A PHASE 2 TRIAL OF INTRAVENOUS LY2127399, AN ANTI-BAFF MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO TNF-ALPHA INHIBITORS

Background: LY2127399 (LY), a human monoclonal antibody, neutralizes membrane-bound and soluble B cell activating factor (BAFF), an essential survival factor for peripheral B lymphocytes. LY previously showed clinical efficacy in patients with active rheumatoid arthritis(RA) . Objectives: To test the safety and efficacy of intravenous (IV) LY in patients (pts) with active RA and inadequate response to TNFα inhibitors. Methods: 98 RA pts with a history of inadequate response or intolerance to ≥1 TNFα inhibitor were randomized to receive placebo (Pb; n=35), 30mg (n=35) or 80mg (n=28) of LY administered as an IV infusion at 0, 3, and 6 weeks (wks). The primary outcome was the proportion of pts achieving ACR50 response among all pts treated with LY compared to Pb at wk16 (1-sided Fisher's exact test). Results: Baseline characteristics were similar between groups. At wk16 no significant difference was seen for the combined LY group versus Pb in ACR50 (12.7% vs 2.9%, p=0.10) or ACR20 (27.0% vs 17.1%, p=0.20) responses. Significant differences were seen at wk6 and 9 for ACR20/50 (figure) and wk9 for change in DAS28 and CRP. The decline in efficacy from wk9 to wk16 coincided with decreasing exposure to LY which had declined by 97% at wk16 (t1/2 ≈2 weeks). Differences in efficacy were also seen based on region of the world studied. In LY groups total B cells increased within 1wk then decreased to below baseline by wk16 predominantly due to changes in mature naïve (IgD+/CD27-) cells. Treatment emergent adverse events (AEs) occurred in 63% (30mg), 75% (80mg) and 71% (Pb) pts. Infections occurred more frequently in LY groups (29% vs 17%). Serious AEs occurred in 2 (7.1%) pts receiving 80mg LY and 3 (8.6%) pts receiving Pb. One serious infection occurred in a patient on Pb. Reductions from baseline to wk16 in IgM and IgA (p<0.05) but not IgG were significant in the combined LY group compared to Pb and were not related to the occurrence of infection. Figure 1 Conclusions: The LY safety profile was similar to other RA therapies and had no unexpected safety signals. Although the primary 16wk endpoint was not met, clinical efficacy was observed at wk9. The decline in efficacy may be related to LY clearance. These results support further studies of LY in this pt population. References: 1. Genovese MC et al. [abstract]. Arthritis Rheum 2009;60 Suppl 10:1923 Disclosure of Interest: M. Genovese Grant/Research support from: Eli Lilly and Co, Consultant for: Eli Lilly and Co, R. Fleischmann Grant/Research support from: Eli Lilly and Co, Consultant for: Eli Lilly and Co, M. Greenwald Grant/Research support from: Eli Lilly and Co, M. Veenhuizen Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, J. Satterwhite Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, L. Xie Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, P.-Y. Berclaz Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, S. Myers Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, O. Benichou Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and CoCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 611Session: Rheumatoid arthritis – other biologic treatment (Poster Presentations )