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Pituitary Disorders
changes to the manufacturing process due to increasing production continued for up to seven years.
9,10
Results showed that in terms of
scale, improving product stability or moving production to another safety profile and efficacy, Omnitrope was therapeutically similar to
site must not change the comparability level. A manufacturer must Genotropin and, according to the data from literature, to other
provide evidence that the procedural changes did not adversely preparations of rhGH such as Saizen and Norditropin.
11–17
affect the quality of the product.
Conclusion
The final ‘comparability exercises’ include the clinical phase III The process of developing Omnitrope was planned to fulfil the
study. The aim of the phase III clinical study was to compare rigorous demands of the EMEA centralised registration procedure.
Omnitrope with the reference product and to assess its long-term It has created an opportunity to excel in the production of
safety and efficacy. To meet this aim, a population of 89 children high-quality biopharmaceuticals.
with idiopathic GH deficiency diagnosed in accordance to the
worldwide accepted criteria were randomised to Omnitrope group In the past 25 years significant advances in analytical technology
A (n=44) or Genotropin group B (n=45). The patients were GH-naïve. have been seen. These have allowed the establishment of new
comparability assessments for comparison of the new version of
biopharmaceutical to the reference product. The consistency and
comparability of Omnitrope with the reference product in terms of
The process of developing Omnitrope physicochemical protein structure, biological activity, toxicity and
was planned to fulfil the rigorous
tolerance have been proved in pre-clinical studies. Similar PK, PD
and safety profiles to the reference product in phase I clinical
demands of the EMEA centralised studies have been proved. Long-term phase III clinical studies have
registration procedure.
demonstrated therapeutically comparability with the reference
product, clinical efficacy and safety, as well as low immunogenicity.
Therefore, Omnitrope, being fully similar to the reference product,
In the study, a lyophilised Omnitrope formulation was used, as the is approved in Europe for a wide range of indications: GH deficiency
reference product was of the same formulation. The study in children and adults, Turner syndrome, chronic renal insufficiency,
comparing Omnitrope with the reference product was carried out children small for gestational age and Prader-Willi syndrome.
for nine months; the first six months is the period of treatment with Patients living in Europe, the US, Canada, Japan, Australia and all
the most intense growth response to GH – the so-called catch-up other countries where Omnitrope has received marketing approval
period. Moreover, selected GHD-naïve pre-pubertal children were have gained a new valuable, more affordable recombinant hGH. n
the population most sensitive to GH. A study planned in this way is
considered to be the best model to detect any differences between
Tomasz E Romer is an endocrinologist in private
GH preparations. Randomised groups were similar for all auxological
practice in Warsaw. Prior to this he was Head of the
parameters before the treatment was started. There were no Department of Endocrinology at the Child Health
significant statistical differences between the groups in any of the
Memorial Research Institute in Warsaw, where he also
founded a Paediatric Endocrinology Unit. Professor
time-points assessed during the treatment period (three, six and
Romer has been a member of the European Society of
nine months of the treatment; see Paediatric Endocrinology since 1985 and was PresidentFigures 2 and 3). Adverse
reactions observed in patients did not differ between the groups.
and organiser of the 38th Annual Meeting in Warsaw in
1999. He has also been principal investigator in the
pre-registration clinical trials of Maxomate (Sanofi), Accretropin (Cangene), Valtropine
To assess the long-term safety and efficacy of both formulations of (Biopartners) and Omnitrope (Sandoz). Professor Romer obtained his PhD in 1964 and
Omnitrope – the lyophilised and the more convenient ready-to-use
his professorship in 1985.
liquid formulation – the study of the same group of patients was
1. Miller WL, Baxter JD, Recombinant DNA – a new source 10 Years’ Experience, Heidelberg, Leipzig: Johann Collaborative Group, Acta Paediatr Scand Suppl,
of insulin, Diabetologia, 1980;18:431–6. Ambrosius Barth Verlag, 1999. 1988;347:180–83.
2. Dean HJ, Friesen HG, Growth therapy in Canada: end of 9. Romer T, Peter F, Saenger P, Starzyk J, Koehler B, Korman 14. De Muinck Keizer-Schrama S, Rikken B, Hokken-Koelega
one ere and beginning of another, Can Med Assoc J, E, Walczak M, Efficacy and safety of a new ready-to-use A, et al., Comparative effect of two doses of growth
1986;135:297–301. recombinant human growth hormone solution, J hormone for growth hormone deficiency. The Dutch
3. Takano K, Shizume K, Hizuka N, et al., Treatment of Endocrinol Invest, 2007;30:578–89. Growth Hormone Working Group, Arch Dis Child, 1994;71:
idiopathic pituitary dwarfism with methionyl human 10. Romer T, Saenger P, Peter F, et al., Seven years of safety 12–18.
growth hormone, Endocrinol Jpn, 1983;30:523–7. and efficacy of the recombinant human Growth 15. Bercu BB, Murray FT, Frasier SD, et al., Long-term
4. Kaplan SL, Undrewood LE, August GP, et al., Clinical Hormone Omnitrope
®
in the treatment of Growth therapy with recombinant human growth hormone
studies with recombinant-DNA-derived methionyl Hormone Deficient children: results of a phase III study, (Saizen) in children with idiopathic and organic growth
human growth hormone in growth hormone deficient Hormone Res, 2009; in press. hormone deficiency, Endocrine, 2001;15:43–9.
children, Lancet, 1986;1:697–700. 11. Coste J, Letrait M, Carel JC, et al., Long-term results of 16. Root AW, Kemp SF, Rundle AC, et al., Effect of long-term
5. Girard F, Gourmelen M, Clinical experience with growth hormone treatment in France in children of recombinant growth hormone therapy in children-the
Somatonorm, Acta Paediatr Scand Suppl, 1986;325:29–32. short stature: population, register based study, BMJ, National Cooperative Growth Study, USA, 1985–1994,
6. Milner RD, Clinical experience of somatrem: UK 1997;315:708–13. J Pediatr Endocrinol Metab, 1998;11:403–12.
preliminary report, Acta Paediatr Scand Suppl, 1986;325: 12. Cohen P, Bright GM, Rogol AD, et al., Effects of dose and 17. Reiter EO, Price DA, Wilton P, et al., Effect of growth
25–8. gender on the growth and growth factor response to GH hormone (GH) treatment on the near-final height of 1258
7. Bierich JR, Treatment of pituitary dwarfism with in GH-deficient children: implications for efficacy and patients with idiopathic GH deficiency: analysis of a
biosynthetic growth hormone, Acta Paediatr Scand Suppl, safety, J Clin Endocrinol Metab, 2002;87:90–98. large international database, J Clinl Endocrinol Metab,
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50 EUROPEAN ENDOCRINOLOGY
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