Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks

Chang-Hee Suh¹, Alfredo Berrocal Kasay², Elias Chalouhi El-Khouri³, Pedro Miranda⁴, Ljubinka Bozic Majstorovic⁵, Slawomir Jeka⁶, Pawel Hrycaj⁷, Dmytro Rekalov⁸, Piotr Wiland⁹, Andreas Krause¹⁰, Istvan Szombati¹¹, Anna Mihailova¹², Ihor Hospodarskyy¹³, Mariusz Piotrowski¹⁴, Seong-Ryul Kwon¹⁵, Eun-Young Lee¹⁶, Dae-Hyun Yoo¹⁷, Won Park¹⁸, Seung-Cheol Shim¹⁹, Sang-Joon Lee²⁰ and Taek S. Kwon²⁰, ¹Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea, The Republic of, ²ABK Reuma SRL – Medicentro Biociencias, Lima, Peru, ³Clinica Internacional, Lima, Peru, ⁴Centro De Estudios Reumatológicos, Santiago, Chile, ⁵Clinical Centre Banja Luka, Bonja Luka, Bosnia and Herzegovina, ⁶Department of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK, Bydgoszcz, Poland, ⁷Rheumatology and Clinical Immunology, Poznañ University of Medical Sciences, Poznan, Poland, ⁸Department of Internal Diseases, Zaporizhzhia Regional Hospital, Zaporozhe, Ukraine, ⁹Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckigo, Wroclaw, Poland, ¹⁰Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin, Germany, ¹¹QUALICLINIC Kft., Budapest, Hungary, ¹²Orto clinic Ltd., Riga, Latvia, ¹³Ternopil State Medical University, Ternopil, Ukraine, ¹⁴Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Poland, Lublin, Poland, ¹⁵Internal Medicine/Rheumatology, Inha University Hospital, Incheon, South Korea, ¹⁶Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, The Republic of, ¹⁷Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ¹⁸Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea, ¹⁹Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea, ²⁰CELLTRION, Inc., Incheon, South Korea

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biologics, biosimilars, monoclonal antibodies, rheumatoid arthritis (RA) and rituximab

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Result from Phase 3 Randomized Controlled Trial over 24 Weeks

Background/Purpose : CT-P10 is a proposed biosimilar candidate of rituximab, and it has been concluded to be highly similar to the reference product in terms of analytical and functional characteristics and equivalent to EU-sourced innovator rituximab (EU-RTX) in pharmacokinetics (PK) in the patients with RA through phase 1 study.¹ The similarity in terms of PK was tested among CT-P10 and two innovator rituximabs from the different manufacturing sources in RA patients.

Methods : A total of 189 RA patients in PK analysis part from a randomized controlled phase 3 study (NCT02149121) was randomly assigned in 1:1:1 ratio to receive 2 infusions of 1,000 mg CT-P10, US-sourced innovator rituximab (US-RTX) or EU-RTX with a 2-week interval. The following PK parameters were coprimary endpoints: area under the serum concentration-time curve from time zero to the last measurable concentration (AUC_0-last), AUC from time zero extrapolated to infinity (AUC_0-_inf) and maximum concentration after the second infusion (C_max) of CT-P10, US-RTX or EU-RTX. Pharmacokinetic similarity is concluded if the 90% confidence interval (CI) for the ratio of geometric means in AUC_0-last, AUC_0-inf, and C_max are entirely contained within the bounds of 80% and 125% for the following comparisons: CT-P10 vs US-RTX, CT-P10 vs EU-RTX, and US‑RTX vs EU-RTX.

Results : The PK parameters among 3 treatment groups were highly similar (Table 1). The 90% CIs for the ratio of geometric means for coprimary endpoints fell within the PK equivalence margin of 80-125% indicating that drug exposures from CT-P10 are similar to those from both US-RTX and EU-RTX and also from US-RTX to those of EU-RTX (Table 2). The safety profiles among 3 treatment groups were generally similar. Adverse events (AEs) due to infusion related reaction were reported for 6 (9.4%), 4 (6.2%) and 12 (20.0%) patients in CT‑P10, US-RTX and EU-RTX, respectively. All these events were mild to moderate (grade 1 or 2) in intensity. Six patients were discontinued due to an AE (2 [3.1%], 3 [4.6%] and 1 [1.7%] patients in CT-P10, US-RTX and EU-RTX, respectively). No malignancy, progressive multifocal leukoencephalopathy, serious infection or death occurred in any of the treatment groups.

Conclusion : Pharmacokinetic equivalence was demonstrated in terms of AUC_0-last, AUC_0-_inf andC_max in the comparisons of CT-P10 to US-RTX, CT-P10 to EU-RTX, and US-RTX to EU-RTX in RA patients. In addition, comparable safety profiles were observed among the 3 treatment groups. Reference 1. Yoo DH, et al. Arthritis Rheum 2013;65(Suppl 10): S736

Disclosure: C. H. Suh, CELLTRION,Inc., 5; A. Berrocal Kasay, CELLTRION,Inc., 2; E. Chalouhi El-Khouri, CELLTRION,Inc., 2; P. Miranda, CELLTRION,Inc., 2; L. Bozic Majstorovic, CELLTRION,Inc., 2; S. Jeka, CELLTRION,Inc., 2; P. Hrycaj, CELLTRION,Inc., 2; D. Rekalov, CELLTRION,Inc., 2; P. Wiland, CELLTRION,Inc., 2; A. Krause, CELLTRION,Inc., 2; I. Szombati, CELLTRION,Inc., 2; A. Mihailova, CELLTRION,Inc., 2; I. Hospodarskyy, CELLTRION,Inc., 2; M. Piotrowski, CELLTRION,Inc., 2; S. R. Kwon, CELLTRION,Inc., 2; E. Y. Lee, CELLTRION,Inc., 2; D. H. Yoo, CELLTRION,Inc., 5; W. Park, CELLTRION,Inc., 5; S. C. Shim, CELLTRION,Inc., 5; S. J. Lee, CELLTRION,Inc., 3; T. S. Kwon, CELLTRION,Inc., 3.

To cite this abstract in AMA style:

Suh CH, Berrocal Kasay A, Chalouhi El-Khouri E, Miranda P, Bozic Majstorovic L, Jeka S, Hrycaj P, Rekalov D, Wiland P, Krause A, Szombati I, Mihailova A, Hospodarskyy I, Piotrowski M, Kwon SR, Lee EY, Yoo DH, Park W, Shim SC, Lee SJ, Kwon TS. Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pharmacokinetics-and-safety-of-three-formulations-of-rituximab-ct-p10-us-sourced-innovator-rituximab-and-eu-sourced-innovator-rituximab-in-patients-with-rheumatoid-arthritis-results-from-phase-3-r/. Accessed .

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