2. Academic Validation
  3. Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial

Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial

  • J Clin Endocrinol Metab. 2022 Nov 25;107(12):3378-3388. doi: 10.1210/clinem/dgac513.
Bradley S Miller 1,  Joanne C Blair 2,  Michael Højby Rasmussen 3,  Aristides Maniatis 4,  Rasmus Juul Kildemoes 3,  Jun Mori 5,  Michel Polak 6,  Rikke Beck Bang 7,  Volker Böttcher 8,  Stefano Stagi 9,  Reiko Horikawa 10
Affiliations

Affiliations

  • 1 Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
  • 2 Department of Endocrinology, Alder Hey Children's NHS Foundation Trust, Liverpool, L14 5AB, UK.
  • 3 Novo Nordisk A/S, Søborg, 2860, Denmark.
  • 4 Rocky Mountain Pediatric Endocrinology, Centennial, 80112 CO, USA.
  • 5 Division of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka 534-0021, Japan.
  • 6 Service d'Endocrinologie, Gynécologie et Diabétologie Pédiatriques, Hôpital Universitaire Necker Enfants Malades Paris, Assistance Publique-Hôpitaux de Paris, Paris 75015, France.
  • 7 Novo Nordisk A/S, Aalborg 9220, Denmark.
  • 8 Division of Pediatric Endocrinology and Metabolism, MVZ Endokrinologikum Frankfurt am Main, Frankfurt 60596, Germany.
  • 9 Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence 50139, Italy.
  • 10 Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo 157-0074, Japan.
PMID: 36062966 DOI: 10.1210/clinem/dgac513
Abstract

Context: Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in children with GH deficiency (GHD).

Objective: To demonstrate efficacy and safety of somapacitan vs daily GH.

Methods: REAL4 is a randomised, multinational, open-labeled, active-controlled parallel group phase 3 trial, comprising a 52-week main trial and 3-year extension (NCT03811535).

Setting: Eighty-six sites across 20 countries.

Patients: 200 treatment-naïve patients were randomized and exposed.

Interventions: Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (Norditropin; 0.034 mg/kg/d), administered subcutaneously.

Main outcome measures: The primary endpoint was annualized height velocity (HV; cm/y) at week 52. Additional assessments included HV SD score (SDS), height SDS, bone age, IGF-I SDS, patient-reported outcomes, and safety measures.

Results: Estimated mean HV at week 52 was 11.2 and 11.7 cm/y for somapacitan and daily GH, respectively. Noninferiority was confirmed. Changes in HV SDS, height SDS, bone age, and IGF-I SDS from baseline to week 52 were similar between treatment groups. At week 52, mean IGF-I SDS values were similar between treatment groups and within normal range (-2 to +2). Safety of somapacitan was consistent with the well-known daily GH profile. Low proportions of injection-site reactions were reported for somapacitan (5.3%) and daily GH (5.9%). Both treatments similarly reduced disease burden from baseline to week 52, whereas a greater treatment burden reduction was observed for somapacitan.

Conclusions: Similar efficacy for somapacitan compared to daily GH was demonstrated over 52 weeks of treatment with comparable safety and mean IGF-I SDS levels in treatment-naïve children with GHD.

Keywords

growth hormone; growth hormone deficiency; growth hormone replacement therapy; long-acting growth hormone; somapacitan; treatment burden.

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