POS0184 EFFICACY OF BIIB059 ON SKIN MANIFESTATIONS IN PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN THE PHASE 2 LILAC STUDY (PART A)

Background SLE is a heterogeneous disease with diverse clinical presentations, and up to 70–80% of patients develop skin manifestations. 1–3 In SLE, plasmacytoid dendritic cells (pDCs), major source Type I interferon (IFN), accumulate in the skin. 4 Treatment BIIB059, humanized monoclonal antibody targeting blood cell antigen 2 (BDCA2) that expressed on pDCs, leads rapid internalization BDCA2 from surfaces pDCs inhibits production IFNs, pro-inflammatory cytokines, chemokines. 5 Part A randomized, two-part, Phase LILAC study ( NCT02847598 ) enrolled participants active joint disease. The primary endpoint was met, greater reduction total count at Week 24 BIIB059 treatment group vs placebo (PBO), more achieved ≥50% improvement baseline Cutaneous Lupus Erythematosus Disease Area Severity Index – Activity (CLASI-A) score PBO. 6 Objectives To further evaluate effect PBO reducing activity, as measured by various CLASI-A response thresholds. Methods Adults an diagnosis according revised ACR 1997 classification criteria, ≥4 tender swollen joints (28-joint assessment), (as defined 2000 [SLEDAI-2K]), positive anti-nuclear antibodies and/or anti-double-stranded DNA antibodies, were enrolled. Participants randomized receive 450 mg or PBO, administered subcutaneously every weeks additional dose 2. Improvements assessed ≥8. proportion achieving ≥7-point 24, CLASI-20, -50, -70, -90 responses over time. Achievement scores 0–1 also 24. These analyses used non-responder imputation logistic regression, without correction for multiplicity. proportions 0–3 resolution SLEDAI-2K rash evaluated ad hoc same population. Non-responder applied visits post failure discontinuation. Improvement British Isles Assessment Group index (BILAG-2004) B mucocutaneous domains similarly P-values calculated based odds ratios (ORs) compared Results At significantly receiving (n=39) (n=38) had (56.4% 34.2%, OR [95% confidence interval {CI}] 2.71 [1.03, 7.17], P=0.044). Numerically CLASI-50, CLASI-70, CLASI-90 (Figure 1). Similarly, who (25.6% 13.2%), (48.7% 28.9%). BIIB059- PBO-treated (28.6% 10.7%), similar findings seen BILAG-2004 domain. Conclusion reductions activity consistently observed disease, supporting potential benefit manifestations SLE. References [1]Dörner T, Furie R. Lancet 2019;393:2344–2358 [2]Patel J, et al. Curr Rheumatol Rep 2020;22:69 [3]Grönhagen C, 2010;19:1187–1194 [4]Vermi W, Immunobiology 2009;214:877–886 [5]Pellerin A, EMBO Mol Med 2015;7:464–476 [6]Furie R, Arthritis 2020;72(Suppl. 10):0935 (Abstract) Acknowledgements authors thank investigators their valuable contributions this study. This sponsored Biogen (Cambridge, MA, USA). Writing editorial support provided Selene Medical Communications (Macclesfield, UK), funded Biogen. Disclosure Interests Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: AstraZeneca, Biogen, BMS, Miltenyi, Grant/research from: UCB (research support; institutional grants); MSD, Roche (educational program grants), Richard Victoria Werth Kenneth Kalunian Amgen, Aurinia, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Nektar, Roche, Viela, Research Alliance, Sanford Consortium, XIAOBI HUANG Shareholder Employee Cristina Musselli Catherine Barbey NATHALIE FRANCHIMONT OMass Therapeutics,