SAT0132\u2005LONG-TERM SAFETY, IMMUNOGENICITY AND EFFICACY IN RANDOMIZED, DOUBLE-BLIND, AND OPEN-LABEL EXTENSION STUDIES COMPARING FKB327, AN ADALIMUMAB BIOSIMILAR, WITH THE ADALIMUMAB REFERENCE PRODUCT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

Abstract

Background FKB327 is a biosimilar of adalimumab reference product (RP). Studies with adalimumab biosimilars have shown no increase in safety signals or immunogenicity versus RPs studied at 52 weeks. Objectives To study the long-term safety, immunogenicity and efficacy of FKB327 compared with Adalimumab RP in a randomized double blind (DB) phase 3 study in patients (pts) with active rheumatoid arthritis (RA) inadequately controlled with methotrexate (MTX) and in a subsequent randomized, open-label extension (OLE) study with treatment switching assessed long-term safety, efficacy, PK, and immunogenicity. Methods Pts aged ≥18 years with moderate-to-severe, active RA (2010 ACR/EULAR criteria) for ≥3 months and receiving a stable dose of MTX were randomized 1:1 to FKB327 or RP (40 mg subcutaneously [SQ]) every other week with MTX. In the OLE study, pts who completed the DB study with clinical response and no serious adverse events (AEs) were rerandomized in a 2:1 ratio to FKB327 or RP. All pts received FKB327 through week 76 (Period 2). The primary end point was safety; the secondary end point was efficacy. Pooled data for up to 2 years were analyzed to assess long-term safety. Incidence rates of treatment-emergent AEs were adjusted by overall exposure to enable safety comparison of FKB327 and RP. Results Of 728 pts in the DB study, 645 were enrolled in the OLE; of those, 572 and 515 pts completed periods 1 and 2, respectively. Safety results from the pooled data were comparable between treatment sequences. Mean serum drug concentrations appeared to be in steady–state in all treatment sequences in Period 1 and comparable among sequences in Period 2. The proportion of pts with positive antidrug antibody (ADA) status in Period 1 was comparable between treatment sequences, and the majority of patients with positive ADA status had neutralizing activity. The mean proportion of patients achieving an ACR20 response remained stable between studies and was similar for all treatment sequences.Table. Summary of Efficacy & Safety End Points at Week 30 (Period 2): Full Analysis Set F-F-F N = 216 F-H-F N = 108 H-F-F N = 108 H-H-F N= 213 ACR20 response rate n 185 98 92 189 Responders, n (%) 154 (83.2) 82 (83.7) 79 (85.9) 158 (83.6) 95% CI 77.1-88.3 74.8-90.4 77.0-92.3 77.5, 88.6 ACR50 response rate n 185 98 92 189 Responders (%) 112 (60.5) 57 (58.2) 50 (54.3) 113 (59.8) 95% CI 53.1-67.6 47.8-68.1 43.6-64.8 52.4, 66.8 DAS28-CRP response rate n 183 99 92 189 Mean (SD) 3.04 (1.237) 3.28 (1.385) 3.20 (1.247) 3.13 (1.239) Range 1.2-7.1 1.2-7.1 1.3-6.3 1.2, 7.4 ADA status Total 187 100 93 190 Positive 97 (51.9) 61 (61.0) 42 (45.2) 98 (51.6) ACR indicates American College of Rheumatology; ADA, antidrug antibody; CI, confidence interval; DAS28, Disease Activity Score-28 with C-reactive protein; F, FKB327; H, adalimumab; SD, standard deviation. Conclusion The safety, immunogenicity, and efficacy of FKB327 were maintained over long-term treatment and after switching between the biosimilar and RP. Disclosure of Interests Rieke Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Yasumasa Arai Employee of: I am an employee of Fujifilm Kyowa Kirin Biologics., Rafael Muniz Shareholder of: Employee of Mylan, Consultant for: Employee of Mylan, Employee of: Employee of Mylan, Herbert Kellner Grant/research support from: Roche, Consultant for: Roche