Poster Presentation ESA-SRB-APEG-NZSE 2022

Once-weekly somapacitan versus daily growth hormone (GH) in children with GH deficiency (GHD): the randomised phase 3 REAL 4 trial (#476)

Bradley S Miller 1 , Joanne C Blair 2 , Michael Højby Rasmussen 3 , Volker Böttcher 4 , Rasmus Juul Kildemoes 5 , Aristides Maniatis 6 , Rikke Beck Bang 7 , Jun Mori 8 , Michel Polak 9 10 11 12 , Stefano Stagi 13 , Reiko Horikawa 14 , Ana Svensson 15
  1. Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis , Minnesota, USA
  2. Department of Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
  3. Clinical Drug Development, Novo Nordisk A/S, Søborg, Denmark
  4. Endocrinology Clinic, Frankfurt am Main, Germany
  5. Clinical Pharmacology Rare Disease and Advanced Therapies, Novo Nordisk A/S, Søborg, Denmark
  6. Rocky Mountain Pediatric Endocrinology, Centennial, Colorado, USA
  7. Novo Nordisk A/S, Aalborg, Denmark
  8. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  9. Service d’Endocrinologie, Gynécologie et Diabétologie Pédiatriques, Hôpital Universitaire Necker Enfants Malades Paris, Assistance Publique-Hôpitaux de Paris, Paris, France
  10. Université de Paris Cité, Paris, France
  11. INSERM U1016, Institut Cochin, Paris, France
  12. Institut Imagine, Paris, France
  13. Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence, Italy
  14. National Center for Child Health and Development, Tokyo, Japan
  15. Novo Nordisk Oceania, North Sydney, NSW, Australia

Aims: GH replacement therapy usually requires daily subcutaneous injections potentially burdensome for patients and caregivers. Long-acting GH formulations aspire to a less burdensome dosing regimen as safe and efficacious as daily GH, potentially improving adherence and clinical outcomes. Somapacitan, a long-acting reversible albumin-binding GH derivative, is in development for once-weekly subcutaneous administration in children with GHD.

Methods: REAL 4, a randomised, open-labelled, active-controlled, parallel-group phase 3 trial (NCT03811535), investigated efficacy and safety of once-weekly somapacitan versus daily GH (Norditropin®), with a 52-week main phase and 3-year safety extension. Two-hundred GH-treatment-naïve, prepubertal children with GHD (74.5% male) were randomly assigned 2:1 to receive 0.16 mg/kg/week somapacitan (n=132) or 0.034 mg/kg/day daily GH (n=68) for 52 weeks. Here, we present secondary endpoints, including change from baseline to week 52 in height velocity (HV) standard deviation score (SDS), height SDS (HSDS), bone age, and patient-reported outcomes assessing disease and treatment burden.

Results: Non-inferiority in HV at week 52 was confirmed. Estimated changes in HVSDS and HSDS from baseline to week 52 were not statistically different between once-weekly somapacitan (8.05 and 1.25, respectively) and daily GH (8.82 and 1.30, respectively). Mean estimated bone age to chronological age ratio advanced similarly in both groups (somapacitan: 0.06; daily GH: 0.08), with no changes in skeletal proportions. Disease burden was reduced similarly between treatment groups from baseline to week 52. Treatment burden assessments favoured somapacitan over daily GH across all domains. The somapacitan and Norditropin® FlexPro® devices were both considered to be easy or very easy to use (96%) and to learn to use (>90%). Safety was consistent with the daily GH profile.

Conclusion: The efficacy and safety profile of somapacitan was similar to that of daily GH. Both treatments reduced disease burden to a similar degree; treatment burden was consistently lower with somapacitan.