Session Information
Date: Monday, October 22, 2018
Title: 4M106 ACR Abstract: RA–Treatments III: New Compounds & Biosimilars (1935–1940)
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: GP2017, a proposed adalimumab biosimilar, matched reference adalimumab (refADL) in preclinical and pharmacokinetics studies.1,2 The confirmatory efficacy and safety study in patients with plaque-type psoriasis demonstrated equivalent efficacy and similar safety of GP2017 and refADL.3
This Phase III study compares efficacy and safety of GP2017 and refADL in patients with moderate-to-severe rheumatoid arthritis (RA) with inadequate response to disease modifying anti-rheumatic drugs, including methotrexate (NCT02744755). The study was designed to demonstrate similar efficacy of GP2017 and refADL over 24 weeks of treatment, and to evaluate long-term safety, immunogenicity and efficacy of GP2017 up to Week (Wk) 48. Data from randomization to Wk 24 are presented.
Methods:
Eligible patients were randomized 1:1 to receive 40 mg subcutaneous GP2017 or refADL every other week from Wk 0 to Wk 22. The primary endpoint was change in Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) from baseline at Wk 12. Therapeutic equivalence was confirmed if the 95% confidence intervals (CIs) for the difference in DAS28-CRP change from baseline (BL) at Wk 12 between GP2017 and refADL were completely contained within the predefined equivalence margin of [-0.6,0.6]. Secondary endpoints included time-weighted averaged change in DAS28-CRP from BL to Wk 24, safety and immunogenicity.
Results:
In total, 353 patients were randomized to receive GP2017 (n=177) or refADL (n=176). Using a mixed model repeated measures method, mean change from BL at Wk 12 in DAS28-CRP was -2.16 for GP2017 (n=140) and -2.18 for refADL (n=144) (∆=0.02; 95% CI: -0.24,0.27). Time-weighted averaged change from BL in DAS28-CRP until Wk 24 was -1.85 for GP2017 (n=127) and -1.93 for refADL (n=138) (∆=0.08; 95% CI: -0.11,0.27). Treatment-emergent adverse events (TEAEs) occurred in 61.6% of patients in GP2017 group and 60.2% of patients in refADL group (Table). Most TEAEs were mild or moderate in severity. Infections and infestations were most common TEAEs, of those mild viral upper respiratory tract infections were reported by 14.7% and 9.1% of patients in GP2017 and refADL groups, respectively. Injection site reactions occurred in 7 (4.0%) and 11 (6.3%) patients in GP2017 and refADL groups. From BL to Wk 24, antidrug antibodies were detected in 21.8% and 24.4% of patients treated with GP2017 and refADL, of which >70% in both groups were neutralizing.
Conclusion:
These data demonstrate equivalent efficacy of proposed adalimumab biosimilar GP2017 and refADL in patients with moderate-to-severe RA. Safety and immunogenicity of GP2017 and refADL were similar and consistent with clinical experience with refADL.
References
1da Silva A, et al. Am J Gastroenterol 2016;111:S284
2Jauch-Lembach J, et al. Arthritis Rheumatol 2017;69 (suppl 10)
3Blauvelt A, et al. Arthritis Rheumatol 2017;69 (suppl 10)
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Table. Summary of safety and immunogenicity for the proposed biosimilar adalimumab, GP2017, and reference adalimumab from baseline to Week 24 (analysis set) |
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GP2017 |
Reference adalimumab (refADL) (n=176) |
Total |
|
|
Adverse events, n (%) |
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|
≥1 TEAE |
109 (61.6) |
106 (60.2) |
215 (60.9) |
|
Most commonly affected SOC |
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|
Infections and infestations |
63 (35.6) |
65 (36.9) |
128 (36.3) |
|
Gastrointestinal disorders |
21 (11.9) |
17 (9.7) |
38 (10.8) |
|
Musculoskeletal and connective tissue disorders |
21 (11.9) |
14 (8.0) |
35 (9.9) |
|
≥1 treatment-related TEAE |
42 (23.7) |
32 (18.2) |
74 (21.0) |
|
≥1 severe TEAE |
3 (1.7) |
3 (1.7) |
6 (1.7) |
|
≥1 SAE |
5 (2.8) |
4 (2.3) |
9 (2.5) |
|
Injection site reaction |
7 (4.0) |
11 (6.3) |
18 (5.1) |
|
Drug discontinuation due to TEAE |
2 (1.1) |
2 (1.1) |
4 (1.1) |
|
Death |
0 |
0 |
0 |
|
Incidence of ADAs from baseline to Week 24, n/n (%) |
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Positive |
36/165 (21.8) |
41/168 (24.4) |
77/333 (23.1) |
|
Neutralizing |
27/36 (75.0) |
30/41 (73.2) |
57/77 (74.0) |
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ADAs, antidrug antibodies; AE, adverse event; SAE, serious adverse event; SOC, system organ class; TEAE, treatment-emergent adverse event |
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To cite this abstract in AMA style:
Wiland P, Jeka S, Dokoupilová E, Miranda Limón JM, Jauch-Lembach J, Thakur A, Haliduola H, Gaylis NB. A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Efficacy, Safety and Immunogenicity of a Proposed Adalimumab Biosimilar (GP2017) with Reference Adalimumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/a-randomized-double-blind-parallel-group-multicenter-study-to-compare-the-efficacy-safety-and-immunogenicity-of-a-proposed-adalimumab-biosimilar-gp2017-with-reference-adalimumab-in-patients-with/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-parallel-group-multicenter-study-to-compare-the-efficacy-safety-and-immunogenicity-of-a-proposed-adalimumab-biosimilar-gp2017-with-reference-adalimumab-in-patients-with/