ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0800

A Randomized, Double-Blind, Phase 3 Study to Compare the Efficacy and Safety of a Proposed High Concentration (100 mg/mL) Adalimumab Biosimilar (CT-P17) with Reference Adalimumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis

Jonathan Kay1, Janusz Jaworski2, Rafal Wojciechowski3, Piotr Wiland4, Anna Dudek5, Marek Krogulec6, Slawomir Jeka7, Agnieszka Zielinska8, Jakub Trefler9, Katarzyna Bartnicka-Maslowska10, Magdalena Krajewska-Wlodarczyk11, Piotr Klimiuk12, Daniel Furst*13, SangJoon Lee14, YunJu Bae14, GoEun Yang14, JaeKyoung Yoo14, HyunJin Lee14 and Edward C Keystone15, 1University of Massachusetts Medical School, Worcester, MA, 2Reumatika-Centrum Reumatologii, Warsaw, Poland, 3University Hospital No 2, Bydgoszcz, Poland, 4Medical Univeristy, Wroclaw, Poland, 5Centrum Medyczne AMED, Warsaw, Poland, 6Rheumatology Clinic NZOZ Lecznica MAK-MED, Nadarzyn, Poland, 72nd Univ Hospital, CM UMK, Bydgoszcz, Poland, 8Medycyna Kliniczna Marzena Waszczak-Jeka, Warsaw, Poland, 9Reuma Centrum, Warsaw, Poland, 10Centrum Medyczne AMED oddzial w Łodzi, Łódź, Poland, 11University of Warmia and Mazury, Olsztyn, Poland, 12Medical University of Białystok and Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk, Białystok, Poland, 13Department of Medicine, Division of Rheumatology, University of California at Los Angeles, Los Angeles, California, USA, Los Angeles, CA, 14Celltrion, Inc., Incheon, Republic of Korea, 15Mount Sinai Hospital, Toronto, ON, Canada

Meeting: ACR Convergence 2020

Keywords: , , , ,

Session Information

Date: Saturday, November 7, 2020

Session Title: RA – Treatments Poster II: Comparative Effectiveness, Biosimilars, Adherence & the Real World

Session Type: Poster Session B

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

Background/Purpose: CT-P17 (100 mg/mL) is the first proposed biosimilar of the high concentration and citrate-free formulation of reference adalimumab. The purpose of this study was to compare the efficacy and safety of CT-P17 with reference adalimumab in patients with active moderate-to-severe RA up to Week 52.

Methods: Patients with active moderate-to-severe RA despite methotrexate treatment were randomly assigned to receive 40 mg of CT-P17 or reference adalimumab every 2 weeks up to Week 24. Prior to dosing at Week 26, patients in the reference adalimumab group were re-randomized either to continue receiving reference adalimumab or to switch to CT-P17 until end of study. All patients initially randomized to CT-P17 continued CT-P17. The primary endpoint was ACR20 response rate at Week 24. Secondary measures of efficacy, pharmacokinetics (PK) and safety, including immunogenicity, were also evaluated.

Results: 648 patients initiated treatment (324 patients in each arm). Baseline characteristics were similar between groups.

The ACR20 response rate at Week 24 was 82.7% (268/324) and 82.7% (268/324) for CT-P17 and reference adalimumab and the confidence intervals of the treatment difference (95% CI: -5.94 to 5.94, 90% CI: -4.98 to 4.98) were entirely within the equivalence margins agreed upon with EMA (±15%) and FDA (-12% to +15%). Secondary efficacy endpoints were also similar between groups (Table 1).

In terms of PK, geometric mean trough serum concentration was slightly higher in CT-P17; 5.3 μg/mL in CT-P17 vs. 4.3 μg/mL in reference adalimumab at Week 24 (p=0.0501).

Overall, 353 (CT-P17: 169 [52.2%] vs. reference adalimumab: 184 [56.8%]) patients experienced at least 1 treatment-emergent adverse event (TEAE). The most common TEAEs were injection site reactions (16 [4.9%] vs. 22 [6.8%]). 26 patients experienced at least 1 treatment-emergent serious adverse event (TESAE). Similar proportions of patients in both groups experienced at least 1 TEAE that was classified as hypersensitivity/allergic reactions and infections (Table 2). One malignancy (breast cancer; unrelated) was reported in a patient receiving CT-P17.

The proportion of patients who had anti-drug antibodies (ADAs) at Week 24 (209 [32.3%]), was slightly lower for CT-P17 (93 [28.7%]) than for reference adalimumab (116 [35.8%]) (p=0.0643). Of these, 83 (25.6%) receiving CT-P17 and 103 (31.8%) receiving reference adalimumab also had neutralizing ADAs.

Conclusion: Over 24 weeks, CT-P17 has equivalent efficacy to reference adalimumab, with ACR20 response rates of 82.7% for each, and similar additional secondary efficacy endpoints. Considering the ACR20 response rate of 64.0% – 82.5% [1-4] reported in previous studies of low concentration (50 mg/mL) adalimumab biosimilar, further investigation is needed to ascertain the factors associated with the slightly higher response rate in this study.

CT-P17 was well tolerated with a safety profile comparable to that of reference adalimumab.

References:

  1. Cohen SB et al. Ann Rheum Dis. 2017 Oct; 76(10):1679-1687
  2. Cohen SB et al. Ann Rheum Dis.2018 Jun; 77(6):914-921
  3. Weinblatt ME, Arthritis Rheumatol. 2018 Jan; 70(1):40-48
  4. US FDA, Multi-disciplinary Evaluation and Review for PF-06410293, 2019

Disclosure: J. Kay, Pfizer Inc., 9, Alvotech Suisse AG, 1, Arena Pharmaceuticals, Inc., 1, Boehringer Ingelheim GmbH, 1, Celltrion Healthcare Co. Ltd., 1, Mylan Inc., 5, Novartis AG, 5, Samsung Bioepis, 5, Sandoz Inc., 5, Gilead Sciences, Inc., 9; J. Jaworski, None; R. Wojciechowski, None; P. Wiland, Celltrion, Inc., 1, Novartis, Pfizer, Abbvie, Gedeon-Richter, Lilly, Roche, Sandoz, 1; A. Dudek, None; M. Krogulec, Celltrion, 1; S. Jeka, Pfizer, 2, 8, Novartis, 2, 8, Abbvie, 2, 8, UCB, 2, 8, MSD, 2, 8, Roche, 2, 8, Sandoz, 2, 8, Egis, 2, 8, Lilly, 2, 8, Celgene, 2, 8; A. Zielinska, None; J. Trefler, None; K. Bartnicka-Maslowska, None; M. Krajewska-Wlodarczyk, None; P. Klimiuk, None; D. Furst*, Actelion, 1, 2, Amgen, 1, 2, BMS, 1, Corbus, 1, 2, Galapagos, 1, 2, GSK, 1, NIH, 1, Norvatis, 1, 2, Pfizer, 1, 2, Sanofi, 1, Roche/Genentech, 1, Gilead, 1, Horizon, 1, 2, Kadmon, 1, Talaris, 1, 2, CMC Connect (McCann Health Company), 8, Cytori, 5, AbbVie, 5; S. Lee, Celltrion, Inc., 1; Y. Bae, CELLTRION, Inc., 1; G. Yang, Celltrion, Inc., 1; J. Yoo, Celltrion, INC., 1; H. Lee, Celltrion, Inc., 1; E. Keystone, AbbVie, 2, 5, 8, Celltrion, 2, 5, 8, Eli Lilly, 2, 5, 8, Pfizer Inc, 2, 5, 8, Merck, 2, 5, 8, Sandoz, 2, 5, 8, Samsung Bioepsis, 2, 5, 8, Myriad Autoimmune, 2, 5, 8, Purapharm, 2, 5, 8, Janssen, 2, 5, 8, Sanofi-Genzyme, 2, 5, 8, Amgen, 2, 5, 8, AstraZeneca, 2, 5, 8, Bristol-Myers Squibb, 2, 5, 8, F. Hoffman-La Roche Ltd., 2, 5, 8, Genentech, 2, 5, 8, Gilead, 2, 5, 8, UCB, 2, 5, 8.

To cite this abstract in AMA style:

Kay J, Jaworski J, Wojciechowski R, Wiland P, Dudek A, Krogulec M, Jeka S, Zielinska A, Trefler J, Bartnicka-Maslowska K, Krajewska-Wlodarczyk M, Klimiuk P, Furst* D, Lee S, Bae Y, Yang G, Yoo J, Lee H, Keystone E. A Randomized, Double-Blind, Phase 3 Study to Compare the Efficacy and Safety of a Proposed High Concentration (100 mg/mL) Adalimumab Biosimilar (CT-P17) with Reference Adalimumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/a-randomized-double-blind-phase-3-study-to-compare-the-efficacy-and-safety-of-a-proposed-high-concentration-100-mg-ml-adalimumab-biosimilar-ct-p17-with-reference-adalimumab-in-patients-with-mode/. Accessed April 11, 2021.

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