A recent international, randomized, double-blind study comparing the proposed biosimilar GP2013with both the reference rituximab approved in the European Union and in the United States found that GP2013 demonstrated 3-way pharmacokinetic and pharmacodynamic equivalence with both products in patients with rheumatoid arthritis.
A recent international, randomized, double-blind study comparing the proposed biosimilar GP2013 (Sandoz’s Rixathon) with both the reference rituximab (RTX) approved in the European Union (EU) (Roche’s MabThera) and in the United States (Genetech’s Rituxan) found that GP2013 demonstrated 3-way pharmacokinetic (PK) and pharmacodynamic (PD) equivalence with both products in patients with rheumatoid arthritis (RA). Efficacy, safety, and immunogenicity profiles were similar between GP2013 and the innovator products, according to the study sponsored by Sandoz and published in Annals of the Rheumatic Diseases.
The study involved 312 patients—randomized to receive GP2013, RTX-EU, or RTX-US reference product, along with methotrexate and folic acid—who had active RA despite prior tumor necrosis factor-alpha—inhibitor therapy. The study’s primary PK endpoint was the area under the serum concentration-time curve (AUC) from study drug infusion to infinity (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity, and safety outcomes, were also assessed up to week 24 of the study. To claim bioequivalence, the 90% confidence interval (CI) of the ratio of the geometric mean AUCs had to fall within the predefined range of 80% to 125%.
The main efficacy objective was to show non-inferiority of GP2013 to the reference rituximab products in terms of change from baseline in 28-joint disease activity score (DAS28) using C-reactive protein (CRP) at week 24. Other secondary efficacy objectives included the American College of Rheumatology (ACR) response rates, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and the Health Assessment Questionnaire Disability Index (HAQ-DI). The main PD parameter was peripheral CD19-positive B-cell count relative to baseline, up to the second infusion (AUEC0-14d). The researchers also assessed anti-drug antibodies (ADAs) to evaluate immunogenicity.
The rate of all adverse events (AEs), AEs related to the study medication, AEs leading to study drug discontinuation, serious AEs, and infusion-related reactions were similar between the treatment arms. The rate of ADAs was 16.5% in the GP2013 group versus 15.1% in the reference group up to the last patient visit—a majority of ADAs were transient. Five patients in the GP2013 arm and 1 patient in the RTX arm had neutralizing ADAs.
The researchers conclude that their study is part of the stepwise demonstration of similarity of the proposed biosimilar GP2013, and reference rituximab. “The primary objective of the study was met by demonstrating 3-way PK bioequivalence of GP2013, RTX-EU and RTX-US,” the authors said, and that their data are in line with previously published data on rituximab. The study also met its main efficacy objective by demonstrating non-inferiority of GP2013 versus RTX in terms of DAS28 CRP change from baseline at week 24. “Overall, the treatment effect was numerically greater in the current study as compared with the historic data, while efficacy was similar among the treatment arms in the current study,” they concluded. There were no relevant differences in the rate or severity of AEs among treatment arms. The researchers said that comparison of the rate of ADAs between studies is challenging because of differences of assay methodology, but the data observed were generally consistent with data in the literature, and the rate of ADAs in this study was similar between GP2013 and the reference rituximab.
In summary, the researchers concluded that their study met its primary objective by demonstrating 3-way bioequivalence of GP2013, RTX-EU, and RTX-US. The study also demonstrated 3-way PD equivalence, and GP2013 and reference rituximab were shown to be similar in terms of efficacy, safety, and immunogenicity.