Original Article
Ten 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

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Abstract

Introduction

Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency.

Materials and methods

This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice.

Results

The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product.

Conclusion

The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug.

Resumen

Introducción

La hormona de crecimiento humana recombinante biosimilar (rhGH) fue el primer medicamento autorizado por la Agencia Europea del Medicamento (EMA), en el año 2006, por la vía de registro biosimilar. Se aprobó su uso para el tratamiento del déficit de hormona de crecimiento, trastorno de crecimiento asociado al síndrome de Turner, trastorno de crecimiento asociado a insuficiencia renal crónica, síndrome de Prader-Willi, trastorno de crecimiento en niños/adolescentes nacidos pequeños para su edad gestacional y como terapia de sustitución en adultos con deficiencia pronunciada de hormona de crecimiento.

Materiales y métodos

Esta revisión se centra en las evidencias científicas publicadas en los últimos 10 años, incluyendo los ensayos clínicos utilizados para conseguir la aprobación por parte de la EMA y los estudios más relevantes que evalúan el medicamento en la práctica clínica habitual.

Resultados

La equivalencia entre este biosimilar de rhGH y su producto de referencia ha sido demostrada en los ensayos clínicos publicados por Romer et al. y López-Siguero et al. Asimismo, los estudios del fármaco realizados en condiciones de práctica clínica habitual confirman su eficacia y seguridad a largo plazo, así como la ausencia de impacto clínico al cambiar el producto original por el biosimilar.

Conclusión

Desde su aprobación, el número de pacientes que reciben esta medicación ha experimentado un continuo crecimiento. Los datos preliminares del estudio postautorización PATRO indican que la eficacia y seguridad del fármaco se correlaciona con la obtenida en los ensayos clínicos. No obstante, aún queda pendiente evaluar los resultados definitivos del estudio que aportarán información adicional sobre la eficacia y seguridad del fármaco a largo plazo.

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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Cited by (0)

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.

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