Session Information
Date: Tuesday, October 23, 2018
Title: Rheumatoid Arthritis – Treatments Poster III: Biosimilars and New Compounds
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Clinical equivalence of BI 695501 to the adalimumab RP has been shown in pts with moderately-to-severely active RA in the Phase III VOLTAIRE®-RA study (NCT02137226), through similar American College of Rheumatology 20% (ACR20) responses at Weeks (wks) 12, 24 and 48 (Cohen et al 2018. ARD doi:10.1136/annrheumdis-2017-212245). Here we present long-term safety, efficacy and immunogenicity data.
Methods: This 48-wk, open-label, multicenter, Phase IIIb extension study (VOLTAIRE®-RAext, NCT02640612) included 430 adults with moderately-to-severely active RA who wished to continue, and could benefit from continuing (per investigator’s assessment), treatment with BI 695501 following participation in the VOLTAIRE®-RA study. All pts received 40 mg BI 695501 self-administered via pre-filled syringe every 2 wks. The primary endpoint was proportion of pts with drug-related adverse events (AEs) from the start of VOLTAIRE®-RAext to end of 10 wks’ follow-up. Secondary efficacy endpoints included change from baseline in Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate (ESR), and proportion of pts achieving EULAR response, ACR/EULAR remission and ACR20 response at Wk 48 (using VOLTAIRE®-RA baseline as reference). Further endpoints included ACR50/70.
Results: All 430 pts in this study received BI 695501; 225 from the BI 695501 continuous (BI 695501-CONT), 102 from the adalimumab RP to BI 695501 switch at 24 wks (SWITCH), and 103 from the adalimumab RP continuous (RP-CONT) arms of VOLTAIRE®-RA. Baseline demographics were balanced across treatments arms in the parent study. A total of 87 (20.2%) pts experienced ≥1 drug-related AE, with a slightly lower proportion in the SWITCH arm (n=18; 17.6%) compared with BI 695501-CONT (n=48; 21.3%) and RP-CONT (n=21; 20.4%) arms (Table 1). 26 (6.0%) pts experienced ≥1 serious AE and 1 pt (BI 695501-CONT arm) experienced AEs leading to death (investigator assessed as not drug-related). Anti-drug antibody (ADA) and neutralizing antibody (nAb) data were similar between treatment arms. At Wk 48, clinical efficacy was similar irrespective of treatment arm in the parent study (Table 2). 42 (9.8%) and 36 (8.4%) pts prematurely discontinued the trial and treatment, respectively.
Conclusion: No new safety or immunogenicity findings were identified in this extension study. The clinical efficacy observed at wk 48 in VOLTAIRE®-RA (Cohen et al 2018. ARD doi:10.1136/annrheumdis-2017-212245) was sustained for up to 2 years in pts in the BI 695501-CONT arm, 72 wks in pts in the SWITCH arm, and 1 year in pts who switched to BI 695501 when entering VOLTAIRE®-RAext.
| Table 1. Overview of treatment-emergent AEs* during VOLTAIRE®-RAext (SAF) | ||||
| Pts, n (%) | BI 695501-CONT (n = 225) |
SWITCH (n = 102) |
RP-CONT (n = 103) |
Total (n=430) |
| ≥1 AE | 116 (51.6) | 34 (33.3) | 43 (41.7) | 193 (44.9) |
| ≥1 drug-related AE | 48 (21.3) | 18 (17.6) | 21 (20.4) | 87 (20.2) |
| ≥1 serious AE | 14 (6.2) | 4 (3.9) | 8 (7.8) | 26 (6.0) |
| AE leading to study drug discontinuation | 7 (3.1) | 2 (2.0) | 7 (6.8) | 16 (3.7) |
| AE = treatment-emergent adverse event.
SAF = safety analysis set. |
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| Table 2. Clinical efficacy at Wk 48 (FAS) | ||||
| BI 695501-CONT (n = 225) |
SWITCH (n = 101†) |
RP-CONT (n = 103) |
Total (n=429) |
|
| Mean change in DAS28-ESR, from baseline* | –3.01 | –2.98 | –2.91 | –2.98 |
| EULAR response, n (%)*
Good Moderate No response |
85 (37.8) 112 (49.8) 21 (9.3) |
42 (41.6) 52 (51.5) 3 (3.0) |
39 (37.9) 56 (54.4) 6 (5.8) |
166 (38.7) 220 (51.3) 30 (7.0) |
| ACR/EULAR remission, n (%) | 19 (8.4) | 7 (6.9) | 10 (9.7) | 36 (8.4) |
| ACR20 response, n (%)* | 174 (77.3) | 75 (74.3) | 80 (77.7) | 329 (76.7) |
| ACR50 response, n (%)* | 126 (56.0) | 52 (51.5) | 56 (54.4) | 234 (54.5) |
| ACR70 response, n (%)* | 72 (32.0) | 30 (29.7) | 35 (34.0) | 137 (31.9) |
| FAS = full analysis set.
* VOLTAIRE®-RA baseline used as the baseline reference point † One pt from the SWITCH arm was excluded from the FAS due to not having ≥1 DAS28 or ACR20 measurement during the trial. |
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To cite this abstract in AMA style:
Cohen S, Czeloth N, Lee E, Klimiuk PA, Peter N, Jayadeva G. Biosimilar BI 695501 and Adalimumab Reference Product (RP) Have Similar Efficacy and Safety in Patients (pts) with Moderately-to-Severely Active Rheumatoid Arthritis (RA): Long-Term Results from a Phase IIIb Extension Study (VOLTAIRE®-RAext) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/biosimilar-bi-695501-and-adalimumab-reference-product-rp-have-similar-efficacy-and-safety-in-patients-pts-with-moderately-to-severely-active-rheumatoid-arthritis-ra-long-term-results-from-a-pha/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/biosimilar-bi-695501-and-adalimumab-reference-product-rp-have-similar-efficacy-and-safety-in-patients-pts-with-moderately-to-severely-active-rheumatoid-arthritis-ra-long-term-results-from-a-pha/