Skip to main content
SpringerLink
Log in

Efficacy and safety of a new ready-to-use recombinant human growth hormone solution

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency (GHD) that were paramount to the development of a new recombinant human GH (rhGH, somatropin), approved as the first ‘biosimilar’ in Europe. Study 1 consisted of 3 parts performed in 89 children. The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [Somatropin Powder (Sandoz)] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [Somatropin Solution (Sandoz)] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution. Study 2 was performed in 51 children and designed to demonstrate efficacy and safety of Somatropin Powder and to confirm its low immunogenic potential; rhGH was given sc at a daily dose of 0.03 mg/kg. Primary [body height, height SD score (HSDS), height velocity, and height velocity (HV) SD score (HVSDS)] and secondary [IGF-I and IGF binding protein 3 (IGFBP-3)] efficacy end-points and safety parameters were assessed regularly. In study 1, all treatments showed comparable increases in growth. The baseline-adjusted difference between Somatropin Powder and the reference rhGH product in mean HV was −0.20 cm/yr (95% confidence interval (CI) [−1.34;0.94]) and in mean HVSDS was 0.76 (95% CI [−0.57;2.10]) after 9 months. These very small differences demonstrate comparable therapeutic efficacy between the two treatments. The results of study 2 were consistent with those seen in study 1. Equivalent therapeutic efficacy and clinical comparability in terms of safety and immunogenicity between Somatropin Powder and the reference rhGH product and between Somatropin Powder and Somatropin Solution was demonstrated. The safety and immunogenicity profiles were similar and as expected from experience with rhGH preparations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wilton P, Widlund L, Guilbaud O. Bioequivalence of Genotropin and Somatonorm. Acta Paediatr Scand Suppl 1987, 337: 118–21.

    Article  PubMed  CAS  Google Scholar 

  2. Moore JA, Rudman CG, MacLachlan NJ, Fuller GB, Burnett B, Frane JW. Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine. Endocrinology 1988, 122: 2920–6.

    Article  PubMed  CAS  Google Scholar 

  3. Pavia C. Spanish multicenter clinical trial of recombinant growth hormone produced in mammalian cells for treatment of growth failure due to idiopathic growth hormone deficiency. Spanish Multicenter Study Group. Horm Res 1992, 37 (Suppl 2): 22–7.

    Article  PubMed  Google Scholar 

  4. Strobl JS, Thomas MJ. Human growth hormone. Pharmacol Rev 1994, 46: 1–34.

    PubMed  CAS  Google Scholar 

  5. Stubbe P, Frasier SD, Stahnke N, et al. Growth response to recombinant human growth hormone of mammalian cell origin in prepubertal growth hormone-deficient children during the first two years of treatment. Horm Res 1992, 37 (Suppl 2): 28–36.

    Article  PubMed  Google Scholar 

  6. Zeisel HJ, von Petrykowski W, Wais U. Pharmacokinetics and short-term metabolic effects of mammalian cell-derived biosynthetic human growth hormone in man. Horm Res 1992, 37 (Suppl 2): 5–13.

    Article  PubMed  Google Scholar 

  7. Frasier SD, Lippe BM. Clinical review11: The rational use of growth hormone during childhood. J Clin Endocrinol Metab 1990, 71: 269–73.

    Article  PubMed  CAS  Google Scholar 

  8. Laron Z, Butenandt O. Optimum use of growth hormone in children. Drugs 1991, 42: 1–8.

    Article  PubMed  CAS  Google Scholar 

  9. Lippe BM, Nakamoto JM. Conventional and nonconventional uses of growth hormone. Recent Prog Horm Res 1993, 48: 179–235.

    PubMed  CAS  Google Scholar 

  10. Wilson DM. Clinical actions of growth hormone. Endocrinol Metab Clin North Am 1992, 21: 519–37.

    PubMed  CAS  Google Scholar 

  11. Annex Guideline on Similar Biological Medicinal Products containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues — Guidance on Similar Medicinal Products containing Somatropin (EMEA/ CHMP/94528/2005).

  12. Bierich JR. Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency. Acta Paediatr Scand Suppl 1987, 337: 135–40.

    Article  PubMed  CAS  Google Scholar 

  13. Bierich JR. Clinical experience with recombinant somatropin: German collaborative study. Acta Paediatr Scand Suppl 1988, 347: 184–6.

    PubMed  CAS  Google Scholar 

  14. De Muinck Keizer-Schrama S, Rikken B, Hokken-Koelega A, Wit JM, Drop S. Comparative effect of two doses of growth hormone for growth hormone deficiency. The Dutch Growth Hormone Working Group. Arch Dis Child 1994, 71:12–8.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Gunnarsson R, Wilton P. Clinical experience with Genotropin worldwide: an update March 1987. Acta Paediatr Scand Suppl 1987, 337: 147–52.

    Article  PubMed  CAS  Google Scholar 

  16. MacGillivray MH, Baptista J, Johanson A. Outcome of a four-year randomized study of daily versus three times weekly somatropin treatment in prepubertal naive growth hormone-deficient children. Genentech Study Group. J Clin Endocrinol Metab 1996, 81: 1806–9.

    CAS  Google Scholar 

  17. Maes M, Lindberg A, Price DA, et al. Long term growth response to growth hormone deficiencies: analysis of Kabi International Growth Study. In: Ranke MB, Gunnarson R, eds. Kabi International Growth Study biannual report No. 11. Mannheim, Germany: J. & J. Verlag, 1994.

    Google Scholar 

  18. Radetti G, Buzi F, Paganini C, Martelli C, Adami S. A four year dose-response study of recombinant human growth hormone treatment of growth hormone deficient children: effects on growth, bone growth and bone mineralization. Eur J Endocrinol 2000, 142: 42–6.

    Article  PubMed  CAS  Google Scholar 

  19. Ranke MB, Bierich JR. Clinical experience with authentic recombinant somatropin—German Collaborative Study. Acta Paediatr Scand Suppl 1987, 331: 9–17.

    Article  PubMed  CAS  Google Scholar 

  20. Rappaport R. Preliminary results of authentic recombinant somatropin treatment in human growth hormone deficient children. French Collaborative Study. Acta Paediatr Scand Suppl 1987, 331: 25–7.

    Article  PubMed  CAS  Google Scholar 

  21. Rappaport R, Mugnier E, Limoni C, et al. A 5-year prospective study of growth hormone (GH)-deficient children treated with GH before the age of 3 years. French Serono Study Group. J Clin Endocrinol Metab 1997, 82: 452–6.

    CAS  Google Scholar 

  22. Root AW, Kemp SF, Rundle AC, Dana K, Attie KM. Effect of long-term recombinant growth hormone therapy in children—the National Cooperative Growth Study, USA, 1985–1994. Journal of Pediatr Endocrinol Metab 1998, 11: 403–12.

    Article  CAS  Google Scholar 

  23. Takano K, Shizume K, Hibi I, et al. Treatment of hypopituitarism with recombinant somatropin for 1 year. Acta Paediatr Scand Suppl 1988, 347: 169–75.

    PubMed  CAS  Google Scholar 

  24. Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med 1999, 341: 1206–16.

    Article  PubMed  CAS  Google Scholar 

  25. Wilton P, Gunnarsson R. Clinical experience with Genotropin in growth hormone deficient children. Acta Paediatr Scand Suppl 1988, 343: 95–101.

    PubMed  CAS  Google Scholar 

  26. Ranke MB, Price DA, Reiter EO, eds. Growth hormone therapy in pediatrics — 20 years of KIGS. Basel, Switzerland: Karger, 2007, XV.

    Google Scholar 

  27. Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (Official Journal L 136, 30/4/2004, p. 85–90)

  28. Guideline on Similar Biological Medicinal Products containing Biotechnology-Derived Proteins as Active Substance: Quality Issues (EMEA/CHMP/49348/05).

  29. Guideline on Similar Biological Medicinal Products containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues (EMEA/CHMP/42832/05).

  30. Palczewska I, Niedzwiedzka Z. [Somatic development indices in children and youth of Warsaw]. Med Wieku Rozwoj 2001, 5 (2 Suppl 1): 18–118.

    PubMed  CAS  Google Scholar 

  31. Eiben O, Panto E. The Hungarian National Growth Standards. Anthrop Közl 1986, 30: 5–23.

    Google Scholar 

  32. Ranke MB, Haber P. Growth Hormone Stimulation Tests. In: Ranke MB, editor. Diagnostics of Endocrine Function in Children and Adolescents. 2 ed. Heidelberg, Leipzig: J. Ambrosius Barth (Edition J&J), 1996: 134–48.

    Google Scholar 

  33. Genotropin study TRN 86-073 (FDA, NDA 20-280, 24/8/1995).

  34. Tanner JM, Whitehouse RH, Takaishi, M. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965, Part II. Arc Dis Child 1966, 41: 613–35.

    Article  CAS  Google Scholar 

  35. Tanner JM, Whitehouse RH, Cameron N, et al. Assessment of Skeletal Maturity and Prediction of Adult Height (TW2 Method). London: Academic Press, 1983.

    Google Scholar 

  36. Prader A, Largo RH, Molinari L, Issler C. Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. Helv Paediatr Acta Suppl 1989, 52: 1–125.

    PubMed  CAS  Google Scholar 

  37. Greulich WW, Pyle, S.I. Radiographic atlas of skeletal development of hand and wrist. California: Stanford University Press, 1959.

    Google Scholar 

  38. Blethen SL, Allen DB, Graves D, August G, Moshang T, Rosenfeld R. Safety of recombinant deoxyribonucleic acidderived growth hormone: The National Cooperative Growth Study Experience. J Clin Endocr Metab 1996, 81: 1704–10.

    PubMed  CAS  Google Scholar 

  39. Lundin K, Berger L, Blomberg F, Wilton P. Developmentof anti-hGH antibodies during therapy with authentic human growth hormone. Acta Paediatr Scand Suppl 1991, 372: 167–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Children’s Memorial Health Institute, Warsaw, Poland

    T. Romer & M. Ginalska-Malinowska

  2. Department of Endocrinology, Buda Children’s Hospital, Budapest, Hungary

    F. Peter

  3. Department of Paediatrics, Albert Einstein College of Medicine, New York, USA

    P. Saenger

  4. Department of Paediatric Endocrinology, Polish-American Hospital, CMUJ, Krakow

    J. Starzyk

  5. Department of Paediatric Endocrinology and Diabetology, University Hospital, Katowice

    B. Koehler

  6. Department of Paediatric Endocrinology, Paediatric Institute, Poznan

    E. Korman

  7. Department of Paediatrics, Pomeranian Medical University, Szczecin

    M. Walczak

  8. Department of Paediatric Endocrinology, Paediatric Hospital, Wroclaw, Poland

    R. Wasik

  9. Department of Paediatrics, BAZ County Hospital, Miskolc, Hungary

    E. Solyom

  10. Sandoz Biopharmaceuticals, Keltenring 1 +3, D-82041, Oberhaching, Germany

    A. Berghout MD, PhD

Authors
  1. T. Romer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Saenger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Starzyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Koehler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Korman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Walczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Wasik
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Ginalska-Malinowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E. Solyom
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. Berghout MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Berghout MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Romer, T., Peter, F., Saenger, P. et al. Efficacy and safety of a new ready-to-use recombinant human growth hormone solution. J Endocrinol Invest 30, 578–589 (2007). https://doi.org/10.1007/BF03346352

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346352

Key-words

Search

Navigation