A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis

Abstract

ObjectiveTo demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.MethodsIn this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration–time curve from time zero to last quantifiable concentration (AUC0–last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.Results103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%–125% (AUC0–last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.ConclusionsCT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.Trial registration numberNCT01534884.

Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial

“…PK results in this study were similar to those observed in a Phase 1 study comparing CT-P10 to EU-RTX. 10 Importantly, in this report the PK was also shown to be equivalent between CT-P10 and US-RTX. Considering the equivalence of EU-RTX and US-RTX shown in Part 1, it is appropriate to assess efficacy equivalence of CT-P10 against a combined RTX group, where both PK and efficacy of CT-P10 could be considered “as equivalent” to each form of RTX as each of these reference products was to each other.…”

“…We are therefore satisfied that there is sufficient assurance that individual PK concentration levels seen with CT-P10 and reference products are likely due to random fluctuations, and not any intrinsic properties of either drug. 10 …”

“…CT-P10 and RTX share an identical primary structure and have highly similar higher-order structures, post-translational modifications, and in vitro activities. 10 A Phase 1 study of CT-P10 in patients with RA demonstrated equivalent PK to European Union-sourced RTX (EU-RTX; MabThera®; Roche, Welwyn Garden City, UK) and comparable efficacy, pharmacodynamics (PD), immunogenicity, and safety up to week 72. 10–14 CT-P10 and United States-sourced RTX (US-RTX; Rituxan®; Genentech, Inc., South San Francisco, USA) have also been shown to be similar in patients with follicular lymphoma, a B cell-related hematological malignancy for which RTX is approved.…”

Rituximab in the treatment of follicular lymphoma: the future of biosimilars in the evolving therapeutic landscape

“…A study in patients with newly diagnosed advanced FL showed pharmacokinetic similarity between a potential biosimilar to rituximab, CT-P10, and rituximab (each administered with CVP), with similar B-cell kinetics and immunogenicity 45. In another study, CT-P10 and rituximab showed equivalent pharmacokinetics, and comparable efficacy, pharmacodynamics, immunogenicity, and safety in patients with RA 46. A clinical study in patients with previously untreated FL showed therapeutic equivalence in overall response rate between another proposed biosimilar to rituximab, GP-2013, and rituximab sourced from the EU.…”

A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability

“…At week 102, ACR20, ACR50, and ACR70 response rates were 71.8%, 51.4%, and 26.1% in the switch (from INX to CT-P13) group and 71.7%, 48%, and 24.3% in the maintenance group, respectively. The response rates were maintained from weeks 54 to 102 in both groups 33. In this case, the proportion of patients reporting at least one TEAE was more balanced between the maintenance and the switch group (63.5% vs 62.2%), as well as the rate of TEAEs classified as related to treatment (22% vs 18.9%), and the incidence of infusion-related reaction (6.9% vs 2.8%), latent tuberculosis (5.7% vs 2.8%), upper respiratory tract infection (3.8% vs 2.1%), lower respiratory tract infection (2.5% vs 2.8%), abnormal liver function test (0.6% vs 2.8%), and urinary tract infection (1.3% vs 1.4%) 33…”