Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope<sup>®</sup>): data from the PATRO Adults study

Beck‐Peccoz, Paolo; Höybye, Charlotte; Murray, Robert; Şimşek, Suat; Zabransky, Markus; Zouater, Hichem; Stalla, Günter

doi:10.1177/2042018820943377

Cited by 7 publications

(5 citation statements)

References 22 publications

(44 reference statements)

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“…The current analysis also includes 69 reports of malignancy events (in 60 patients). The occurrence of on-study malignancies in PATRO Adults has been reported previously (based on data from July 2018) [ 14 ]. While the data did not in general support a carcinogenic effect of rhGH in adults with GHD, an increased risk of second new malignancies in patients with previous cancer could not be excluded.…”

Section: Discussionmentioning

confidence: 85%

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

et al. 2021

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Purpose To evaluate safety and effectiveness of biosimilar recombinant human growth hormone (rhGH; Omnitrope®) in adults with growth hormone deficiency (GHD), using data from the PATRO Adults study. Methods PATRO Adults was a post-marketing surveillance study conducted in hospitals and specialized endocrinology units across Europe. The primary objective was to assess the safety of rhGH in adults treated in routine clinical practice. All adverse events (AEs) were monitored and recorded for the complete duration of Omnitrope® treatment. Effectiveness was evaluated as a secondary objective. Results As of January 2020, 1447 patients (50.9% male) had been enrolled from 82 centers in 9 European countries. Most patients had adult-onset GHD (n = 1179; 81.5%); 721 (49.8%) were rhGH-naïve at study entry. Overall, 1056 patients (73.0%) reported adverse events (AEs; n = 5397 events); the majority were mild-to-moderate in intensity. Treatment-related AEs were reported in 117 patients (8.1%; n = 189 events); the most commonly reported (MedDRA preferred terms) were arthralgia (n = 19), myalgia (n = 16), headache (n = 14), and edema peripheral (n = 10). In total, 495 patients (34.2%) had serious AEs (SAEs; n = 1131 events); these were considered treatment-related in 28 patients (1.9%; n = 35 events). Mean (standard deviation) IGF-I SDS increased from – 2.34 (1.47) at baseline to – 0.23 (1.65) at 12 months, and remained relatively stable thereafter (up to 3 years). Body mass index remained stable between baseline and 3 years. Conclusion Data from PATRO Adults indicate biosimilar rhGH (Omnitrope®) is not associated with any unexpected safety signals, and is effective in adults with GHD treated in real-world clinical practice.

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Section: Discussionmentioning

confidence: 85%

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

et al. 2021

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“…Therefore, the safety of biosimilar growth hormone products was carefully followed not only by routine pharmacovigilance but also by individual centers, networks of investigators, and registers, especially PATRO. The safety and efficacy profile turned out to be similar to the originator product [ 30 – 33 ].…”

Section: Resultsmentioning

confidence: 98%

Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience

et al. 2022

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The World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the ECBS considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence. The goal of this publication is to review the current clinical experience and scientific evidence and to provide an expert perspective for updating the WHO guidelines to provide more flexibility and clarity. As the first step, the relevant guidelines by other regulatory bodies were reviewed in order to identify issues that might help with updating the WHO guidelines. Next, a literature search was conducted for information on the long-term efficacy, safety, and immunogenicity of biosimilars to identify possible long-term problems. Finally, a search for articles concerning the role of clinical studies in the benefit–risk evaluation of biosimilars was conducted. The analysis of other guidelines suggested that the WHO guidelines may need more emphasis on the importance of the state-of-the-art physicochemical and structural comparability exercise and in vitro functional testing. The use of “foreign” reference product will also need clarifications. The value of in vivo toxicological tests in the development of biosimilars is questionable, and the non-clinical part needs revisions accordingly. The concepts of “totality of evidence,” “stepwise development,” and “residual uncertainty” were applied in the evaluation of the clinical sections of the guideline. The review of long-term safety and efficacy demonstrated the robustness of the current biosimilar development concept. The analysis of the roles of different development phases suggested that the large efficacy, safety, and immunogenicity studies are, in most cases, redundant. The residual uncertainty of safety, immunogenicity, and efficacy of biosimilars that has shaped the current regulatory guidelines is now substantially reduced. This will allow the re-evaluation of the non-clinical and clinical requirements of the current WHO main guideline. The shift of the relative impact of the development phases towards physico-chemical and in vitro functional testing will provide a relief to the manufacturers and new challenges to the regulators.

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“…No increased risk was seen for neoplasia compared with other GH treatments [ 124 ]. Further analysis from the same database including 1293 adults, of which 637 (49.3%) were GH treatment-naïve at study entry and the majority having multiple pituitary hormone deficiency ( n = 1128, 87.2%), demonstrated that GH treatment did not result in an increased cancer risk, although an increased risk of second new malignancies in patients with previous cancer could not be excluded [ 125 ]. Conversely, the SAGhE studies of GH therapy in young adults with childhood-onset GHD suggested an increased risk for certain cancer types or a trend towards increased risk of mortality with GH therapy [ 17 , 126 ].…”

Section: Gh Treatment In Cancer Survivors During Adulthoodmentioning

confidence: 99%

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

et al. 2021

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Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

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Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope^®): data from the PATRO Adults study

Cited by 7 publications

References 22 publications

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

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Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from the PATRO Adults study

Cited by 7 publications

References 22 publications

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults)

Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

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Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope^®): data from the PATRO Adults study