TY - JOUR
T1 - Once-Weekly somapacitan vs daily GH in children with GH deficiency
T2 - Results from a randomized phase 2 trial
AU - Rasmus Vestergaard Juul
AU - REAL 3 study group
AU - Sävendahl, Lars
AU - Battelino, Tadej
AU - Brod, Meryl
AU - Rasmussen, Michael Højby
AU - Horikawa, Reiko
AU - Juul, Rasmus Vestergaard
AU - Saenger, Paul
AU - Furthner, Dieter
AU - Piringer, Bettina
AU - Auer-Hackenberg, Lorenz
AU - Schmitt, Klaus
AU - Reitmayr, Marlene
AU - Bronstein, Marcello Delano
AU - Lima, Francisco Samuel Magalhaes
AU - Wabitsch, Martin
AU - Posovszky, Carsten
AU - Bottcher, Volker
AU - Mann, Alexander
AU - Hershkovitz, Eli
AU - Haim, Alon
AU - Lowenthal, Neta
AU - Hamiel, Orit
AU - Levin, Sharon Sheinvald
AU - Mazor-Aronovitch, Kineret
AU - Ben-Ami, Michal
AU - Shraga, Yael Levy
AU - Modan, Dalit
AU - Gruber, Noah
AU - Phillip, Moshe
AU - Lebenthal, Yael
AU - Tenenbaum, Ariel
AU - Eliakim, Alon
AU - Dror, Nitzan
AU - Haviv, Ruby
AU - Zuckerman-Levin, Nehama
AU - Shehadeh, Naim
AU - Givon, Liav
AU - Elemy, Ameer
AU - Marji, Miriam
AU - Gepstein, Vardit
AU - Praveen, V. P.
AU - Aswin, P.
AU - Abraham, Nithiya
AU - Khadgawat, Rajesh
AU - Gupta, Yashdeep
AU - Khadilkar, Vaman
AU - Khadilkar, Anuradha
AU - Lad, Sagar
AU - Naiki, Yasuhiro
AU - Ogiwara, Yasuko
N1 - Publisher Copyright:
© Endocrine Society 2020.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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).
AB - 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).
KW - Growth hormone
KW - Growth hormone deficiency
KW - Growth hormone replacement therapy
KW - Long-acting growth hormone
KW - Somapacitan
KW - Treatment burden
UR - http://www.scopus.com/inward/record.url?scp=85081945845&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgz310
DO - 10.1210/clinem/dgz310
M3 - Article
AN - SCOPUS:85081945845
SN - 0021-972X
VL - 105
SP - E1847-E1861
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -
