Drug Design, Development and Therapy (Dec 2024)
Safety and Effectiveness of a Biosimilar Recombinant Growth Hormone in Adults with Growth Hormone Deficiency: Analysis of Final Data from PATRO Adults, an International Post-Marketing Surveillance Study
Abstract
Paolo Beck-Peccoz,1 Charlotte Höybye,2 Suat Simsek,3 Günter Stalla,4 Robert D Murray,5 Altaher Esmael,6 Dragan Urosevic,7 Anca Boldea,6 Markus Zabransky6 1Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Department of Endocrinology and Department of Molecular Medicine and Surgery, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden; 3Department of Internal Medicine/Endocrinology, Northwest Clinics, Alkmaar and Amsterdam University Medical Centers, Location VUmc, Amsterdam, The Netherlands; 4Medicover Neuroendocrinology and Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Munich, Germany; 5Leeds Centre for Diabetes & Endocrinology, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 6HEXAL AG (a Sandoz company), Holzkirchen, Germany; 7Novartis Sandoz Biopharmaceutical AG, c/o HEXAL AG, Basel, SwitzerlandCorrespondence: Paolo Beck-Peccoz, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico, Via Pietro Custodi 1, Milan, 20136, Italy, Tel +39 3357073239, Email [email protected]: Long-term studies are needed to investigate the safety of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) in routine practice. The objective of this study was to evaluate the safety and effectiveness of biosimilar rhGH (somatropin; Omnitrope®) in adults with GHD.Methods: PAtients TReated with Omnitrope (PATRO) Adults was a post-marketing surveillance study conducted across Europe. The primary objective was the safety of biosimilar rhGH in adults, particularly the occurrence of glucose intolerance or diabetes mellitus and malignancies. All adverse events (AEs) were recorded throughout treatment. Treatment effectiveness was a secondary objective.Results: By December 2021, 1527 patients (50.3% male) were enrolled from 84 centers in 10 European countries. Most patients had adult-onset GHD (n = 1243; 81.4%) and 771 (50.5%) were rhGH-naïve at study entry. Median (interquartile range) treatment duration was 4.4 (1.90– 7.30) years. Overall, 1181 patients (77.3%) reported 6667 AEs. Treatment-related AEs were reported in 143 patients (9.4%; 216 AEs); arthralgia was most common (n = 24). There were 49 confirmed diabetes mellitus events; 44 in newly diagnosed patients. Overall, 84 malignancies were reported. There were 46 treatment-related serious AEs in 39 patients (2.6%). The most frequently reported treatment-related serious AE was “metabolism and nutrition disorders” (n = 12). In rhGH-naïve patients, an increase in mean insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) was observed from – 2.03 at baseline to +0.28 at 5 years. An increase in IGF-1 SDS was also observed in previously treated patients from – 0.71 to +0.35. Body mass index remained stable while blood lipid levels improved from baseline to 5 years.Conclusion: Final data from PATRO Adults confirm that biosimilar rhGH (Omnitrope) is not associated with any unexpected safety signals, with no evidence of increased diabetogenic or carcinogenic risk, and is effective in real-world clinical practice.Plain language summary: Why was the study done?– Growth hormone deficiency is a condition caused by insufficient amounts of growth hormone in the body, which can be treated with daily injections of a replacement growth hormone medicine.– It is important to monitor the safety of long-term treatment with growth hormone, especially regarding the risk of cancer and diabetes.What did the researchers do?– The PATRO Adults study included adult patients with growth hormone deficiency who were treated with a growth hormone medicine called Omnitrope.– The researchers main aim was to evaluate specific safety concerns, including any potential increased risk of cancer and diabetes.What did the researchers find?– A total of 1527 patients were enrolled in the study.– Overall, 143 patients had an adverse reaction that was considered to be related to growth hormone treatment, the most common of which was arthralgia, a type of joint ache, which occurred in 1.6% of patients.– Overall, 17 patients (1.1%) developed diabetes and four patients (0.3%) developed cancer that was suspected as being related to growth hormone treatment.– The risk of developing diabetes and cancer was low and comparable to what has been seen in previous studies in patients treated with growth hormone.What do the results mean?– The safety findings from this study were consistent with the well characterized safety profile of growth hormone treatment in adults with growth hormone deficiency. This supports previous studies showing no evidence of increased risk of cancer or diabetes with growth hormone treatment in adults.Keywords: somatropin, long-term, real-world, European, diabetes, malignancy
