CT-P10 Shows Long-Term Similarity to EU and US Reference Rituximab in RA

Celltrion and Teva’s rituximab biosimilar, CT-P10, was recently approved in the United States under the brand name Truxima. Because of issues related to intellectual property, the drug received approval only in oncology indications. However, the biosimilar, like its reference, is approved in other regulatory territories for the treatment of inflammatory diseases, including rheumatoid arthritis (RA); B cells play a significant role in the pathogenesis of RA, and rituximab depletes CD20-expressing B cells. New research, published in BioDrugs, underscores the long-term efficacy and safety of treating RA with CT-P10.

The randomized, double-blind, active-controlled, parallel-group phase 3 study was conducted in 372 adult patients with RA at 76 centers as a continuation of a 24-week phase 3 study of the biosimilar compared with its EU and US reference products. Results of the initial study have been reported elsewhere. The current paper reports results up to week 48.

The patients were randomized to receive CT-P10 (n = 161), the US reference (n = 151), or the EU reference (n = 60).

Mean decreases from baseline in disease activity score in a count of 28 joints with erythrocyte sedimentation rate (DAS28-ESR) were similar among groups up to week 48; mean decreases were −2.9 (± 1.3) in the CT-P10 group and −2.8 (± 1.4) in the combined reference groups.

Improvements in disease activity as mean decreases from baseline in DAS28 measured with C-reactive protein (DAS28-CRP) were also similar. At week 48, the mean decreases in DAS28-CRP from baseline were −2.7 (± 1.2) in the CT-P10 group and −2.6 (± 1.3) in the combined reference groups.

Similar proportions of patients achieved clinical response according to American College of Rheumatology (ACR) criteria for 20%, 50%, and 70% improvement. At week 48, ACR20, ACR50, and ACR70 response rates were 80.6%, 55.4%, and 31.7%, respectively, in the CT-P10 group and 79.8%, 53.9%, and 33.7% in the combined reference group.

As measured by European League Against Rheumatism (EULAR) criteria, at week 48, the proportions of patients with good or moderate EULAR responses were 82.6% and 89.9%, respectively, in the CT-P10 group versus 83.8% and 87.0% in the combined reference group.

Low disease activity was achieved by 17.3% of patients in the CT-P10 group and by 11.4% of patients in the combined reference groups at week 48. Similarly, by week 48, 17.3% of patients in the CT-P10 group and 22.8% of patients in the combined reference group achieved remission.

In terms of patient-reported outcomes, the mean health assessment questionnaire disability index score decreased from baseline to week 48 in all groups, and scores were comparable for physical, mental, and other components among groups.

In terms of radiographic progression, at week 48, the mean increase in baseline Van der Heijde modified total sharp score was 1.8 (± 8.9) in the CT-P10 group and 1.2 (± 3.0) in the combined reference group.

A total of 10 patients in the CT-P10 group (52.5%), 4 patients in the US reference group (30.8%), and 3 patients in the EU reference group (42.9%) tested positive for antidrug antibodies (ADAs) at 1 or more time points up to week 48. Three patients (15.8%), 2 patients (15.4%), and 0 patients (0.0%), respectively, tested positive for ADAs at week 48, and neutralizing antibodies were detected in 2 patients, 1 in the CT-P10 group and 1 in the US reference group.

In total, 70.2% of all patients reported an adverse event (AE) by week 48, and AEs occurred in a similar proportion among groups. Most AEs were grade 1 or 2, and the most common was upper respiratory infection, followed by infusion-related reactions. A total of 34 serious AEs were reported. Similar proportions of patients in each group experienced AEs leading to discontinuation. At week 48, no cases of progressive multifocal leukoencephalopathy or hepatitis B reactivation had been reported. Four malignancies, all in the reference groups, were reported.

The authors concluded that this study demonstrated the long-term similarity of CT-P10 and its EU and US references and further supports the approval of the biosimilar to treat RA and related diseases.

Reference

Suh CH, Yoo DH, Kasay AB, et al. Long-term efficacy and safety of biosimilar CT-P10 versus innovator rituximab in rheumatoid arthritis: 48-week results from a randomized phase 3 trial [published online February 5, 2019]. BioDrugs. doi: 10.1007/s40259-018-00331-4.