A Phase III, Randomized, Double-Blind Clinical Study Comparing SB5, an Adalimumab Biosimilar, with Adalimumab Reference Product (Humira®) in Patients with Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy (24-week Results)

BACKGROUND/PURPOSE: SB5 is a biologic agent developed as a biosimilar of the adalimumab reference product (ADL). Equivalence in pharmacokinetics (PK) between SB5 and ADL in healthy subjects has been demonstrated1 in a phase I study. This phase III study was a randomized, double-blind, multicenter study to compare the efficacy, safety, PK, and immunogenicity of SB5 with ADL in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) treatment up to 52 weeks. Results up to 24 weeks are presented in this abstract. METHODS: Patients with moderate to severe RA despite MTX treatment were randomly assigned to receive 40 mg of either SB5 or ADL administered subcutaneously every other week for 24 weeks. At Week 24, patients in ADL group were randomized again to receive 40 mg of either SB5 or ADL for additional 28 weeks. Patients in SB5 group continued to receive SB5. The primary endpoint was the ACR20 response rate at Week 24. Other secondary efficacy endpoints and safety were measured. RESULTS: A total of 544 patients were randomized to either SB5 (N=271) or ADL (N=273). Baseline demographic and disease characteristic were comparable between two treatment groups. The ACR20 response rate at Week 24 in the per-protocol set (PPS) was 72.5% (174/240) in SB5 and 72.0% (170/236) in ADL. The 95% confidence interval (CI) of the treatment difference adjusted by region and baseline C-reactive protein was –7.66% to 8.30%, which was within the pre-defined equivalence margin of [–15%, 15%]. The ACR20 response rate at Week 24 was shown to be equivalent in the full analysis set as well (95% CI: -7.03%, 8.56%) when non-responder analysis was applied. The 95% CI of the estimated difference between the time-response curves of SB5 and ADL in the PPS met the pre-defined equivalence margin (Figure). The ACR50 response rates at Week 24 in the PPS were 38.3% vs. 39.8% and the ACR70 response rates were 19.2% vs. 20.3% in SB5 and ADL, respectively. The safety profile of SB5 was generally similar to that of ADL (Table). The overall incidence of anti-drug antibody up to Week 24 was 32.8% in SB5 vs. 31.7% in ADL. The PK profile was also comparable between the two treatment groups. CONCLUSION: SB5 was shown to be equivalent in terms of clinical efficacy when compared with ADL. SB5 was well tolerated with similar safety profile, PK, and immunogenicity to ADL.