Background/Purpose: No approved targeted therapies have been developed for cutaneous lupus erythematosus (CLE), a disfiguring autoimmune disease that severely impairs quality of life.¹ BIIB059 is a humanized monoclonal antibody that binds blood dendritic cell antigen 2 (BDCA2), a receptor uniquely expressed on plasmacytoid dendritic cells, leading to BDCA2 internalization and subsequent inhibition of inflammatory mediator production, most notably type I IFNs.² LILAC (NCT02847598) was a 2-part, phase 2 study investigating the efficacy and safety of BIIB059. Part A enrolled SLE participants. Part B, presented here, is the largest interventional study to date in CLE participants.

Methods: To be eligible for enrollment, adults with histologically confirmed CLE must have had active CLE defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score ≥8 despite prior use of or documented intolerance to topical CS and/or antimalarials and ≥1 lesion diagnostic of subacute CLE (CLASI-A erythema score ≥2) and/or chronic CLE (CLASI-A erythema score ≥2 and CLASI-Damage scarring score ≥1); all with or without systemic manifestations. Concomitant CLE/SLE therapy was allowed if doses were initiated ≥12 weeks and kept stable ≥4 weeks prior to randomization and throughout the treatment period; systemic CS doses could not exceed 15 mg/day of prednisone (or equivalent). BIIB059 (50, 150, 450 mg) or placebo was subcutaneously administered once every 4 weeks, with an additional dose at week 2, for 12 weeks. The primary endpoint was a multiple comparison procedure–modeling test of dose response in % change in CLASI-A score from baseline to week 16. Secondary endpoints included proportion of participants with a 50% improvement in CLASI-A score (CLASI-50 response rate) and ≥7-point reduction in CLASI-A score from baseline over time. Safety was assessed throughout the study.

Results: Of 33, 26, 25, and 48 participants dosed in the placebo and BIIB059 50, 150, and 450 mg groups, respectively, 93.9%, 88.5%, 96.0%, and 87.5% completed treatment. The study met its primary endpoint, demonstrating a dose response (p=0.0005) and statistically significant differences in least squares mean % changes (SE) in CLASI-A score between the placebo vs. BIIB059-treated participants (Table 1). Meaningful clinical improvements in secondary skin-related efficacy endpoints were observed in the BIIB059 groups. AEs and serious AEs (SAEs) for the placebo and pooled BIIB059 groups occurred in 66.7% vs. 71.7% and 9.1% vs. 7.1%, respectively (Table 2). Three (3.0%) BIIB059 participants and no placebo participants had AEs of hypersensitivity. Herpes zoster meningitis was observed in 1 participant (BIIB059 50 mg) after study completion.

Conclusion: BIIB059 significantly reduced disease activity in CLE with an acceptable safety profile. Further development of BIIB059 for the treatment of CLE is warranted.

1. Ogunsanya. Br J Dermatol. 2017;176:52; 2. Pellerin. EMBO Mol Med. 2015;7:464

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/biib059-a-humanized-monoclonal-antibody-targeting-blood-dendritic-cell-antigen-2-on-plasmacytoid-dendritic-cells-shows-dose-related-efficacy-in-a-phase-2-study-in-participants-with-active-cutaneous/