FRI0108\u2005SHORT-TERM EFFICACY OF BCD-089, NOVEL MONOCLONAL ANTI-IL-6 RECEPTOR ANTIBODY, IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 12-WEEK RESULTS OF PHASE 2 AURORA STUDY

Abstract

Background: In the previous phase 1 study BCD-089 (INN: levilimab) was well-tolerated, had favorable safety profile and low immunogenicity1. Here we report 12-week efficacy and safety results of ongoing phase 2 clinical study of BCD-089 in patients with active RA. Objectives: This study is aimed to assess efficacy and safety of 2 dosing regimens of BCD-089 in patients with MTX-IR active RA. Methods: During this multicenter double-blind placebo-controlled randomized clinical study (NCT03455842) 105 MTX-IR patients with active RA (ACR2010) were assigned (1:1:1) to receive 162 mg of BCD-089 s.c. (QW arm and Q2W arm) or PBO. MTX (10-25 mg/week) was used in all groups. After completion of 12-week blinded period patients from QW/Q2W arms continued the treatment, patients from PBO arm were switched to BCD-089 Q2W until Wk56. The primary efficacy endpoint was the rate of ACR20 at Wk12. Secondary endpoints included ACR50/70 and DAS28-CRP(4). The safety was routinely evaluated. Results: The efficacy analysis showed that 95% confidence interval for BCD-089 treatment effect relative to PBO was [38.45 – 81.55] for QW arm and [16.53 – 63.4] for Q2W arm, which confirms the superiority to PBO of either dosing regimens. Summary of efficacy results is presented in table 1. The majority of adverse events (AE) were laboratory abnormalities. The spectrum of AEs is similar to other IL6R inhibitors (Table 2). Three serious AE (SAEs) were reported: community-acquired pneumonia (QW arm, treatment-related), acute cholecystitis (PBO arm, not related, did not lead to treatment discontinuation), and acute heart failure leading to death (Q2W arm, not related). One case of moderate local reaction (erythema) was reported in QW arm. Conclusion: BCD-089 in combination with MTX had superior efficacy compared with MTX plus PBO in MTX-IR patients with active RA. BCD-089 showed safety profile consistent with other IL6R inhibitors. Further clinical studies are needed. Reference: [1] Khlyabova P, et al. doi: 10.1136/annrheumdis-2018-eular.2410Table 1 Safety results (full analysis set), n (%) Efficacy parameter BCD-089 QW+MTX (n=35) BCD-089 Q2W+MTX (n=35) PBO+MTX (n=35) p-value (Fisher’s exact test) ACR20 27 (77.1%) 20 (57.1%) 6 (17.1%) <0.0001 ACR50 18 (51.4%) 11 (31.4%) 2 (5.7%) 0.0001 ACR70 10 (28.6%) 7 (20.0%) 1 (2.9%) 0.0106 DAS28-CRP(4) < 3.2 20 (57.1%) 10 (28.6%) 1 (2.9%) <0.0001Table 2 Safety results (full analysis set), n (%) Safety parameter BCD-089 QW+MTX (n=35) BCD-089 Q2W+MTX (n=35) PBO+MTX (n=35) Any AE 26 (74.29%) 23 (65.71%) 14 (40.0%) Any SAE 1 (2.86%) 1 (2.86%) 1 (2.86%) Any grade 3-4 AE 10 (28.57%) 6 (17.14%) 2 (5.71%) Grade 3-4 Neutropenia 3 (8.57%) 3 (8.57%) 0 (0.00%) AE of special interest ALT/ AST increased 4 (11.43%) 5 (14.29%) 1 (2.86%) Leucopenia/ Neutropenia 5 (14.29%) 6 (17.14%) 1 (2.86%) Infections and infestations 2 (5.71%) 1 (2.86%) 2 (5.71%) Total cholesterol increased 8 (22.86%) 8 (22.86%) 2 (5.71%) AEs leading to treatment discontinuation 0 (0.00%) 1 (2.86%) 0 (0.00%) Deaths 0(0.00%) 1(2.86%) 0(0.00%) Disclosure of Interests: V Mazurov Grant/research support from: JSC BIOCAD, Evgeniy Zotkin: None declared, Elena Ilivanova Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Nikolaj Soroka: None declared, Alena Kundzer: None declared, Anton Lutskii Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Ekaterina Chernyaeva Employee of: JSC BIOCAD, Roman Ivanov Employee of: JSC BIOCAD