Pediatric Endocrinology, University of Minnesota Medical School, Minneapolis, MN, USA.
Department of Neuroendocrinology and Neurology, Barrow Pituitary Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USA.
Drug Des Devel Ther. 2022 Jun 29;16:2055-2066. doi: 10.2147/DDDT.S336285. eCollection 2022.
Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration in August 2021 for the treatment of pediatric growth hormone deficiency (GHD). Lonapegsomatropin is a prodrug consisting of unmodified GH transiently conjugated to methoxypolyethylene glycol which enables time-release of GH with a half-life of ~25 hours allowing for once-weekly administration. Clinical trials of lonapegsomatropin have demonstrated positive efficacy results in children (phase 2 and 3) and adults (phase 2) with GHD. The phase 3 trial in children with GHD established non-inferiority and statistical superiority of height velocity with lonapegsomatropin (11.2 cm/yr) compared to daily GH (10.3 cm/yr), with no concerning side effects with lonapegsomatropin. Similar growth responses have been reported in other LAGH products in phase 2 (somapacitan) and phase 3 (somatrogon) trials. Lonapegsomatropin is distributed in temperature-stable, prefilled cartridges at 9 different doses that can be prescribed based upon specific weight brackets designed to deliver approximately 0.24 mg/kg/wk. An electronic delivery device is required to combine the powdered medication with the diluent and deliver the medication subcutaneously through a small gauge needle to the recipient. The pharmacodynamic data from the clinical trials of lonapegsomatropin has been used to develop models to estimate an average IGF-1 value drawn at any time during the weekly injection interval. This average IGF-1 value may be used to for safety monitoring and/or to guide dose adjustment. New LAGH products, including lonapegsomatropin, may potentially improve patient adherence, quality of life and clinical outcomes, particularly in patients with poor adherence to daily GH injections in the future. With the availability of new LAGH products, clinicians will need to identify the best candidates for LAGH therapy and understand how to monitor and adjust therapy. Long-term surveillance studies are needed to demonstrate adherence, efficacy, cost-effectiveness and safety of LAGH preparations.
Lonapegsomatropin，一种长效 GH 治疗药物（LAGH），于 2021 年 8 月获得美国食品和药物管理局批准，用于治疗儿童生长激素缺乏症（GHD）。Lonapegsomatropin 是一种前药，由未修饰的 GH 与甲氧基聚乙二醇短暂缀合而成，能够实现 GH 的时控释放，半衰期约为 25 小时，允许每周给药一次。Lonapegsomatropin 在 GHD 儿童（2 期和 3 期）和成人（2 期）的临床试验中显示出了积极的疗效结果。在 GHD 儿童的 3 期临床试验中，Lonapegsomatropin（11.2cm/yr）与每日 GH（10.3cm/yr）相比，身高速度具有非劣效性和统计学优势，Lonapegsomatropin 没有令人担忧的副作用。在其他 LAGH 产品的 2 期（somapacitan）和 3 期（soma-trogon）试验中也报告了类似的生长反应。Lonapegsomatropin 以 9 种不同剂量的稳定温度预填充 cartridges 形式给药，可根据特定体重范围进行处方，旨在每周输送约 0.24mg/kg/wk。需要使用电子输送装置将粉末状药物与稀释剂混合，并通过小口径针头将药物皮下输送给接受者。Lonapegsomatropin 的临床试验中的药效学数据已被用于开发模型，以估计在每周注射间隔内的任何时间抽取的平均 IGF-1 值。该平均 IGF-1 值可用于安全性监测和/或指导剂量调整。新的 LAGH 产品，包括 lonapegsomatropin，未来可能会提高患者的依从性、生活质量和临床结局，特别是对那些每日接受 GH 注射依从性差的患者。随着新的 LAGH 产品的出现，临床医生需要确定最适合 LAGH 治疗的患者，并了解如何监测和调整治疗。需要进行长期监测研究，以证明 LAGH 制剂的依从性、疗效、成本效益和安全性。
