Sahlgrenska University Hospital, Göteborg, Sweden.
Allegheny General Hospital, Pittsburgh, PA.
J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1358-76. doi: 10.1210/clinem/dgaa049.
Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD).
To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD.
Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851).
Clinics in 17 countries.
Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial.
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.
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.
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.
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).
生长激素（GH）替代疗法需要每日注射 GH，这给一些患有生长激素缺乏症（AGHD）的成年患者带来了负担。
证明每周一次可逆白蛋白结合型 GH 衍生物 somapacitan 与安慰剂相比在 AGHD 中的疗效和安全性。
随机、平行组、安慰剂对照（双盲）和活性对照（开放标签）的 3 期试验，REAL 1（NCT02229851）。
17 个国家的诊所。
治疗初治的 AGHD 患者（主要研究期 301 例，扩展期 272 例）；257 例患者完成了试验。
患者随机分为 2:2:1 组，分别接受每周一次的 somapacitan、每日 GH 或每周一次的安慰剂治疗 34 周（主要期）。在 52 周的扩展期内，患者继续接受 somapacitan 或每日 GH 治疗。
使用双能 X 射线吸收法（DXA）测量身体成分。主要终点是第 34 周时躯干脂肪百分比的变化。使用胰岛素样生长因子 1（IGF-1）标准差评分（SDS）值进行剂量滴定。
在 34 周时，somapacitan 显著降低了躯干脂肪百分比（估计差值：-1.53%[-2.68；-0.38]；P = 0.0090），与安慰剂相比具有优越性，并且改善了其他身体成分参数（包括内脏脂肪和瘦体重）和 IGF-1 SDS。在 86 周时，somapacitan 和每日 GH 治疗均能维持改善效果。somapacitan 耐受性良好，与每日 GH 相比，不良反应（包括注射部位反应）相似。
在 AGHD 患者中，每周一次给予 somapacitan 优于安慰剂，somapacitan 的总体治疗效果和安全性与 GH 替代治疗长达 86 周的已知效果和安全性一致。somapacitan 可能为 AGHD 患者提供一种有效的替代每日 GH 的治疗方法。我们的工作有一个简短的可视化总结（1）。
