A large multicentre, randomized, double-blind, cross-over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US- and EU-reference biologics.

AIMS: Recombinant PEGylated human granulocyte colony-stimulating factor (pegfilgrastim) is indicated for the reduction of chemotherapy-induced neutropenia and prevention of febrile neutropenia. Biosimilar pegfilgrastim is expected to reduce the financial burden of this complication of chemotherapy. The aim of this study was to demonstrate biosimilarity between Sandoz biosimilar pegfilgrastim and its US- and EU-approved reference biologics. METHODS: Phase I, randomized, double-blind, single-dose, 3-period, 6-sequence cross-over, multicentre study to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of Sandoz biosimilar pegfilgrastim with US- and EU-references in healthy adults. RESULTS: Pharmacokinetic and pharmacodynamic similarity was demonstrated between the 3 biologics, as the 90% confidence interval for all primary pharmacokinetic and pharmacodynamic endpoint comparisons were contained within the predefined similarity margins of 0.80-1.25. Safety, immunogenicity and tolerability were also similar. CONCLUSIONS: Sandoz biosimilar pegfilgrastim demonstrated pharmacokinetic and pharmacodynamic similarity to both US- and EU-reference biologics. No meaningful differences in safety, local tolerability and immunogenicity were identified.

Safety and Effectiveness of a Biosimilar Recombinant Human Growth Hormone in Children Requiring Growth Hormone Treatment: Analysis of Final Data from PATRO Children, an International, Post-Marketing Surveillance Study.

Purpose: Omnitrope® (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope® (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients. Methods: The study population included all pediatric patients treated with Omnitrope® (biosimilar rhGH), administered via daily injection, in routine clinical practice. The primary objective was to assess long-term safety, with effectiveness assessed as a secondary objective. Results: In total, 7359 patients were enrolled and treated in the PATRO Children study; 86.0% were treatment-naïve at baseline. Growth hormone deficiency was the most frequent indication (57.9%), followed by patients born small for gestational age (SGA; 26.6%). The mean (SD) duration of exposure to biosimilar rhGH was 3.66 years (2.39). A total of 16,628 adverse events (AEs) were reported in 3981 (54.1%) patients, most of which were mild/moderate. AEs suspected to be treatment related occurred in 8.3% of patients, most frequently headache (1.6%), injection-site pain (1.1%), or injection-site hematoma (1.1%). The incidence rate (IR) of type 2 diabetes mellitus was 0.11 per 1000 person-years (PY) across all patients, and 0.13 per 1000 PY in patients born SGA. The IR of newly diagnosed primary malignancies was 0.22 per 1000 PY across all patients. In the 6589 patients included in the effectiveness population, a sustained catch-up growth was observed across all indications. After 5 years of treatment, height SDS increased from baseline by a median (range) of +1.79 (-3.7 to 6.2) in treatment-naïve patients and +0.73 (-1.4 to 3.7) in pretreated patients. Conclusion: This final analysis of the PATRO Children study indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice. These data are consistent with the well-characterized safety profile of rhGH treatment in pediatric patients.