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.

ObjectivesSB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4.MethodsIn the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100.ResultsOf 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer.ConclusionsSB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.Trial registration numberNCT01895309; 2012-005026-30

ObjectiveTo compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA.MethodsIn a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated.ResultsA total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively.ConclusionEfficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN.Trial registration numberClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30

BackgroundSB4 is a biologic agent developed as a biosimilar of the etanercept reference product (ETN). Etanercept is approved for treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis, and paediatric plaque psoriasis in the EU.ObjectivesTo compare the efficacy, safety, and immunogenicity of SB4 with ETN in patients with moderate to severe RA despite methotrexate (MTX) treatment.MethodsPatients with moderate to severe RA despite MTX treatment were randomly assigned to receive weekly dose of 50 mg SB4 or ETN administered subcutaneously for 52 weeks. The primary endpoint was the ACR20 response rate at Week 24. Other endpoints including safety and immunogenicity were also measured.ResultsA total of 596 patients were randomised to either SB4 (N=299) or ETN (N=297). Baseline demographic and disease characteristics were comparable between two treatment groups. The ACR20 response rate at Week 24 in the per-protocol set (PPS) was 78.1% (193/247) in SB4 and 80.3% (188/234) in ETN. The 95% confidence interval (CI) of the treatment difference adjusted by region and baseline C-reactive protein was –9.41% to 4.98%, which was within the pre-defined equivalence margin of [–15%, 15%]. The ACR20 response rate at Week 24 was shown to be equivalent in the full analysis set as well (95% CI: −5.24%, 9.07%) when non-responder analysis was applied. The estimated difference between the time-response curves of SB4 and ETN in the PPS was contained within the pre-defined equivalence margin (Figure). The ACR50 response rates at Week 24 in the PPS were 46.6% vs. 42.3% and the ACR70 response rates were 25.5% vs. 22.6% in SB4 and ETN, respectively. The safety profile of SB4 was generally comparable to that of ETN (Table).Table 1.Safety resultsPatients withSB4 (N=299)ETN (N=297)n(%)n(%)At least 1 TEAE165(55.2%)173(58.2%)related83(27.8%)106(35.7%)At least 1 SAE13(4.3%)13(4.4%)related1(0.3%)6(2.0%)Serious infection1(0.3%)4(1.3%)Tuberculosis0(0.0%)0(0.0%)Injection site reactions*11(3.7%)51(17.2%)Malignancy3(1.0%)1(0.3%)Death1(0.3%)0(0.0%)SAE: serious adverse event; TEAE: treatment-emergent adverse event. *Numbers are based on high-level group term of administration site reactions.ConclusionsSB4 was shown to be equivalent in terms of clinical efficacy when compared with ETN. SB4 was well tolerated with a comparable safety profile to ETN.Disclosure of InterestJ. Vencovský Grant/research support from: Samsung Bioepis, Speakers bureau: UCB, Pfizer, AbbVie, MSD, A. Sylwestrzak Grant/research support from: Samsung Bioepis, P. Leszczyński Grant/research support from: Samsung Bioepis, Roche, MSD, Janssen, Novo Nordisk, UCB, Pfizer, Novartis, GSK, BHS, Consultant for: Samsung Bioepis, Roche, MSD, Paid instructor for: Novo Nordisk, Speakers bureau: MSD, UCB, Roche, Amgen, W. Porawska Grant/research support from: Samsung Bioepis, A. Baranauskaite Grant/research support from: Samsung Bioepis, V. Tseluyko Grant/research support from: Samsung Bioepis, V. Zhdan Grant/research support f...

BackgroundSB4 is approved by the European Medicines Agency as a biosimilar of the etanercept reference product (ETN). The phase I clinical study results and 52-week results of phase III clinical study have been reported previously.1–3ObjectivesTo evaluate the long term safety, immunogenicity, and efficacy of continuing SB4 vs. switching (as will occur in clinical practice) from ETN to SB4 in patients with moderate to severe RA.MethodsThe phase III randomised, double-blind study period consisted of 52 weeks of treatment with either weekly dose of subcutaneous 50 mg SB4 or ETN with background methotrexate (MTX) in patients with moderate to severe RA. After 52 weeks of treatment, patients in Czech Republic and Poland were enrolled into the open-label, extension period and received SB4 for additional 48 weeks. Efficacy, safety, and immunogenicity were assessed up to Week 100.ResultsAt Week 52, 245 patients from the randomised, double-blind study period enrolled into the extension study: 126 patients continued to receive SB4 (SB4/SB4) and 119 patients switched from ETN to SB4 (ETN/SB4). Among them, 119 (94.4%) patients of SB4/SB4 and 113 (95.0%) patients of ETN/SB4 completed 100 weeks of treatment. SB4 was well tolerated and the safety profile was comparable between SB4/SB4 and ETN/SB4 during the open-label, extension period (Table 1). Adverse events were those newly occurring after Week 52 in 47.6% of SB4/SB4 and 48.7% of ETN/SB4. There were no cases of injection site reactions reported after Week 52. The overall incidence of anti-drug antibodies after Week 52 was 0.8% in SB4/SB4 and 0.9% in ETN/SB4. Efficacy was sustained and comparable between SB4/SB4 and ETN/SB4 up to Week 100 (Table 2).ConclusionsSB4 was well tolerated and effective over 2 years in patients with RA. Efficacy, safety, and immunogenicity were comparable between the SB4/SB4 and ETN/SB4, demonstrating that switching produced no treatment emergent issues such as loss of efficacy, increase in adverse events, or increase in immunogenicity.ReferencesLee YJ et al. Ann Rheum Dis. 2015; 74 (Suppl2: 718), SAT0176Emery P et al. Ann Rheum Dis. 2015–207588 [Epub ahead of print]Vencovsky J et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 2055Disclosure of InterestP. Emery Consultant for: Samsung Bioepis, AbbVie, Pfizer, Merck, UCB, BMS, Sandoz, J. Vencovský Consultant for: Pfizer, servier, Samsung Bioepis, Eli Lilly, BMS, Novarti, Speakers bureau: UCB, Pfizer, AbbVie, MSD, A. Sylwestrzak Grant/research support from: Samsung Bioepis, P. Leszczyński Grant/research support from: Samsung Bioepis, W. Porawska Grant/research support from: Samsung Bioepis, B. Stasiuk Grant/research support from: Samsung Bioepis, J. Hilt Grant/research support from: Samsung Bioepis, Z. Mosterova Grant/research support from: Samsung Bioepis, S. Y. Cheong Employee of: Samsung Bioepis, J. Ghil Employee of: Samsung Bioepis