FRI0114 EFFICACY OF LEVILIMAB, NOVEL MONOCLONAL ANTI-IL-6 RECEPTOR ANTIBODY, IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 1-YEAR RESULTS OF PHASE 2 AURORA STUDY
Authors: V. Mazurov, E. Zotkin, E. Ilivanova, T. Kropotina, T. Plaksina, O. Nesmeyanova, N. Soroka, A. Kundzer, A. Lutskii, E. Dokukina, A. Eremeeva, A. Zinkina-Orihan
Journal: Annals of the Rheumatic Diseases (2020)

Background: Previously, 12-week results of phase 2 clinical study of levilimab (LVL) in patients with active rheumatoid arthritis (RA) have been reported 1 . The study has met the primary endpoint at W12 confirming that treatment with LVL 162 mg SC + methotrexate (MTX) either QW or Q2W is superior to MTX alone in patients with RA and inadequate response to methotrexate (MTX-IR). Here we report 1-year efficacy and safety data in QW and Q2W arm of the study. Objectives: This study was aimed to assess the efficacy and safety of 2 dosing regimens of LVL in active MTX-IR RA subjects. Methods: This multicenter double-blind placebo-controlled study ( NCT03455842 ) enrolled 105 MTX-IR subjects with active RA (ACR2010). The study design is outlined on Figure 1. Secondary endpoints for the open-label period included ACR20/50/70, LDA, remission rates, and DAS28-CRP(4), among others. The safety was evaluated up to W56. Figure 1. Study design Results: At W12 ACR20 was reached by 77.1% and 57.1% of subjects of QW and Q2W arms respectively. Within open-label (OLE) period further increase in clinical response degree was observed up to W52, more pronounced in ACR50 and even more in ACR70 / RA LDA and Remission rates (Table 1). Figure 1 summarizes the dynamic of DAS28-CRP(4) change throughout the study. QW regimen showed better efficacy results. Table 1. Efficacy results (full analysis set), n (%). QW + MTX (n = 35 ) Q2W + MTX (n = 35 ) p-value ACR20 W12 27 (77.1) 20 (57.1) 0.07 W52 32 (91.4) 25 (71.4) 0.03 ACR50 W12 18 (51.4) 11 (31.4) 0.09 W52 26 (74.3) 23 (65.7) 0.43 ACR70 W12 10 (28.6) 7 (20.0) 0.40 W52 23 (65.7) 16 (45.7) 0.09 LDA (DAS28 &lt;3.2) W12 20 (57.1) 10 (28.6) 0.02 W52 29 (82.9) 24 (68.6) 0.16 EULAR Remission W24 4 (11.4) 2 (5.7) 0.67 W52 10 (28.6) 10 (28.6) 1.00 Table 2 shows the main safety endpoints for the entire study (W0 – W56). The most common treatment related AEs (registered &gt;5% of subjects) were laboratory abnormalities (neutrophil count decrease, ALT / AST increase, blood cholesterol/triglycerides increased). SAE occurred within the blinded study period were reported previously 1 . During OLE, starting from W12, four new serious AE (SAEs) were reported: 3 in LVL QW arm: haemorrhage (gr.3, unrelated), vaginal cyst (gr.3, unrelated) and keratitis (gr.2, unrelated); 1 in LVL Q2W arm: myocardial ischemia with cardiovascular insufficiency (gr.5, unrelated). Table 2. Safety results (full analysis set, W0 – W56), n (%). QW + MTX (n = 35) Q2W + MTX (n = 35) Any TEAEs/SAEs 34 (97.1) 29 (82.9) Any SAEs 4 (11.4) 2 (5.7) Any gr. 3-4 AEs 16 (45.7) 12 (34.3) Gr. 3-4 neutropenia 4 (11.4) 5 (14.3) AEs of special interest (ALT / AST high; Leucopenia / Neutropenia; Infections; Cholesterol/triglycerides high ) 28 (80.0) 26 (74.3) Treatment discontinuation due to AE 0 4 (11.3) Deaths 0 2 (5.7) (unrelated) Conclusion: Within 1 year of treatment LVL + MTX showed sustained efficacy, with continuous clinical improvement in MTX-IR subjects with active RA. The safety profile of LVL was consistent with other IL6R inhibitors. LVL QW regimen was shown to be safe with better efficacy in terms of time and magnitude and was selected for phase 3 confirmatory clinical study. References: [1]http://dx.doi.org/10.1136/annrheumdis-2019-eular.7220 Figure 2. Absolute DAS-28-CRP(4) change (median ± IQR, full analysis set) Disclosure of Interests: V Mazurov: None declared, 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 Grant/research support from: JSC BIOCAD, Alena Kundzer: None declared, Anton Lutskii Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD