Original ArticleTen years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practiceDiez años de experiencia con el primer biosimilar autorizado de hormona del crecimiento recombinante humana en la práctica clínica habitual☆
Introduction
The European Medicines Agency (EMA) defines biosimilars as biopharmaceutical products that have been approved under a well-defined regulatory pathway and which are equivalent to biological medicines that have already been approved.1
The active substance of a biosimilar medicine is similar to the one of the biological reference medicine, although there are slight differences due to the natural complexity of biological products2 and to the methods employed in their manufacture (Fig. 1).3 For biosimilar medicines to be authorised, it must be proven that any differences between them and their reference medicines do not affect the safety or efficacy of treatment.2
The earliest treatments for patients with growth hormone deficiency (GHD) employed growth hormone extracted from cadaveric human pituitary glands (pit-GH). Although this achieved significant improvements in growth in treated patients, the use of pit-GH caused problems related to Creutzfeldt-Jakob disease. In the late 1980s, a biosynthetic growth hormone (GH) derived from recombinant DNA replaced pit-GH, providing a safe product without the previously observed problems and, being produced by biosynthesis, without the manufacturing restrictions that affected pit-GH, which depended on the availability of human pituitary glands. However, this biosimilar recombinant human growth hormone (rhGH) entailed a substantial increase in treatment cost.4
At present, most countries are facing restrictions in health care spending, and escalating health care costs are largely driven by novel high-cost biopharmaceutical agents. Thus, the main reason for the use of biosimilars is reducing treatment costs and facilitating access to these drugs. The uptake of biosimilars will depend on the degree to which cost savings are required by health care systems and the absolute savings that could be gained by switching from original drugs.1
The rhGH biosimilar was the first biosimilar approved by the EMA, which granted the authorisation in 2006 based on the quality, safety and efficacy demonstrated in bioequivalence studies comparing it to the reference product.1, 5, 6, 7
Based on the recommendations for the use of rhGH developed by the EMA, the biosimilar rhGH is authorised in Europe for the same indications as the reference product: GHD, growth disorders associated with Turner syndrome (TS), growth disorder associated with chronic renal insufficiency, Prader-Willi syndrome (PWS), growth disorder in children or adolescents born small for gestational age (SGA), and replacement therapy in adults with pronounced GHD.8
Section snippets
Materials and methods
We performed a review of the available literature on the clinical impact of biosimilar rhGH from its authorisation in 2006 to its current use in everyday clinical practice.
To do so, we performed a literature search in the PubMed database with the following criteria: articles published since 2010, studies in humans, in English or Spanish. We included the published scientific evidence with the highest impact, reviewed the clinical trials performed to obtain the authorisation for the drug, and the
Pre-authorisation studies
In accordance to the requirements of the EMA for the approval of a biosimilar rhGH, Romer et al.4 carried out a clinical trial that succeeded in achieving the first authorisation for the marketing of a biosimilar after presenting the results of the first 9 months of the trial, although the trial continued for a total followup of 7 years, demonstrating the long-term efficacy and safety of the product.8 Later on, López-Siguero et al.6 conducted another multicentre study, this time in Spain, which
Conclusions
Due to the global economic situation, governments have needed to cut health care spending, a circumstance that has promoted research and development of biosimilar medicines.1 In 2006, the EMA approved the first biosimilar rhGH, and from this moment, the number of patients treated with this medicine has growth progressively.9
The efficacy and safety of this drug have been assessed in equivalence trials, which demonstrated that they were comparable to those of the reference product and constituted
Funding
This study has been funded by Sandoz Farmacéutica SA.
Conflicts of interest
JPLS and MP have no conflicts of interest to declare. MPG, EMB and FJR are full-time employees of Sandoz Farmacéutica SA.
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Please cite this article as: López-Siguero JP, Palla García M, Martínez Busto E, Rebollo FJ, Pombo M. Diez años de experiencia con el primer biosimilar autorizado de hormona del crecimiento recombinante humana en la práctica clínica habitual. An Pediatr (Barc). 2018;88:209–215.