Background/Purpose: FKB327 is a proposed biosimilar of the adalimumab RP. A randomized, DB, Phase 3 study (NCT02260791) compared the efficacy, safety, pharmacokinetics (PK) and immunogenicity of FKB327 and RP in pts with active RA inadequately controlled on methotrexate (MTX). This was followed by a randomized OLE study with treatment switching (NCT02405780) which assessed long-term safety, efficacy, PK and immunogenicity.

Methods: Pts aged ≥18 years with moderate to severe, active RA (2010 ACR criteria) for ≥3 months and taking MTX for ≥3 months (10–25 mg/week stable dose for ≥8 weeks) were enrolled. In the DB study, pts were randomized 1:1 to FKB327 or RP (40 mg subcutaneously [sc]) every other week (eow) with continuing MTX. The primary endpoint was ACR20 response rate at Week 24 with prespecified equivalence margins of −12 to +15% for a two-sided 90% confidence interval (CI), recommended by the FDA. Secondary endpoints included DAS28-CRP at Week 24 and ACR20/50/70 response rates over time. Safety was assessed by the incidence/severity of adverse events (AEs) and laboratory abnormalities. In the OLE, pts completing the DB study with clinical response and no serious AEs were immediately re-randomized to FKB327 or RP so that two-thirds of pts remained on the same treatment as in the DB study and one-third switched to the alternate treatment (40 mg sc eow) for Weeks 0–28 (Part 1), then all received FKB327 to Week 76 (Part 2). The primary endpoint was safety. Interim analysis of the OLE was performed when results of approximately 100 patient-years’ continuous treatment were available on both products.

Results: In the DB study, 728 pts from 12 countries were treated with FKB327 (n=366) or RP (n=362). Demographics and baseline RA characteristics were similar between the groups, with mean MTX dose of 15.8 mg/week (standard deviation [SD] 4.8) and mean RA duration of 8.5 years (SD 8.0). ACR20 response rate at Week 24 (non-responder imputation, full analysis set) was comparable (FKB327 72.5%; RP 74.3%); 90% CI (–7.3, 3.6) fell within prespecified equivalence margins. DAS28-CRP at Week 24 and ACR20/50/70 response rates over time were highly comparable. Safety profiles, mean serum trough drug concentration at steady state, and prevalence/ titer of anti-drug antibodies (ADAs) were all well-matched. Re-randomization in the OLE resulted in 645 pts receiving the following treatment sequences across the DB then OLE (Part 1) studies: FKB327–FKB327, n=216; RP–RP, n=213; FKB327–RP, n=108; and RP–FKB327, n=108. At interim analysis, safety profiles were comparable for all treatment sequences, although group sizes were reduced after switching. ACR20 response rate at Week 30 was comparable after continuous (FKB327–FKB327, 82.5%; RP–RP, 84.3%) and switched (FKB327–RP, 86.5%; RP–FKB327, 89.1%) treatment. No consistent differences in PK and ADA profiles were seen between continuous and switched treatments.

Conclusion: The DB study met its primary equivalency endpoint for ACR20 response rate at Week 24; safety, ADA and PK profiles also supported the comparability of FKB327 and RP in pts with active RA. Interim OLE results suggested that long-term safety, efficacy, PK and immunogenicity of FKB327 and RP were comparable on continuous and switched treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-safety-and-immunogenicity-in-randomized-double-blind-db-and-open-label-extension-ole-studies-comparing-fkb327-an-adalimumab-biosimilar-with-the-adalimumab-reference-product-humira/