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.

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.

BackgroundGP2015 is a proposed etanercept (tumor necrosis factor inhibitor) biosimilar.ObjectivesTo compare the pharmacokinetics (PK) and safety of GP2015 and etanercept originator product (EU-authorised) in healthy subjects.MethodsHealthy subjects (N=54) were randomised to receive a single 50 mg subcutaneous (sc) injection of GP2015 or etanercept originator product, followed by a wash-out period of at least 35 days, and a single 50 mg sc injection of originator product or GP2015, respectively. Subsequent follow up was 28 days. The primary PK parameters were normalised by the protein content of the administered dose before fitting in the analysis of variance model (dose normalised PK analysis). Bioequivalence between GP2015/etanercept originator product for primary PK parameters [maximum observed serum concentration (Cmax), area under the serum concentration-time curve measured from the time of dosing to the last measurable concentration (AUC0-tlast) and AUC measured from the time of dosing and extrapolated to infinity (AUC0-inf)] was demonstrated if the 90% confidence intervals (CIs) for the ratio of geometric means were completely contained within the predefined bioequivalence limits of 0.80–1.25.ResultsThe 90% CIs for the ratios of geometric means of dose normalised primary PK parameters (Cmax, AUC0-tlast and AUC0-inf) were within the interval of 0.80–1.25 (Table). For the respective nominal dose (not dose normalised) primary PK parameters, the 90% CIs of the ratios of geometric means were also within the interval of 0.80–1.25 (Table). The most common AEs regardless of relationship to study drug were neutropenia [GP2015, n=7 (13%); originator product, n=8 (14.8%)], headache [GP2015, n=5 (9.3%); originator product, n=5 (9.3%)] and nasopharyngitis [GP2015, n=4 (7.4%); originator product, n=4 (7.4%)]. All treatment-related AEs were of mild or moderate intensity. No serious AEs and deaths occurred during the study. Three subjects had low titer and non-neutralising anti-drug antibodies (ADAs) at the 28-day follow-up visit (treatment sequence GP2015/etanercept originator product).ConclusionsThis study demonstrated PK bioequivalence between GP2015, a proposed etanercept biosimilar and the etanercept originator product with no relevant differences in safety. The safety and immunogenicity profiles observed in this study are consistent with previous reports on etanercept originator product.Disclosure of InterestM. Afonso Employee of: Hexal AG, affiliate of Novartis, S. Sanguino Heinrich Employee of: Hexal AG, affiliate of Novartis, J. Poetzl Employee of: Hexal AG, affiliate of Novartis, H. Woehling Shareholder of: Hexal AG, affiliate of Novartis, Employee of: Hexal AG, affiliate of Novartis

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