Among patients with rheumatoid arthritis (RA) not responsive to tumor necrosis factor (TNF) inhibitors, CT-P10, a rituximab candidate biosimilar, has equivalent pharmacokinetics as compared with rituximab and similar efficacy, immunogenicity, and safety, according to a study published in the Annals of the Rheumatic Diseases.

While biologic agents have improved outcomes for many patients with RA, their high cost may render them inaccessible for some.1 As a result, biosimilar agents in development aim to provide similar benefits as existing biologics, but at a lower cost. In addition to pharmacokinetics and efficacy, biosimilars must also demonstrate comparable safety and immunogenicity as the innovator biologic reference product.

In this phase 1 trial (NCT01534884), Dae Hyun Yoo, MD, of Hanyang University for Rheumatic Diseases in Korea, and colleagues compared the pharmacokinetics, safety, and efficacy of CT-P10 with innovator biologic rituximab.2


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High Yield Data Summary

  • CT-P10 and rituximab were shown to have equivalent pharmacokinetics, pharmacodynamics, and immunogenicity in patients with RA up to 24 weeks

A total of 154 patients with RA either intolerant or with inadequate response to TNF inhibitors- were randomized in a 2:1 ratio to receive 1000 mg of either the CT-P10 biosimilar or rituximab reference product at week 0 and week 2 while receiving maintenance methotrexate.

The primary outcomes 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).” Data and outcomes were collected for up to 24 weeks.

Pharmacokinetic (PK) equivalence was demonstrated if the 90% confidence intervals (CIs) for the ratio of geometric means (CT-P10/RTX) for both primary outcomes were within the bioequivalence range of 80% to 125%.

CT-P10 met the predefined criteria for PK equivalence, with the 90% CIs for the ratio of geometric means (CT-P10/RTX) falling within the bioequivalence range for AUC0–last (97.7%; 90% CI, 89.2% to 107.0%) and Cmax (97.6%; 90% CI, 92.0% to 103.5%).

At 24 weeks, overall disease activity scores and changes in disease activity from baseline were similar between the CT-P10 and rituximab treatment groups.

Antidrug antibodies (ADAs) and neutralizing antibodies were detected in similar proportions of patients in both treatment groups (17.6% and 2.0%, respectively).

“In the current study, no significant effects of ADAs on efficacy were observed although numerical reductions in response rates (of around the same magnitude) were noted in both treatment groups,” the authors noted. “Presence of ADAs did not affect the safety of either drug,” they added.

No significant differences in the rates of adverse events were found between the groups. Infusion-related reactions were generally mild, with only one headache reportedin the CT-P10 group.

Summary and Clinical Applicability

Researchers compared the pharmacokinetics, safety, and efficacy of CT-P10, a rituximab candidate biosimilar, with innovator rituximab in patients with RA refractory to TNF inhibitors in this phase 1 trial. Pharmacokinetic equivalence was the primary outcome, although disease activity measures, the development of antidrug antibodies, and adverse effects were also assessed.

“In this study, CT-P10 and RTX demonstrated equivalent PK and comparable efficacy, [pharmacodynamics], safety and immunogenicity up to week 24 in patients with RA,” the authors concluded. “The results provide a clear rationale for future studies of CT-P10.”

Limitations and Disclosures

  • With a small sample size, this study was not powered to detect any but the largest differences in safety and efficacy between the CT-P10 and rituximab groups

  • Using a more sensitive electrochemiluminescent immunoassay may have resulted in higher rates of ADAs in both groups (17.6% for both) than are reported in the literature for rituximab (12.7%)

This study was funded by CELLTRION, the manufacturer of CT-P10.

References

  1. Dörner T, Strand V, Castañeda-Hernández G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72(3):322-8.

  2. Yoo DH, Suh CH, Shim SC, Jeka S, et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann Rheum Dis.  2016 Sep 13. doi: 10.1136/annrheumdis-2016-209540 [Epub ahead of print]

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