Pharmacokinetics and pharmacodynamics of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta® in healthy subjects: a randomized, double-blind trial

Purpose: MSB11455 is a proposed biosimilar to the reference pegfilgrastim (Neulasta®). This pivotal equivalence study (NCT03251248) assessed the pharmacokinetic and pharmacodynamic equivalence of MSB11455 to the reference product. Methods: This 2-way, 2-sequence, group-sequential, crossover study was conducted in healthy subjects. Subjects received a single subcutaneous dose of MSB11455 or the reference product (both 6 mg/0.6 mL) on Day 1 of each study period. Pharmacokinetic and pharmacodynamic (absolute neutrophil count; ANC) samples were taken predose and up to day 16 post-dose. Non-compartmental parameters were calculated. Immunogenicity samples were taken pre-dose and up to day 84 after the first dose. Safety was assessed throughout the study. Findings: A total of 292 subjects were randomized to therapy and treated; 244 received both treatments. For all primary pharmacokinetic and pharmacodynamic parameters, 90% repeated confidence intervals of geometric means ratio of MSB11455 to the reference product were within the pre-defined equivalence range (80.00%–125.00%) for AUC (96.59–112.82); AUC (97.29–113.96), C (97.13–114.99), maximum observed effect on ANC (98.74–102.39), and area under the effect–time curve from time zero to time to last quantifiable concentration (97.30–100.23). Safety, tolerability, and immunogenicity were comparable between treatments. No filgrastim-specific neutralizing antibodies were detected with either treatment sequence. Implications: Pharmacokinetic and pharmacodynamic equivalence of MSB11455 and the reference product was shown, with comparable immunogenicity, safety, and tolerability between treatments. The study supports the biosimilarity of MSB11455 to the reference product. ClinicalTrials.gov identifier: NCT03251248

A Comparison of the Safety and Efficacy of HX575 (Epoetin Alfa Proposed Biosimilar) with Epoetin Alfa in Patients with End-Stage Renal Disease.

BACKGROUND: HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia. METHODS: This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28). RESULTS: Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was -0.093 g/dL, with 90% CI (-0.23 to 0.04) entirely within the pre-specified equivalence limits (-0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies. CONCLUSIONS: SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety