GP2017, an adalimumab biosimilar: pharmacokinetic similarity to its reference medicine and pharmacokinetics comparison of different administration methods.

Background: To compare the pharmacokinetics of Sandoz biosimilar adalimumab (GP2017) with reference adalimumab (Humira) in healthy volunteers (PK similarity study) and to compare the pharmacokinetics of GP2017 administered by autoinjector (AI) or prefilled syringe (PFS; delivery study). Methods: Healthy male subjects were randomized to receive a single 40 mg subcutaneous injection of GP2017, US-licensed or EU-authorized reference adalimumab (US/EU-Humira; PK similarity study) or a single 40 mg subcutaneous injection of GP2017 via AI or PFS (delivery study). Pharmacokinetics, safety, and immunogenicity were assessed over 72 days post-injection. Results: The geometric mean ratios (90% confidence intervals) for Cmax and AUC0-inf were 1.05 (0.99-1.11) and 1.04 (0.96-1.13) for GP2017/EU-Humira and 1.00 (0.94-1.06) and 1.08 (1.00-1.18) for GP2017/US-Humira, all within the prespecified margin of 0.80-1.25 (PK similarity study). Pharmacokinetic parameters of GP2017 matched between AI and PFS (delivery study). Safety and immunogenicity were similar across groups in both studies. Conclusion: PK similarity between GP2017, EU- and US-Humira was demonstrated. The safety profile of GP2017 was consistent with previous reports for Humira. These results contribute to the 'totality-of-the-evidence' supporting biosimilarity of GP2017 to Humira. PK and tolerability were equivalent for GP2017 dosed by AI or PFS. Trial registration: PK similarity study EudraCT no. 2015-000579-28; Delivery study: EudraCT no. 2014-002879-29.

Two-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age.

INTRODUCTION: This ongoing, prospective, open-label, non-comparative, multicenter phase IV study is evaluating the safety and efficacy of recombinant human growth hormone (rhGH; Omnitrope(®), Sandoz GmbH) in short children born small for gestational age (SGA). Here we report data from patients who have completed 2 years' treatment. METHODS: Eligibility criteria included prepubertal children born SGA with growth disturbances defined as current height standard deviation score (HSDS) <-2.5 and parental adjusted SDS <-1; birth weight and/or length <-2 SDS; and failure of catch-up growth [height velocity (HV) SDS <0 during the last year] by 4 years of age or later. The primary study objective is to assess the long-term effect of Omnitrope treatment on the development of diabetes in short children born SGA. Secondary objectives include evaluation of efficacy, incidence and severity of adverse events (AEs), occurrence of malignancies during treatment, and detection of anti-rhGH antibodies during treatment. RESULTS: In total, 278 children have been enrolled and received study medication; 249 have completed 2 years of treatment. No child has developed diabetes mellitus during the first 2 years; no fasting glucose or 2-h oral glucose tolerance test value exceeded the pre-defined limits of >126 or >200 mg/dL, respectively. No adverse alterations in body mass were noted. Treatment-emergent AEs were experienced by 211 (76.2%) children; most of these were of mild-to-moderate intensity (99.3%) and considered unrelated to study medication (97.6%). Treatment with Omnitrope was effective; mean HSDS was -3.39 at baseline, -2.57 at 1 year and -2.15 at 2 years of treatment. Mean HVSDS (peak-centered) also improved, from -2.13 at baseline to +4.16 at 1 year and +2.23 at 2 years. CONCLUSION: In this second interim analysis, short children born SGA were safely and effectively treated with rhGH (Omnitrope), and 2 years' treatment had no major adverse impact on carbohydrate metabolism or body mass. FUNDING: Sandoz.

One-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age.

BACKGROUND: This prospective, open-label, non-comparative, multicentre, long-term phase IV study is examining the efficacy and safety of somatropin [recombinant human growth hormone (rhGH)] in short children born small for gestational age (SGA) and its impact on the incidence of diabetes. This report is the first interim analysis of patients who have completed 1 year of treatment. METHODS: A total of 278 pre-pubertal patients were enrolled. Key eligibility criteria included height standard deviation score (HSDS) <-2.5; parental adjusted SDS <-1; birth weight and/or length <-2 SD and failure to show catch-up growth by ≥4 years of age. Patients were treated with rhGH 0.035 mg/kg/day. The primary objective was to evaluate the long-term effect of rhGH on carbohydrate metabolism [including fasting glucose, stimulated glucose (2-h oral glucose tolerance test, OGTT) and glycated haemoglobin (HbA1c)]. Secondary objectives included evaluation of height parameters [body height, HSDS, height velocity (HV), HVSDS]; insulin-like growth factor 1 (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) serum levels during treatment; and incidence and severity of adverse events (AEs). RESULTS: None of the children developed diabetes mellitus within the first year of treatment. Mean levels of fasting glucose, HbA1c and 2-h OGTT values remained stable during the study period. Treatment with rhGH was effective, as documented by all height parameters. Mean HSDS improved from -3.39 at baseline to -2.57 at Year 1. Mean HV increased markedly from 4.25 cm/year at baseline to 8.99 cm/year during the first year. Similarly, mean peak-centred HVSDS increased from -2.13 at baseline to +4.16 at Year 1. Mean IGF-I SDS and IGFBP-3 SDS also increased within the first year (by +1.80 and +0.41, respectively). 13 patients (4.7%) did not respond adequately to treatment (HVSDS <1); they were withdrawn from the study. In total, 192 children (69.3%) experienced treatment-emergent AEs; most (98.7%) were mild-to-moderate, and the majority (96.5%) were unrelated to study treatment. CONCLUSION: This interim analysis shows that short children born SGA can be effectively and safely treated with rhGH and that rhGH treatment has no major impact on carbohydrate metabolism after the first year of treatment.

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) in children requiring growth hormone treatment.

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.