THU0150 Long-Term Safety and Efficacy of SB4 (Etanercept Biosimilar) in Patients with Rheumatoid Arthritis: Comparison between Continuing SB4 and Switching from Etanercept Reference Product To SB4

Abstract

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

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…The NOR-SWITCH infliximab trial was conducted across six indications and used a non-inferiority margin of 15% (adapted from rheumatoid arthritis studies), with results suggesting no loss of efficacy and no unexpected treatment-emergent adverse events (TEAEs) [53]. Eight studies reported similar outcomes between groups, but failed to provide a formal statistical analysis of between-group comparisons [55, 56, 69, 70, 75, 98, 102–104]. …”

“…Percentage achieving good or moderate EULAR-ESR and EULAR-CRP responses similar between groups for each time point (week 8, 16 and 24)CT-P10/CT-P10 vs rituximab/CT-P10, AE: 24 vs 20%; SAE: 3 vs 5%; infusion-related reaction: 3 vs 5%; infection: 8 vs 10%CT-P10/CT-P10 vs rituximab/CT-P10: 13 vs 15% (all since pre-switch). nADAs, n  = 1Emery et al 2016 (abstract) [101, 102]With rheumatoid arthritis ( N  = 245)119ETN RP, 52 weeks (study also included patients on SB4 throughout, with no switch)SB4, 48 weeksWeeks 52–100, ETN RP/SB4 vs SB4/SB4, ACR20: 79 vs 78%; ACR50: 61 vs 60%; ACR70: 42 vs 43% (statistical analysis NR)Weeks 52–100, ETN RP/SB4: ≥ 1 TEAE, n  = 58 (49%); ≥ 1 SAE, n  = 2 (2%); serious infections, n  = 1 (1%); death, n  = 0 (0%); SB4/SB4: ≥ 1 TEAE, n  = 60 (48%); ≥ 1 SAE, n  = 6 (5%); serious infections, n  = 1 (1%); death (from hepatic cancer), n  = 1 (1%)Weeks 52–100, ETN RP/SB4: n  = 1 (1%); SB4/SB4: n  = 1 (1%)Griffiths et al 2017 [103]With chronic plaque psoriasis ( N  = 531)196GP2015 or ETN, 12 weeks (study also included patients re-randomised to same treatment, with different dosing schedule, with no switch)Patients with PASI improvement ≥ 50% re-randomised to series of 3 treatment switches to week 30, then continuation on last assigned treatment to week 52Baseline to week 52, mean scores and percentage changes in PASI score at all time points similar between continued GP2015 and ETN groups, and between pooled continued and pooled switched groups. Response rates increased over time in all treatment groups until week 30 and then remained stable to week 52≥1 TEAE up to week 52, continued GP2015 vs continued ETN switched GP2015 vs switched ETN: 60 vs 57 vs 61 vs 59%.…”

Biosimilars already approved and in development

“…Of these, 119 patients in the maintenance group and 113 switched patients continued to week 100. Efficacy and radiographic progression were sustained and comparable between groups, with response rates of 77.9% in maintained patients and 79.1% in switched patients for ACR20; 59.8% and 60.9%, respectively, for ACR50; and 42.6% and 41.7%, respectively for ACR70 10. The safety profiles between weeks 52 and 100 were also similar, with at least one TEAE reported in 47.8% of patients in the SB4 arm and 48.7% of those in the Enbrel arm.…”

“…This was a typical example of a biosimilar study, with a 52 week randomised double blind period followed by an open label extension period up to week 100 in which all patients received SB4 and methotrexate allowing evaluation of a single switch from a bio-originator to the biosimilar 9. The double blind period included 596 patients, but the extension period was carried out only in Poland and the Czech Republic and included 245 patients 10. The primary endpoint was American College of Rheumatology 20 (ACR20) response rate at week 24.…”

Biosimilars: considerations for clinical practice

“…The results showed no loss of efficacy for up to 100 weeks, with a similar efficacy observed in the switching and maintenance groups (table 2). 33 Furthermore, switching did not result in any treatment emergent problems or an increase in adverse events or immunogenicity (table 2). 33 Overall, SB4 was well tolerated and effective over 2 years in patients with rheumatoid arthritis 33…”