clinical endocrinology and metabolism 2020-04, Vol.105 (4), p.e1358-e1376
• Main Authors: Johannsson, Gudmundur, Gordon, Murray B, Højby Rasmussen, Michael, Håkonsson, Ida Holme, Karges, Wolfram, Sværke, Claus, Tahara, Shigeyuki, Takano, Koji, Biller, Beverly M K
• Format: Article
• Language: English
• Subjects: adult growth hormone deficiency; Biomarkers - analysis; Body Composition; Body mass; Dose-Response Relationship, Drug; Double-Blind Method; Dual energy X-ray absorptiometry; Dwarfism, Pituitary - drug therapy; Dwarfism, Pituitary - pathology; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Follow-Up Studies; Growth hormones; Hormone Replacement Therapy; Human Growth Hormone - therapeutic use; Humans; hypopituitarism; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - analysis; Insulin-like growth factors; Lean body mass; long-acting growth hormone; Male; Middle Aged; Online Only; Prognosis; REAL 1; Recombinant Proteins - therapeutic use; Safety; somapacitan
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa049

Abstract 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).