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There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-naïve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was + 1.25 and + 1.35 in US and international patients, respectively. Conclusion: Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH. Trial registration: NA. What is Known: • Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies. • The PAtients TReated with Omnitrope® (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope®. What is New: • Omnitrope® is well tolerated and effective in US patients, and those from other countries. • Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes. [ABSTRACT FROM AUTHOR]

Background: Recombinant human growth hormone (rhGH, somatropin) therapy is approved in children with Prader-Willi syndrome (PWS)., Objectives: To report safety and effectiveness data for children with PWS treated with biosimilar rhGH (Omnitrope ® , Sandoz) in the PAtients TReated with Omnitrope (PATRO) Children study., Design: PATRO Children was a multicenter, non-interventional, postmarketing surveillance study., Methods: Children with PWS received Omnitrope according to standard clinical practice. Adverse events (AEs) were monitored for the duration of Omnitrope treatment. Effectiveness outcomes were also assessed, including height standard deviation (SD) scores (HSDS)., Results: As of July 2020 (study completion), 235 patients with PWS had been enrolled. At baseline, 95.7% ( n  = 225) of patients were prepubertal and 86.4% ( n  = 203) were rhGH treatment-naïve. At analysis, the median (range) treatment duration in the study was 56.8 (2.9-155.8) months. AEs were reported in 192 patients (81.7%) and were suspected as treatment-related in 39 patients (16.6%). Serious AEs (SAEs) were reported in 96 patients (40.9%) and were suspected as treatment-related in 22 patients (9.4%). The most frequent treatment-related SAEs were sleep apnea syndrome ( n  = 11; 4.7%), tonsillar hypertrophy ( n  = 4; 1.7%), and adenoidal hypertrophy ( n  = 4; 1.7%). Development of scoliosis was considered treatment-related in two patients; development of impaired glucose tolerance in one patient and type 2 diabetes mellitus in another patient were considered treatment-related. Effectiveness outcomes were primarily assessed in 153 patients who completed 3 years of treatment. Among the 151 prepubertal patients (135 treatment-naïve), mean (SD) change from baseline in HSDS after 3 years was +1.50 (1.07) across all patients and +1.57 (1.07) for treatment-naïve patients., Conclusion: These data suggest that biosimilar rhGH is well tolerated and effective in patients with PWS managed in real-life clinical practice. Patients with PWS should continue to be closely monitored for well-known safety issues (including respiratory, sleep, and glucose metabolism disorders, and scoliosis) during rhGH treatment., (© The Author(s), 2024.)

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. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. Methods PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. Results Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29–84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45–72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. Conclusions Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. Trial registration Not applicable.

Omnitrope® (somatropin, Sandoz Inc.) is one of several recombinant human growth hormones (rhGH) approved in the United States (US) for use in pediatric indications, including growth hormone deficiency (GHD) and idiopathic short stature (ISS). We report data on the effectiveness and safety of Omnitrope® in the US cohort of the PATRO Children (international, longitudinal, non-interventional) study. All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 US patients were recruited; the two largest groups were GHD (n=193) and ISS (n=62). Across all indications, HSDS improvement (ΔHSDS) from baseline at three years was +1.0 (rhGH-naïve, +1.2; pre-treated, +0.7). In pre-pubertal patients, ΔHSDS from baseline at three years was +0.94 (rhGH-naïve, +1.3; pre-treated, +0.7). Following three years of treatment, ΔHSDS from baseline was +1.3 in rhGH-naïve GHD patients and +1.1 in rhGH-naïve ISS patients. In pre-pubertal rhGH-naïve patients, ΔHSDS from baseline was +1.3 and +1.2 in GHD and ISS patients, respectively. Overall, 194 patients (66.0%) experienced adverse events (AEs; n=886 events); most were of mild-moderate intensity. Five patients (1.7%) had AEs that were suspected to be treatment-related (n=5 events). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No AEs of diabetes mellitus or hyperglycemia were reported. Omnitrope® appears to be well tolerated and effective in the majority of patients, without evidence of an increased risk of developing unexpected AEs, diabetes mellitus, or new malignancies during treatment. [ABSTRACT FROM AUTHOR]

Martin Schiestl,1 Markus Zabransky,2 Fritz Sörgel3,4 1Sandoz GmbH, Kundl, Austria; 2Sandoz Biopharmaceuticals, Hexal AG, Holzkirchen, Germany; 3Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany; 4Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany Abstract: A biosimilar is defined by the European Medicines Agency as a biological medicine that is similar to another biological medicine that has already been authorized for use. A science-based regulatory framework to ensure high-quality biosimilars has been established in Europe since 2005 and is monitored and updated on an ongoing basis. The guiding principle of a biosimilar development program is to establish similarity between the biosimilar and the reference medicine by the best possible means, ensuring that the previously proven safety and efficacy of the reference medicinal product also applies to the biosimilar. Development of a biosimilar is underpinned by state-of-the-art analytical techniques to characterize both reference medicines and biosimilars. The extent and nature of the nonclinical in vivo studies and clinical studies to be performed depend on the level of evidence obtained in the previous step(s), including the robustness of the physicochemical, biological, and nonclinical in vitro data. Extrapolation is an important element of the biosimilarity concept. When biosimilar comparability has been demonstrated in one indication, extrapolation of the data package to other indications of the reference medicine could be acceptable, but needs to be scientifically justified and considered in light of the demonstrated level of sameness by all analytical, nonclinical, and clinical data. The credibility of the scientific basis behind the biosimilar concept, and quality of regulatory decision-making, is demonstrated by the successful approval and clinical use of 20 biosimilar medicines since 2006 when Omnitrope® was the first biosimilar to be approved. The regulatory environment for biosimilars continues to evolve, both in recognition of advances in technology/analytical methods and the availability of new targets for biosimilar development. Keywords: biosimilars, regulatory pathways, Omnitrope®

Juan Pedro López-Siguero,1 Roland Pfäffle,2 Philippe Chanson,3 Mieczyslaw Szalecki,4,5 Nadja Höbel,6 Markus Zabransky6 1Servicio de Endocrinología Pediátrica, Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain; 2University Children’s Hospital Leipzig, Germany; 3Department of Endocrinology and Reproductive Diseases, Hôpital de Bicêtre, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris and University Paris-Sud, Le Kremlin-Bicêtre, France; 4Clinic of Endocrinology and Diabetology, Children’s Memorial Health Institute, Warsaw, Poland; 5Faculty of Medicine and Health Sciences UJK, Kielce, Poland; 6Sandoz Biopharmaceuticals, Hexal AG, Holzkirchen, Germany Abstract: In 2006, the European Medicines Agency (EMA) approved Omnitrope® as a biosimilar recombinant human growth hormone (rhGH), on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin®, Pfizer). Data continue to be collected on the long-term efficacy of biosimilar rhGH from several on-going postapproval studies. Particular topics of interest include efficacy in indications granted on the basis of extrapolation, and whether efficacy of growth hormone treatment is affected when patients are changed to biosimilar rhGH from other rhGH products. Data from clinical development studies and 10 years of postapproval experience affirm the clinical efficacy and effectiveness of biosimilar rhGH across all approved indications. In addition, the decade of experience with biosimilar rhGH since it was approved in Europe confirms the scientific validity of the biosimilar pathway and the approval process. Concerns about clinical effect in extrapolated indications, and also about the impact of changing from other rhGH preparations, have been alleviated. Biosimilar rhGH is an effective treatment option for children who require therapy with rhGH. Keywords: recombinant human growth hormone, Omnitrope®, biosimilar

Maria Victoria Borrás Pérez,1 Berit Kriström,2 Tomasz Romer,3 Mieczyslaw Walczak,4 Nadja Höbel,5 Markus Zabransky5 1Hospital General de Granollers, Granollers, Barcelona, Spain; 2Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden; 3Department of Endocrinology, Children’s Health Research Institute, Warsaw, 4Department of Paediatric Endocrinology and Diabetology, Pomeranian Medical University, Szczecin, Poland; 5Sandoz Biopharmaceuticals, Hexal AG, Holzkirchen, Germany Abstract: Safety concerns for recombinant human growth hormone (rhGH) treatments include impact on cancer risk, impact on glucose homeostasis, and the formation of antibodies to endogenous/exogenous GH. Omnitrope® (biosimilar rhGH) was approved by the European Medicines Agency in 2006, with approval granted on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin®). Additional concerns that may exist in relation to biosimilar rhGH include safety in indications granted on the basis of extrapolation and the impact of changing to biosimilar rhGH from other rhGH treatments. A substantial data set is available to fully understand the safety profile of biosimilar rhGH, which includes data from its clinical development studies and 10 years of post-approval experience. As of June 2016, 106,941,419 patient days (292,790 patient-years) experience has been gathered for biosimilar rhGH. Based on the available data, there have been no unexpected or unique adverse events related to biosimilar rhGH treatment. There is no increased risk of cancer, adverse glucose homeostasis, or immunogenic response with biosimilar rhGH compared with the reference medicine and other rhGH products. The immunogenicity of biosimilar rhGH is also similar to that of the reference and other rhGH products. Physicians should be reassured that rhGH products have a good safety record when used for approved indications and at recommended doses, and that the safety profile of biosimilar rhGH is in keeping with that of other rhGH products. Keywords: recombinant human growth hormone, Omnitrope®, biosimilar

Background: To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. Methods: PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. Results: Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29–84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45–72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. Conclusions: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Paul Saenger Division of Pediatric Endocrinology, Department of Pediatrics, Winthrop University Hospital, Mineola, NY, USA Abstract: Recombinant human growth hormone (rhGH) has been in clinical use for more than 30 years. With the expiration of patent exclusivity for the first wave of rhGH products and other biopharmaceuticals, the opportunity emerged for the development of biosimilar medicines. A biosimilar is defined by the European Medicines Agency (EMA) as a biological medicine that is similar to another biological medicine that has already been authorized for use. The EMA led the way (well ahead of the Food and Drug Administration in the US) in developing the biosimilar concept, and the type of science-based regulatory framework required to ensure high-quality, safe, and effective biosimilar medicines; the provisions for approval of biosimilars have been in place in Europe since 2005. Under these provisions, Omnitrope® was approved by the EMA in 2006 as the world’s first biosimilar medicine; 2016 therefore marks the 10th anniversary of its approval in Europe. A substantial data set, based on clinical development studies and 10 years of postapproval use, has now accumulated for biosimilar rhGH; this data set shows that the product is an effective treatment option for children who require rhGH treatment, and has a safety profile that is consistent with the rhGH class. The decade since the EMA approved biosimilar rhGH has seen the successful approval and clinical use of 20 biosimilar medicines, confirming the integrity of the scientific basis for the biosimilar concept, as well as the quality of regulatory decision-making. Keywords: recombinant human growth hormone, Omnitrope®, biosimilar

Background: PATRO Children is an ongoing observational, longitudinal, non-interventional, global post-marketing surveillance study, which is investigating the long-term safety and effectiveness of Omnitrope®, a somatropin biosimilar to Genotropin®, in children with growth disturbances. The primary endpoint of PATRO Children is long-term safety and the secondary endpoint is effectiveness, which is assessed by analysing auxological data such as height (HSDS) and height velocity (HVSDS) standard deviation scores. Here, we report the data from the Italian interim analysis of PATRO Children data up to August 2015. Methods: PATRO Children is enrolling children who are diagnosed with conditions of short stature requiring GH treatment and are receiving Omnitrope®. Adverse events (AEs) are assessed in all Omnitrope®-treated patients. Height is evaluated yearly to near-adult (final) height, and is herein reported as HSDS; height velocity is also assessed and reported as a standard deviation score (HVSDS). Results: Up to August 2015, a total of 186 patients (mean age 10.2 years, 57.5 % males) were enrolled :156 [84 %] had growth hormone deficiency, 12 [6.5 %] were born small for gestational age, seven [3.8 %] had Prader-Willi syndrome, one [0.5 %] had Turner syndrome and one [0.5 %] had chronic renal insufficiency; seven [3.8 %] patients had other indication profiles. The mean treatment duration with Omnitrope® was 28.1 ± 19.1 months. AEs were reported in 35.6 % of patients and included headache, pyrexia, arthralgia, abdominal pain, leg and/or arm pain and increased blood creatine phosphokinase. Two serious AEs in two patients were thought to be drug-related; one patient experienced a minimal increase in a known residual craniopharyngioma, and another a gait disturbance with worsening of walking difficulties. Similar to investigational studies, Omnitrope® treatment was associated with improvements in both HSDS and HVSDS. Conclusions: Omnitrope® appears to be well tolerated and effective for the treatment of a wide range of paediatric indications, which is consistent with the outcomes from controlled clinical trials. These results need to be interpreted with caution until the data from the global PATRO Children study are available. [ABSTRACT FROM AUTHOR]

Background: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePal™) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope® within routine clinical practice. Methods: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope® (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePal™, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients). Responses were based on a 5-point scale, with 2 being the best possible outcome and -2 the worst possible outcome. Results: In total, 550 patients were included in this study (338 from France, 169 from Germany, and 43 from the UK). The mean age ± standard deviation of participants was 10.8±3.5 years; the majority (57%) were male and growth hormone treatment naïve (88%). Almost half (49.8%) of children prepared their SurePal™ for injection themselves and 45.5% performed injections themselves. As patients progressed into their teens, the majority (&#880575%) favored preparing SurePal™ and performing injections themselves, rather than seeking assistance. The attractiveness of SurePal™ was rated as excellent/good by 84.7% of patients overall; this rating was similarly high (&#880579%) across countries and age-groups. Preparing (88.8%) and using (83.3%) SurePal™ were rated as very easy/easy by most patients; these ratings were similarly high, irrespective of country or age-group. The dose-memory function was rated as very helpful/helpful by 66.2% of patients. Among 246 patients who reported using the low drug-waste feature, 87.4% found it helpful. Among pretreated patients (n=64), 78.2% reported that SurePal™ was much better/ better than their previous device. Conclusion: These data confirm the ease of use and patient preference for SurePal? among pediatric patients with growth disturbances. [ABSTRACT FROM AUTHOR]

Close adherence to the recommended treatment regimen is important for the success of recombinant human growth hormone therapy, although nonadherence can be common. Ease of use and safety during use/storage are among several important factors in the design of a growth hormone injection device intended for long-term use. This study was performed to validate the usability and assess the ease of use of a new pen device (SurePal™) that has been developed to support daily administration of the recombinant human growth hormone product, Omnitrope® (somatropin). The primary objectives of the study were to assess if study participants, representing intended users of the pen in clinical practice, were able to perform an injection procedure into an injection pad effectively and safely and disassemble the pen without receiving a needlestick injury. A total of 106 participants (61 adults and 45 children/adolescents) were enrolled at two study centers (one in the US, one in Germany). Results for both primary usability tasks met the predefined acceptance criteria, with .85% of participants successfully performing each task. All of the other tasks/handling steps assessed were also successfully performed by most participants, with high success rates reflected in the high proportion of participants who classified each task as "very easy" or "easy". After a second use of the device, 87%-97% of participants rated it as "very easy" or "easy" to use. In summary, the new pen device is safe and easy to use for both adults and children, and will help to support effective, long-term daily administration of the recombinant human growth hormone product, Omnitrope®. [ABSTRACT FROM AUTHOR]

Objectives: Omnitrope ® (somatropin, Sandoz Inc.) is one of several recombinant human growth hormones (rhGH) approved in the United States (US) for use in pediatric indications, including growth hormone deficiency (GHD) and idiopathic short stature (ISS). We report data on the effectiveness and safety of Omnitrope ® in the US cohort of the PATRO Children (international, longitudinal, non-interventional) study., Methods: All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope ® are given according to country-specific prescribing information., Results: By September 2018, 294 US patients were recruited; the two largest groups were GHD (n=193) and ISS (n=62). Across all indications, HSDS improvement (ΔHSDS) from baseline at three years was +1.0 (rhGH-naïve, +1.2; pre-treated, +0.7). In pre-pubertal patients, ΔHSDS from baseline at three years was +0.94 (rhGH-naïve, +1.3; pre-treated, +0.7). Following three years of treatment, ΔHSDS from baseline was +1.3 in rhGH-naïve GHD patients and +1.1 in rhGH-naïve ISS patients. In pre-pubertal rhGH-naïve patients, ΔHSDS from baseline was +1.3 and +1.2 in GHD and ISS patients, respectively. Overall, 194 patients (66.0%) experienced adverse events (AEs; n=886 events); most were of mild-moderate intensity. Five patients (1.7%) had AEs that were suspected to be treatment-related (n=5 events). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No AEs of diabetes mellitus or hyperglycemia were reported., Conclusions: Omnitrope ® appears to be well tolerated and effective in the majority of patients, without evidence of an increased risk of developing unexpected AEs, diabetes mellitus, or new malignancies during treatment., (© 2020 Philippe Backeljauw et al., published by De Gruyter, Berlin/Boston.)

Background: A questionnaire-based survey was conducted to evaluate attitudes towards a reusable self-injection system, SurePal™, among paediatric patients with growth disturbances who were prescribed treatment with somatropin (Omnitrope ® ) as part of routine clinical practice., Methods: This cross-sectional survey was incorporated into the multinational, multi-centre, noninterventional PAtients TReated with Omnitrope ® (PATRO) Children study. Questions were mainly focused on five areas: the attractiveness of SurePal™; training received; use of the device; opinion of the low-drug wastage system; experience compared with previous devices used (among pretreated patients)., Results: Final results from participants in France are reported. Completed questionnaires were returned by 409 participants. Most patients (55%) were male and 89% were recombinant human growth hormone (rhGH)-treatment naïve. Around 57% of children completed the questionnaire by themselves, while 43% had help from a family member/other person. The mean (standard deviation) age of all participants was 11.3 (3.6) years, and most patients were aged 10-12 years ( n = 126) or 13-15 years ( n = 117). Overall, 86% of patients reported that preparing SurePal™ for injection was easy/very easy. Similarly, 83% reported that performing injections with SurePal™ was easy/very easy. The attractiveness of SurePal™ was rated as good/excellent by the majority (85%) of patients; this proportion was similarly high (> 80%) across all age groups. The dose-memory function was rated as helpful/very helpful by 54% of patients. Of the 174 patients who reported using the low drug-waste feature, 90% found it to be helpful/very helpful. Among the 24 pretreated patients, 17 reported that SurePal™ was better/much better than their previous device., Conclusions: This questionnaire-based survey conducted in a large cohort of paediatric patients with growth disturbances from France confirms the ease of use of SurePal™ to support daily administration of Omnitrope ® across all age groups. The demonstrated acceptability of the device may help to improve patient adherence to long-term daily treatment with rhGH., Competing Interests: Conflict of interest statement: RC has received speaker fees from Sandoz, Lilly, Merck, Pfizer and Novo Nordisk. The authors report no other conflicts of interest in this work.

Background: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePal™) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope(®) within routine clinical practice., Methods: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope(®) (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePal™, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients). Responses were based on a 5-point scale, with 2 being the best possible outcome and -2 the worst possible outcome., Results: In total, 550 patients were included in this study (338 from France, 169 from Germany, and 43 from the UK). The mean age ± standard deviation of participants was 10.8±3.5 years; the majority (57%) were male and growth hormone treatment naïve (88%). Almost half (49.8%) of children prepared their SurePal™ for injection themselves and 45.5% performed injections themselves. As patients progressed into their teens, the majority (≥75%) favored preparing SurePal™ and performing injections themselves, rather than seeking assistance. The attractiveness of SurePal™ was rated as excellent/good by 84.7% of patients overall; this rating was similarly high (≥79%) across countries and age-groups. Preparing (88.8%) and using (83.3%) SurePal™ were rated as very easy/easy by most patients; these ratings were similarly high, irrespective of country or age-group. The dose-memory function was rated as very helpful/helpful by 66.2% of patients. Among 246 patients who reported using the low drug-waste feature, 87.4% found it helpful. Among pretreated patients (n=64), 78.2% reported that SurePal™ was much better/better than their previous device., Conclusion: These data confirm the ease of use and patient preference for SurePal™ among pediatric patients with growth disturbances.

Close adherence to the recommended treatment regimen is important for the success of recombinant human growth hormone therapy, although nonadherence can be common. Ease of use and safety during use/storage are among several important factors in the design of a growth hormone injection device intended for long-term use. This study was performed to validate the usability and assess the ease of use of a new pen device (SurePal™) that has been developed to support daily administration of the recombinant human growth hormone product, Omnitrope® (somatropin). The primary objectives of the study were to assess if study participants, representing intended users of the pen in clinical practice, were able to perform an injection procedure into an injection pad effectively and safely and disassemble the pen without receiving a needlestick injury. A total of 106 participants (61 adults and 45 children/adolescents) were enrolled at two study centers (one in the US, one in Germany). Results for both primary usability tasks met the predefined acceptance criteria, with >85% of participants successfully performing each task. All of the other tasks/handling steps assessed were also successfully performed by most participants, with high success rates reflected in the high proportion of participants who classified each task as "very easy" or "easy". After a second use of the device, 87%-97% of participants rated it as "very easy" or "easy" to use. In summary, the new pen device is safe and easy to use for both adults and children, and will help to support effective, long-term daily administration of the recombinant human growth hormone product, Omnitrope®.

Objective: To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope(®)) for the treatment of children requiring growth hormone treatment., Methods: PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children's hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope(®) in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope(®) and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope(®) are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope(®) treatment in children short for gestational age (SGA); safety issues in patients with Prader-Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3., Results: As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope(®) treatment, no reports of malignancy and no safety issues in PWS patients., Conclusions: The efficacy and safety profile of Omnitrope(®) in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope(®), and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of rhGH in children born SGA, the risk of malignancies in children receiving rhGH, and AEs with a possible causal relationship to rhGH treatment in children with PWS.