SummaryBackground GP2015 is a proposed etanercept biosimilar. Objectives To demonstrate equivalent efficacy, and comparable safety and immunogenicity of GP2015 and the etanercept originator (ETN, Enbrel â ) in patients with

Background EGALITY was a phase III confirmatory efficacy and safety study conducted in patients with plaque‐type psoriasis as a part of totality of evidence gathered during the development of GP2015, an etanercept biosimilar.ObjectiveTo demonstrate equivalent efficacy and comparable safety and immunogenicity of GP2015 and the etanercept originator product (ETN, Enbrel®) and evaluate effects of repeated switching between GP2015 and ETN. Results for efficacy, safety and immunogenicity during treatment period (TP) 2 (TP2) are presented pooling the two continued treatment arms (pooled continued) versus the two treatment arms with repeated switches (pooled switched).MethodsPatients (n = 531) were randomized 1:1 to self‐administer GP2015 or ETN twice‐weekly subcutaneously during TP1. Patients with a ≥50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were re‐randomized for TP2 to continue the same treatment at once‐weekly dosing or to undergo three consecutive treatment switches between GP2015 and ETN until week 30. Patients continued the last‐assigned treatment during TP2, until week 52.ResultsMean (standard deviation [SD]) PASI scores at baseline were similar in patients who underwent multiple switches compared to those with continued treatments during TP2. During TP2, PASI 50, PASI 75 and PASI 90 response rates, percent change from baseline in PASI scores and all other efficacy parameters were similar between the pooled switched and pooled continued treatment groups at all time points. The incidence of treatment‐emergent adverse events including injection site reactions was comparable between the pooled switched (36.7%) and pooled continued (34.9%) groups. None of the patients in either treatment group were positive for binding anti‐drug antibodies in TP2.ConclusionTreatment efficacy, safety and immunogenicity were similar between the pooled continued and pooled switched treatments during TP2, indicating that there are no effects in the short term on clinical data of multiple switches between GP2015 and ETN.

ObjectivesTo demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs).MethodsIn the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50  mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10–25  mg/week) until end of the study. The 24-week results are presented here.ResultsEquivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of −0.6 to 0.6. The least squares mean difference (GP2015–ETN) in change from baseline in DAS28-CRP up to week 24 was −0.07 (95% CI −0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively.ConclusionIn patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN.Trial registrationNCT02638259.

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AimsTo assess pharmacokinetics (PK) and safety of GP2015, a proposed etanercept biosimilar, in two studies: comparison with etanercept originator (ETN, bioequivalence study) and comparison of GP2015 administered via an autoinjector (AI) or prefilled syringes (PFS, delivery study).MethodsBoth studies were randomized, two‐sequence, two‐period, crossover studies conducted in healthy male subjects. In the bioequivalence study, subjects were randomized to receive a single 50 mg subcutaneous (s.c.) injection of GP2015 or ETN. In the delivery study, subjects were randomized to receive a single 50 mg s.c. injection of GP2015 via AI or PFS. Following a wash‐out period of 35 days, subjects in the bioequivalence study received single 50 mg s.c. injection of GP2015 or ETN, and subjects in the delivery study received single 50 mg s.c. injection of GP2015 via AI or PFS.ResultsThe geometric mean ratios (90% confidence interval) of GP2015/ETN for Cmax (1.11 [1.05–1.17]), AUC0–tlast (0.98 [0.94–1.02]) and AUC0–inf (0.96 [0.93–1.00]) were within the predefined bioequivalence range of 0.80–1.25. The geometric mean ratios (90% confidence interval) of AI/PFS for Cmax (1.01 [0.94–1.08]), AUC0–tlast (1.01 [0.95–1.07]) and AUC0–inf (1.01 [0.96–1.07]) were also within the range 0.80–1.25. No new safety issues were reported. Three subjects had low titres of non‐neutralising anti‐drug antibodies during a follow‐up visit in the bioequivalence study.ConclusionsThe PK of GP2015 was similar to ETN, demonstrating bioequivalence. The safety profile of GP2015 was consistent with previous reports for ETN. The GP2015 AI provided equivalent dosing and tolerability to the GP2015 PFS.