SAT0152 A Randomised, Double-Blind, Phase III Study Comparing SB2, An Infliximab Biosimilar, To the Infliximab Reference Product (Remicade®) in Patients with Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy

Background SB2 is developed as a biosimilar of the infliximab reference product (INF). Objectives This is a phase III equivalence study to compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to INF in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods Patients with moderate to severe RA despite MTX therapy were randomised in a 1:1 ratio to receive either SB2 or INF (3 mg/kg). Dosing occurred at week 0, 2, 6 and then every 8 weeks until week 46. The primary endpoint was the ACR20 response rate at week 30. Other secondary efficacy, safety, immunogenicity and PK endpoints were also measured. Results A total of 584 patients were randomised to either SB2 (N=291) or INF (N=293). Baseline demographic and disease characteristics were comparable between two treatment groups. The ACR20 response rate at week 30 in the per-protocol set (PPS) was 64.6% (148/229) in SB2 vs. 66.0% (159/241) in INF. The rate difference adjusted by region and baseline C-reactive protein was −1.67% (95% confidence interval [95% CI], −10.13% to 6.78%), which was within the pre-defined equivalence margin of [−15%, 15%]. The ACR50 response rates at week 30 in the PPS were 35.8% vs. 37.8% and the ACR70 response rates were 18.3% vs. 19.1% in SB2 and INF, respectively. The ACR20 response rate at week 30 in the full analysis set (FAS) was also within the equivalence margin (55.5% vs. 59.0%; rate difference, −2.95%; 95% CI, −10.88% to 4.97%) when non-responder analysis was applied. The time-response curve for ACR20 response in the PPS was estimated to be equivalent between SB2 and INF (Figure). The safety profile was comparable between two treatment groups (Table). The overall anti-drug antibody positivity up to week 30 was 55.1% in SB2 vs. 49.7% in INF. PK profiles were also comparable between the two treatment groups of the PK study population. Table 1. Safety profile of the study population Number of patients with SB2 (N=290)* INF (N=293) n % n % At least 1 TEAE 167 57.6 170 58.0 At least 1 SAE 26 9.0 26 8.9 Total infections 74 25.5 92 31.4 Tuberculosis 1 0.3 1 0.3 Infusion-related reaction 15 5.2 13 4.4 Malignancy 2 0.7 0 0.0 Death 0 0 1 0.3 SAE: serious adverse event; TEAE: treatment-emergent adverse event.* 1 subject dropped out before receiving at least 1 dose of SB2. Conclusions SB2 was shown to be equivalent to INF in terms of ACR20 response rate up to week 30. SB2 was well tolerated with a comparable safety profile, PK and immunogenicity. Disclosure of Interest J.-Y. Choe Grant/research support from: Samsung Bioepis, Consultant for: Samsung Bioepis, N. Prodanovic Grant/research support from: Samsung Bioepis, J. Niebrzydowski Grant/research support from: Samsung Bioepis, I. Staykov Grant/research support from: Samsung Bioepis, E. Dokoupilova Grant/research support from: Samsung Bioepis, A. Baranauskaite Grant/research support from: AbbVie, Samsung Bioepis, R. Yatsyshyn Grant/research support from: Samsung Bioepis, M. Mekic Grant/research support from: Samsung Bioepis, W. Porawska Grant/research support from: Samsung Bioepis, H. Ciferska Grant/research support from: Samsung Bioepis, K. Jedrychowicz-Rosiak Grant/research support from: Samsung Bioepis, A. Zielinska Grant/research support from: Samsung Bioepis, J. Y. Bang Employee of: Samsung Bioepis, Y. H. Rho Employee of: Samsung Bioepis, J. S. Smolen Grant/research support from: AbbVie, Jassen, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Celgene, GSK, Jassen, Lilly, Medimmune, MSD, Norvartis-Sandoz, Novo Nordisk, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB