Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial
Authors: Sävendahl Lars , Battelino Tadej , Brod Meryl , Højby Rasmussen Michael , Horikawa Reiko , Juul Rasmus Vestergaard , Saenger Paul ,   REAL 3 study group, Furthner Dieter , Piringer Bettina , Auer-Hackenberg Lorenz , Schmitt Klaus , Reitmayr Marlene , Bronstein Marcello Delano , Lima Francisco Samuel Magalhães , Wabitsch Martin , Posovszky Carsten , Böttcher Volker , Mann Alexander , Hershkovitz Eli , Haim Alon , Lowenthal Neta , Hamiel Orit , Levin Sharon Sheinvald , Mazor-Aronovitch Kineret , Ben-Ami Michal , Shraga Yael Levy , Modan Dalit , Gruber Noah , Phillip Moshe , Lebenthal Yael , Tenenbaum Ariel , Eliakim Alon , Dror Nitzan , Haviv Ruby , Zuckerman-Levin Nehama , Shehadeh Naim , Givon Liav , Elemy Ameer , Marji Miriam , Gepstein Vardit , Praveen V P , Aswin P , Abraham Nithiya , Khadgawat Rajesh , Gupta Yashdeep , Khadilkar Vaman , Khadilkar Anuradha , Lad Sagar , Horikawa Reiko , Naiki Yasuhiro , Ogiwara Yasuko , Chiba Yuta , Fujisawa Yusuke , Terada Yumiko , Yoshida Tomoko , Kinjo Kenichi , Tsukamura Atsushi , Ida Shinobu , Etani Yuri , Shoji Yasuko , Kawai Masanobu , Nakajima Hisakazu , Mori Jun , Fukuhara Shota , Shigehara Keiichi , Morimoto Hidechika , Tsuma Yusuke , Kawabe Yasuhiro , Ota Takeshi , Kashimada Kenichi , Nakagawa Ryuichi , Tsuji Atsumi , Nomura Risa , Takasawa Kei , Yamauchi Takeru , Ishii Kanako , Toda Naoko , Ohkubo Kazuhiro , Yorifuji Tohru , Hosokawa Yuki , Kawakita Rie , Hashimoto Yukiko , Sakakibara Azumi , Higuchi Shinji , Soneda Shun , Ogushi Kenichiro , Yatsuga Shuichi , Koga Yasutoshi , Matsumoto Takako , Kitamura Miyuki , Sävendahl Lars , Nergårdh Ricard , Battelino Tadej , Tansek Mojca Zerjav , Turan Serap , Bereket Abdullah , Atay Zeynep , Akbarzade Azad , Bolshova Olena , Tronko Mykola , Vyshnevskaya Olga , Sprynchuk Natalia , Lukashuk Iryna , Muz Natalia , Marchenko Tatyana , Chorna Nataliya , Konovalova Marіana , Zelinska Liliya , Silverman Lawrence , Cerame Barbara , Cheruvu Sunita , Chin Daisy , Ebner-Lyon Laurie , Fox Marie , Nicolette-Gentile Marianna , Sabanosh Kristin , Starkman Harold , Marshall Ian , Gangat Mariam , Balachandar Sadana , Backeljauw Philippe , Dauber Andrew , Tyzinski Leah , Saenger Paul H , Siliezar Luis Zamora , Velasco Jacqueline P , Ross Judith L , Bardsley Martha , Kowal Karen , Kletter Gad B , Frazier Britney G , Garrison Kathryn 
Published: January 2020

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 once-weekly 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).