PHASE lll CLINICAL STUDY4
STUDY DESlGN
N=596
Baseline to
Week 100
Phase 3 randomised double-blind multicentre study with open-label extension period (100 weeks) in RA patients from centres in the Czech Republic and Poland who continued after 52 weeks of treatment
ACR20 at Week 24 and the evaluation of long-term efficacy, safety and immunogenicity when continuing Benepali™ compared vs. switching from oETN to Benepali™
Numbers subsequent to initial randomisation are the numbers who completed the intended study timepoints (i.e. 24 weeks, 52 weeks, and 100 weeks). Efficacy analyses were undertaken in patients receiving ≥1 dose of study drug, therefore patient numbers may be higher than shown in the study design.
Primary endpoint (ACR20 at 24 weeks) and ACR response up to week 52
Benepali™ controlled disease activity as well as oETN3,4
Adapted from: Emery P, et al. 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis. Rheumatol (United Kingdom). 2017;56(12):2093–2101.
Abbreviations: ACR, American College of Rheumatology; ACR20/50/70, American College of Rheumatology 20%/50%/70% response criteria; oETN, originator etanercept.
Secondary endpoint
Benepali™ controlled disease activity as well as oETN2–5
Adapted from: Emery P, et al. Supplemental appendices to: Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017;76(12):1986–1991.
Abbreviations: DAS28, DAS28, 28-joint Disease Activity Score; oETN, originator etanercept; RA, rheumatoid arthritis; SD, standard deviation.
Benepali™ inhibited radiographic progression similarly to oETN to Week 1004
Adapted from: Emery P, et al. Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017;76(12):1986–1991.
Abbreviations: oETN, originator etanercept; mTSS, modified Total Sharp Score.
Benepali™ provided QoL benefit comparable to oETN5
Adapted from: Emery P, et al. Supplemental appendices to: Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017;76(12):1986–1991.
Abbreviations: oETN, originator etanercept; HAQ-DI, Health Assessment Questionnaire-Disability Index; QoL, quality of life; SD, standard deviation.
The immunogenicity profile of Benepali™ was comparable to that of oETN5
Adapted from: Emery P, et al. Supplemental appendices to: Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017;76(12):1986–1991.
Abbreviations: ADA, anti-drug antibody; oETN, originator etanercept.
Benepali cohort (n=126)
oETN cohort (n=119)
oETN/Benepali cohort
(switched to Benepali after 52 weeks) (n=119)
Comparable safety profile to oETN, with fewer injection-related adverse events at Week 242
| Preferred term | BenepaliTM 50 mg (n=299) n (%) |
oETN 50 mg (n=297) n (%) |
|---|---|---|
| Upper respiratory tract infection | 21 (7.0) | 15 (5.1) |
| Alanine aminotransferase increased | 15 (5.0) | 14 (4.7) |
| Nasopharyngitis | 14 (4.7) | 15 (5.1) |
| Headache | 13 (4.3) | 8 (2.7) |
| Hypertension | 10 (3.3) | 10 (3.4) |
| Aspartate aminotransferase increased | 7 (2.3) | 8 (2.7) |
| Viral infection | 7 (2.3) | 5 (1.7) |
| lnjection site erythema | 6 (2.0) | 33 (11.1) |
| Rheumatoid arthritis | 6 (2.0) | 9 (3.0) |
| Bronchitis | 6 (2.0) | 6 (2.0) |
| Diarrhoea | 5 (1.7) | 7 (2.4) |
| Pharyngitis | 4 (1.3) | 8 (2.7) |
| Urinary tract infection | 4 (1.3) | 7 (2.4) |
| Lymphocyte count decreased | 4 (1.3) | 6 (2.0) |
| Cough | 3 (1.0) | 10 (3.4) |
| Erythema | 2 (0.7) | 10 (3.4) |
| Dizziness | 2 (0.7) | 7 (2.4) |
| lnjection site rash | 2 (0.7) | 6 (2.0) |
| lnjection site reaction | 1 (0.3) | 7 (2.4) |
Adapted from: Emery P, et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017;76(1):51–57.
Abbreviations: oETN, originator etanercept.