Once-Weekly somapacitan vs daily GH in children with GH deficiency: Results from a randomized phase 2 trial

Lars Sävendahl, Tadej Battelino, Meryl Brod, Michael Højby Rasmussen, Reiko Horikawa, Rasmus Vestergaard Juul, Paul Saenger, Dieter Furthner, Bettina Piringer, Lorenz Auer-Hackenberg, Klaus Schmitt, Marlene Reitmayr, Marcello Delano Bronstein, Francisco Samuel Magalhaes Lima, Martin Wabitsch, Carsten Posovszky, Volker Bottcher, Alexander Mann, Eli Hershkovitz, Alon HaimNeta Lowenthal, Orit Hamiel, Sharon Sheinvald Levin, Kineret Mazor-Aronovitch, Michal Ben-Ami, Yael Levy Shraga, Dalit Modan, Noah Gruber, Moshe Phillip, Yael Lebenthal, Ariel Tenenbaum, Alon Eliakim, Nitzan Dror, Ruby Haviv, Nehama Zuckerman-Levin, Naim Shehadeh, Liav Givon, Ameer Elemy, Miriam Marji, Vardit Gepstein, V. P. Praveen, P. Aswin, Nithiya Abraham, Rajesh Khadgawat, Yashdeep Gupta, Vaman Khadilkar, Anuradha Khadilkar, Sagar Lad, Yasuhiro Naiki, Yasuko Ogiwara, Yuta Chiba, Yusuke Fujisawa, Yumiko Terada, Tomoko Yoshida, Kenichi Kinjo, Atsushi Tsukamura, Shinobu Ida, Yuri Etani, Yasuko Shoji, Masanobu Kawai, Hisakazu Nakajima, Jun Mori, Shota Fukuhara, Keiichi Shigehara, Hidechika Morimoto, Yusuke Tsuma, Yasuhiro Kawabe, Takeshi Ota, Kenichi Kashimada, Ryuichi Nakagawa, Atsumi Tsuji, Risa Nomura, Kei Takasawa, Takeru Yamauchi, Kanako Ishii, Naoko Toda, Kazuhiro Ohkubo, Tohru Yorifuji, Yuki Hosokawa, Rie Kawakita, Yukiko Hashimoto, Azumi Sakakibara, Shinji Higuchi, Shun Soneda, Kenichiro Ogushi, Shuichi Yatsuga, Yasutoshi Koga, Takako Matsumoto, Miyuki Kitamura, Ricard Nergardh, Mojca Zerjav Tansek, Serap Turan, Abdullah Bereket, Zeynep Atay, Azad Akbarzade, Olena Bolshova, Mykola Tronko, Olga Vyshnevskaya, Natalia Sprynchuk, Iryna Lukashuk, Natalia Muz, Tatyana Marchenko, Nataliya Chorna, Mariana Konovalova, Liliya Zelinska, Lawrence Silverman, Barbara Cerame, Sunita Cheruvu, Daisy Chin, Laurie Ebner-Lyon, Marie Fox, Marianna Nicolette-Gentile, Kristin Sabanosh, Harold Starkman, Ian Marshall, Mariam Gangat, Sadana Balachandar, Philippe Backeljauw, Andrew Dauber, Leah Tyzinski, Luis Zamora Siliezar, Jacqueline P. Velasco, Judith L. Ross, Martha Bardsley, Karen Kowal, Gad B. Kletter, Britney G. Frazier, Kathryn Garrison

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Context: Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective: The objective of this study is to evaluate the efficacy, safety, and tolerability of onceweekly somapacitan vs once-daily GH. Design: REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting: This study took place at 29 sites in 11 countries. Patients: Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions: Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures: The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results: At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week-daily GH): 1.7 [95% CI -0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was -1.62 (0.86), -1.09 (0.78), and 0.31 (1.06), respectively, vs -0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions: In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

Original languageEnglish
Pages (from-to)E1847-E1861
JournalJournal of Clinical Endocrinology and Metabolism
Volume105
Issue number4
DOIs
StatePublished - 1 Apr 2020

Keywords

  • Growth hormone
  • Growth hormone deficiency
  • Growth hormone replacement therapy
  • Long-acting growth hormone
  • Somapacitan
  • Treatment burden

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