State‐of‐the‐art immunogenicity evaluation in phase 3 confirmatory study (<scp>EGALITY</scp>) with etanercept biosimilar <scp>GP</scp>2015

Poetzl, Johann; Arlt, I.; Richter, Oliver von; Wöhling, Heike; Afonso, M.C.; Schaffar, Gregor

doi:10.1111/jdv.14632

Cited by 5 publications

(6 citation statements)

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“… 33 Applying both a sensitive and drug-tolerant assay as well as a contemporary biostatistical approach may lead to a higher reported ADA incidence compared with historical data. 17 While ADA incidence was consistently low in the GP2015 treatment group, a singular peak of ADA positivity was observed at week 4 for ETN-treated patients also including NAbs. Beside the evaluation of ADA/NAb incidence, a correlation of immunogenicity outcome to efficacy or patients’ safety was not observed, indicating that detected ADAs were not clinically relevant.…”

Section: Discussionmentioning

confidence: 86%

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Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study

et al. 2018

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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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Section: Discussionmentioning

confidence: 86%

“…The applied method for the detection of ADAs is based on a bridging electrochemiluminescence assay format 17 including acid dissociation steps. Study samples were first analysed in a screening assay based on a 5% false-positive rate.…”

Section: Methodsmentioning

confidence: 99%

Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study

et al. 2018

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“…In the EGALITY study, ADAs were evaluated using a validated state‐of‐the‐art technique implying a high assay sensitivity according to FDA's draft guideline and high drug tolerance above the highest measured drug concentration of the study. The bioanalytical strategy for immunogenicity assessment followed a tiered approach, and included a screening assay, a confirmatory specificity assay and a competitive ligand binding assay to assess the neutralizing capacity of ADAs …”

Section: Discussionmentioning

confidence: 99%

Multiple switches between GP2015, an etanercept biosimilar, with originator product do not impact efficacy, safety and immunogenicity in patients with chronic plaque‐type psoriasis: 30‐week results from the phase 3, confirmatory EGALITY study

Gerdes¹,

Thaçi

Griffiths

et al. 2017

Acad Dermatol Venereol

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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.

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“…A false-positive rate for confirmatory assay of 1% was applied, as recommended recently [20], instead of the commonly used 0.1% rate [21]. Previous reports have shown that applying a sensitive as well as a drug-tolerant assay may lead to a higher reported incidence of ADA compared with historical data [14].…”

Section: Discussionmentioning

confidence: 99%

“…Safety assessments included evaluation of the adverse events (AEs) as well as the local tolerability of injection sites of both medications as assessed by the investigator during the study. Immunogenicity assessment included analysis of anti-drug antibodies (ADAs) up to 48 weeks using a validated screening, confirmatory, and titer determination electrochemiluminescence bridging assay [14].…”

Section: Methodsmentioning

confidence: 99%

Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study

Jaworski¹,

Matucci‐Cerinic

Schulze‐Koops

et al. 2019

Arthritis Res Ther

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Background Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis. Methods EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10–25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24. Results The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between “continued SDZ ETN” (− 2.90 [0.12], n = 148) and “switched to SDZ ETN” (− 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the “continued SDZ ETN” and 38.0% in the “switched to SDZ ETN” groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected. Conclusions The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept. Trial registration EudraCT number 2012-002009-23 , Registered 19 April 2012—prospectively registered. Electronic supplementary material The online version of this article (10.1186/s13075-019-1907-x) contains supplementary material, which is available to authorized users.

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State‐of‐the‐art immunogenicity evaluation in phase 3 confirmatory study (EGALITY) with etanercept biosimilar GP2015

Cited by 5 publications

References 5 publications

Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study

Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study

Multiple switches between GP2015, an etanercept biosimilar, with originator product do not impact efficacy, safety and immunogenicity in patients with chronic plaque‐type psoriasis: 30‐week results from the phase 3, confirmatory EGALITY study

Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study

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