Session Information
Date: Monday, November 9, 2015
Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy III: Biosimilars
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: SB4 is a biologic agent developed as a biosimilar of the etanercept reference product (ETN). This study was a randomized, double-blind, multicenter study and the equivalence of the primary endpoint (ACR20 at Week 24) was shown1. In this abstract, the results up to 52 weeks of the study comparing the long term efficacy, safety and immunogenicity, including radiographic progression, between SB4 and ETN are reported.
Methods: Patients with moderate to severe RA (according to the 1987 ACR criteria) despite MTX treatment were randomly assigned to receive weekly dose of 50 mg SB4 or ETN administered subcutaneously for 52 weeks. Efficacy, safety and immunogenicity outcomes were assessed up to Week 52 and radiographic damage was measured by the change in modified total sharp score (mTSS) from baseline to Week 52.
Results: A total of 596 patients with RA were randomized to either SB4 (N=299) or ETN (N=297) and 505 patients completed 52 weeks of treatment (SB4 N=259; ETN N=246). The ACR20 response rate at Week 52 was 80.8% vs. 81.5% in the per-protocol set (PPS) and 70.2% vs. 65.7% in the full analysis set (FAS) with non-responder analysis. The 95% confidence interval (CI) of the adjusted difference in ACR20 response rate was within [–15%, 15%] in both the PPS and FAS. The ACR50 and ACR70 response rates were also similar between SB4 and ETN (Table 1) and the mean change from baseline in mTSS was comparable between the two treatment groups (0.45 for SB4 and 0.74 for ETN).
The safety profile of SB4 was generally comparable to that of ETN (Table 2). Fewer injection site reactions were reported in the SB4 group compared to ETN and the incidence of anti-drug antibody was significantly lower in SB4 compared to ETN (p< 0.001).
Conclusion: Efficacy including radiographic progression and safety were comparable between SB4 and ETN up to Week 52. The immunogenicity profile was lower in SB4 compared to ETN.
Table 1. ACR Response Rates at Week 52 in the Full Analysis Set*
|
ACR response |
Treatment |
Response rate |
Adjusted difference rate** |
95% CI |
|
ACR20 |
SB4 |
70.2% (210/299) |
4.48% |
(–2.90%, 11.87%) |
|
ETN |
65.7% (195/297) |
|||
|
ACR50 |
SB4 |
47.8% (143/299) |
5.48% |
(–2.32%, 13.29%) |
|
ETN |
42.1% (125/297) |
|||
|
ACR70 |
SB4 |
30.4% (91/299) |
5.90% |
(–1.12%, 12.93%) |
|
ETN |
24.6% (73/297) |
|||
|
CI: confidence interval *FAS follows the intention-to-treat (ITT) principle and includes all patients with at least 1 dose of the study drug. Patients without response at Week 52 were considered as non-responders. **The difference rate was adjusted for baseline C-reactive protein and stratified by region. |
||||
Table 2. Safety and Immunogenicity Results
|
Patients with |
SB4 (N=299) |
ETN (N=297) |
||
|
n |
(%) |
n |
(%) |
|
|
At least 1 TEAE |
175 |
(58.5%) |
179 |
(60.3%) |
|
related |
88 |
(29.4%) |
109 |
(36.7%) |
|
At least 1 SAE |
18 |
(6.0%) |
15 |
(5.1%) |
|
related |
2 |
(0.7%) |
7 |
(2.4%) |
|
Serious infection |
1 |
(0.3%) |
5 |
(1.7%) |
|
Tuberculosis |
0 |
(0.0%) |
0 |
(0.0%) |
|
Injection site reactions* |
11 |
(3.7%) |
52 |
(17.5%) |
|
Malignancy |
4 |
(1.3%) |
1 |
(0.3%) |
|
Death |
2 |
(0.7%) |
0 |
(0.0%) |
|
At least 1 ADA positive test result up to Week 52 |
3 |
(1.0%) |
39 |
(13.2%) |
|
ADA: anti-drug antibody, SAE: serious adverse event, TEAE: treatment-emergent adverse event *Numbers are based on high-level group term of administration site reactions. |
||||
Reference
1. Vencovsky J et al. EULAR 2015, FRI0128
To cite this abstract in AMA style:
Vencovsky J, Sylwestrzak A, Leszczyñski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan V, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J, Emery P. A Phase III, Randomized, Double-Blind Clinical Study Comparing SB4, an Etanercept Biosimilar, with Etanercept Reference Product (Enbrel®) in Patients with Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy (52-week Results) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-phase-iii-randomized-double-blind-clinical-study-comparing-sb4-an-etanercept-biosimilar-with-etanercept-reference-product-enbrel-in-patients-with-moderate-to-severe-rheumatoid/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-phase-iii-randomized-double-blind-clinical-study-comparing-sb4-an-etanercept-biosimilar-with-etanercept-reference-product-enbrel-in-patients-with-moderate-to-severe-rheumatoid/