A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

Abstract

ObjectivesTo compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.MethodsThis is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured.Results596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was −9.41% to 4.98%, which is completely contained within the predefined equivalence margin of −15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%).ConclusionsSB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN.Trial registration numbersNCT01895309, EudraCT 2012-005026-30.

The EGALITY study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product in patients with moderate-to-severe chronic plaque-type psoriasis

“…Although the reasons for the lower incidence of ISRs cannot be fully elucidated, a possible reason could be the difference in formulation between the two products, as has been reported in other biosimilar studies. 21 The higher incidence of TEAEs of special interest reported with GP2015 during the study was not caused by an increased number of events in any specific system organ class, but was due to events spread across several system organ classes, with most occurring in just one patient each in the continued GP2015 group vs. none in the continued ETN group. Safety was not affected by switching treatments.…”

“…1): screening, treatment period 1 (weeks 0-12), treatment period 2 (weeks [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and an extension phase (weeks 31-52). In treatment period 1, patients were randomized 1 : 1 to self-administer 50 mg GP2015 or 50 mg ETN (Enbrel â ; Amgen Inc., Thousand Oaks, CA, U.S.A.; European Union authorized) twice weekly, subcutaneously.…”

“…17,18 Other biosimilar studies have also reported higher response rates for the primary efficacy parameter compared with the pivotal studies for the originator product. 21,[26][27][28] Moreover, the EGALITY study was designed to establish similarity between GP2015 and ETN …”

Biosimilars in oncology and inflammatory diseases: current and future considerations for clinicians in Latin America

“…SB4 was approved in regions including Australia, Canada, and the EU based on a submission containing data from a comparative trial in patients with RA, 106,121 while GP2015 has been approved in various markets, including the US, following an application encompassing the results of a trial in psoriasis. 101,122–125 In both cases, approval was granted for other eligible indications of the originator.…”

Editorial: Safety considerations of biosimilars

“…In a recent clinical trial of a biosimilar etanercept, the incidence of patients with anti-drug antibodies was lower with the biosimilar (0.7%) than with the reference drug (13.1%). 5 The significance of this finding has been debated, particularly the transient nature and limited duration of anti-drug antibody positivity observed in these patients. This example highlights the complexities in this area including the technical challenges associated with detecting and quantifying anti-drug antibodies, the timing of patient assessments compared to the original studies of the reference product, and the assessment of the clinical impact of anti-drug antibodies.…”