Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks

Dae-Hyun Yoo¹, Won Park², Chang-Hee Suh³, Seung-Cheol Shim⁴, Slawomir Jeka⁵, Fidencio Cons Molina⁶, Pawel Hrycaj⁷, Wolfgang Spieler⁸, Piotr Wiland⁹, Jan Brzezicki¹⁰, Eun Young Lee¹¹, Francisco G. Medina-Rodriguez¹², Pavel Shesternya¹³, Sebastiao Radominski¹⁴, Marina Stanislav¹⁵, Volodymyr Kovalenko¹⁶, Donghyuk Sheen¹⁷, Leysan Myasoutova¹⁸, Mie Jin Lim¹⁹, Jung-Yoon Choe²⁰, Taek S. Kwon²¹ and Sang Joon Lee²¹, ¹Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea, ³Department of Rheumatology, Ajou University Hospital, Suwon, South Korea, ⁴Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea, ⁵University Hospital Nr 2 Dr. Jan Biziel, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Clinic of Rheumatology and Connective Tissue Diseases, Bydgoszcz, Poland, ⁶Centro de Investigacion en Artritis y Osteoporosis, Mexicali, Mexico, ⁷Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland, ⁸Osteologie und Rheumatologie, ZeFOR GmbH Zentrum für Forschung, Zerbst, Germany, ⁹Department of Rheumatology, Medical University of Wroclaw, Wroclaw, Poland, ¹⁰Wojewodzki Szpital Zespolony w Elablagu, Elblag, Poland, ¹¹Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, ¹²Rheumatology, LaSalle University, Mexico City, Mexico, ¹³Rheumatology Department, Krasnoyarsk State Medical University, Krasnoyarsk, Russia, ¹⁴CETI-Centro de estudos em Terapias Inovadoras, Universidade Federal do Parana, Curitiba, Brazil, ¹⁵Research Rheumatology Institute n. a. V.A. Nassonova, Moscow, Russia, ¹⁶Section of Non-coronarogenic Myocardial Diseases and Clinical Rheumatology, National Scientific Center, Kiev, Ukraine, ¹⁷Rheumatology, Eulji University Hospital, Daejeon, South Korea, ¹⁸City Reumatology Center, Research Medical Complex Vashe Zdorovie, Kazan, Russia, ¹⁹Division of Rheumatology, Departments of Internal Medicine, Inha University Hospital, Incheion, South Korea, ²⁰Internal Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea, ²¹CELLTRION, Inc., Incheon, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

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

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy III: Biosimilars

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: CT-P10
is a biosimilar candidate of innovator rituximab (RTX). PK profile and clinical
data up to week 24 has been reported at ACR 2013¹. Additional safety
and efficacy were evaluated to confirm similarity between CT-P10 and RTX up to 72
weeks (NCT01534884).

Methods: Patients
with active RA (1987 ACR criteria) and intolerant or unresponsive to anti TNF-a
blocker were randomized 2:1 to receive 2 infusions (1,000 mg, IV each) of
either CT-P10 or RTX, at a 2-week interval, in combination with methotrexate
(MTX) and folic acid. The second course of treatment was initiated between
weeks 24 ~ 48 based on disease activity and predefined safety criteria. The end
of study visit for patients who did not receive the second course of treatment
was conducted at week 48 (Figure 1). Efficacy was analyzed in per-protocol
population.

Results: Of
154 patients randomized at baseline, 132 (85.7%) patients completed the study. The
efficacy in terms of DAS28 changes and overall safety were comparable between CT-P10
and RTX treatment groups. The mean decreases from baseline in DAS28 at Week 24
after 1^st and 2^nd courses of treatment were similar between
CT-P10 and RTX treatment groups (Table 1). The proportion of patients experienced
at least one adverse event (AE), serious AE, infusion related reaction,
infection, malignancy or lymphoma and discontinuation due to AE was similar
between CT-P10 and RTX treatment groups (Table 2). Cervix carcinoma stage 0 was
reported in a patient from RTX group, and no deaths were reported. B-cell
kinetics between the CT‑P10 and RTX treatment groups were similar at all time
points. The mean changes from baseline in IgM, IgG, and IgA were small, and
there were no notable differences between the CT-P10 and RTX treatment groups.

Table
1
Efficacy of CT-P10 and Innovator Rituximab by DAS28 Changes

	CT-P10	RTX
DAS28-CRP, Mean ± SD (n)
Baseline	6.0 ± 0.9 (100)	6.0 ± 0.8 (47)
Changes at Week 24 after 1^st Course	̶ 1.9 ± 1.2 (95)	̶ 2.0 ± 1.5 (43)
Changes at Week 24 after 2^nd Course	̶ 2.4 ± 1.3 (58)	̶ 2.0 ± 1.2 (20)
DAS28-ESR, Mean ± SD (n)
Baseline	6.8 ± 0.8 (100)	6.7 ± 0.8 (47)
Changes at Week 24 after 1^st Course	̶ 2.1 ± 1.2 (95)	̶ 2.1 ± 1.5 (43)
Changes at Week 24 after 2^nd Course	̶ 2.5 ± 1.3 (58)	̶ 2.0 ± 1.2 (20)
RTX, innovator rituximab; DAS28, disease activity score in 28 joints; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SD, standard deviation

Table 2
Safety Summary of CT-P10 and Innovator Rituximab

	CT-P10 N=102	RTX N=51
Number of Patients (%) with at Least One
AE	73 (71.6)	43 (84.3)
Serious AE	14 (13.7)	7 (13.7)
Infusion-related reaction	20 (19.6)	10 (19.6)
Infection	39 (38.2)	21 (41.2)
Malignancy	0	1 (2.0)
Discontinuation due to AEs	6 (5.9)	4 (7.8)

RTX, innovator rituximab; AE, adverse events

Conclusion: CT-P10,
a biosimilar candidate of RTX, showed highly similar efficacy and comparable safety
profiles to RTX up to 72 weeks.

Reference

¹Yoo DH, et al.
Arthritis Rheum 2013; 65 (Suppl 10): S736

Disclosure: D. H. Yoo, CELLTRION, Inc., 5; W. Park, CELLTRION, Inc., 5; C. H. Suh, CELLTRION, Inc., 5; S. C. Shim, CELLTRION, Inc., 5; S. Jeka, CELLTRION, Inc., 2; F. Cons Molina, CELLTRION, Inc., 2; P. Hrycaj, CELLTRION, Inc., 2; W. Spieler, CELLTRION, Inc., 2; P. Wiland, CELLTRION, Inc., 2; J. Brzezicki, CELLTRION, Inc., 2; E. Y. Lee, CELLTRION, Inc., 2; F. G. Medina-Rodriguez, CELLTRION, Inc., 2; P. Shesternya, CELLTRION, Inc., 2; S. Radominski, CELLTRION, Inc., 2; M. Stanislav, CELLTRION, Inc., 2; V. Kovalenko, CELLTRION, Inc., 2; D. Sheen, CELLTRION, Inc., 2; L. Myasoutova, CELLTRION, Inc., 2; M. J. Lim, CELLTRION, Inc., 2; J. Y. Choe, CELLTRION, Inc., 2; T. S. Kwon, CELLTRION, Inc., 3; S. J. Lee, CELLTRION, Inc., 3.

To cite this abstract in AMA style:

Yoo DH, Park W, Suh CH, Shim SC, Jeka S, Cons Molina F, Hrycaj P, Spieler W, Wiland P, Brzezicki J, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, Kovalenko V, Sheen D, Myasoutova L, Lim MJ, Choe JY, Kwon TS, Lee SJ. Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-rituximab-biosimilar-candidate-ct-p10-and-innovator-rituximab-in-patients-with-rheumatoid-arthritis-results-from-phase-i-randomized-controlled-trial-over-72-weeks/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-rituximab-biosimilar-candidate-ct-p10-and-innovator-rituximab-in-patients-with-rheumatoid-arthritis-results-from-phase-i-randomized-controlled-trial-over-72-weeks/