FRI0239 Results of a phase 2b study of vobarilizumab, an anti-interleukin-6 receptor nanobody, as monotherapy in patients with moderate to severe rheumatoid arthritis

Background Vobarilizumab is a Nanobody® consisting of an anti-IL6 receptor domain and an anti-human serum albumin domain in development for treatment of RA. Objectives To assess the efficacy and safety of several dose regimens of vobarilizumab monotherapy administered subcutaneously to patients with active RA. Methods Patients with active RA who were intolerant to methotrexate (MTX) or for whom continued MTX treatment was inappropriate were randomized in a 1:1:1:1 ratio to 1 of the 3 blinded dose groups of vobarilizumab or to open-label tocilizumab (TCZ), all of which were given subcutaneously. Efficacy was evaluated descriptively at Week 12 using a number of widely accepted clinical endpoints. Adverse events and routine safety parameters including laboratory assessments were recorded. TCZ administered weekly or biweekly according to local labeling was included to obtain parallel descriptive information. Results The study enrolled 251 patients in Europe, Latin America and the United States. Baseline demographics and disease characteristics were well balanced across groups with mean DAS28 CRP between 5.9 and 6.2. At Week 12, 73% to 81% of the patients assigned to one of the vobarilizumab groups achieved an ACR20 response, while ACR50 and ACR70 response rates between 37 - 49% and 16 - 24%, respectively, were observed (see table). At the end of the 12-week treatment period, clinically meaningful improvement in HAQ-DI scores and remission based on DAS28 CRP and DAS28 ESR was observed in a substantial number of patients treated with vobarilizumab, either q4w or biweekly. Between 5% and 10% of the patients achieved remission defined by the more stringent CDAI or SDAI criteria. In total, 94% of patients randomized to open-label TCZ received drug weekly. In spite of this disparity in dosing frequency similar efficacy results were obtained in the vobarilizumab and TCZ groups. One vobarilizumab treated patient (225mg q2w treatment group, 1.6%) experienced a SAE during the treatment period as did 2 patients in the TCZ group (3.1%). Frequencies of treatment-emergent adverse events were similar across the groups. Of the vobarilizumab treated patients, 2.1% discontinued study drug due to TEAEs compared with 6% in the TCZ group. One case of severe hypersensitivity, not considered serious, was reported in the 225mg q2w treatment group. Liver function abnormalities were infrequent across all study groups. Grade 3 neutrophil toxicities were less commonly observed with vobarilizumab (1.1%) than with TCZ (4.3%). Conclusions In patients with active RA, treatment with vobarilizumab monotherapy had a positive impact on disease activity with no unexpected safety findings. Disclosure of Interest T. Dorner Consultant for: Ablynx, M. Weinblatt Consultant for: Ablynx, K. Van Beneden Employee of: Ablynx, E. Dombrecht Employee of: Ablynx, K. De Beuf Employee of: Ablynx, P. Schoen Employee of: Ablynx, R. Zeldin Employee of: Ablynx