POS0699 GREATER REDUCTION IN CLASI-A SCORES ACHIEVED WITH BIIB059 VERSUS PLACEBO INDEPENDENTLY OF DISEASE SEVERITY AT BASELINE
Authors: V. Werth, R. Furie, K. Kalunian, R. Van Vollenhoven, S. Navarra, F. Nyberg, J. Romero-Diaz, M. Tee, X. Huang, H. Carroll, C. Barbey, C. Musselli, N. Franchimont
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with cutaneous lupus erythematosus (CLE) experience symptoms including photosensitivity, rash, pain, and skin damage that can impact their quality of life. No targeted therapies are approved for CLE. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen-2 (BDCA2), expressed exclusively on the surface of plasmacytoid dendritic cells (pDCs). The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the cell surface of pDCs, thereby inhibiting the production of pDC-derived type I interferons, cytokines, and chemokines, which are involved in CLE pathology. In Part B of the 2-part, phase 2 LILAC study ( NCT02847598 ), the primary endpoint was met: BIIB059 significantly reduced CLE activity, as evidenced by a statistically significant dose response and statistically significant differences in least-squares mean percent changes in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity (CLASI-A) score 1 versus placebo. 2 Objectives: To determine the proportion of patients with CLE who presented at baseline with moderate or severe disease (CLASI-A ≥ 10) or with the higher category of mild disease (CLASI-A &lt; 10 [i.e., 8 or 9]) and experienced a shift in CLASI-A score to a mild skin disease category or clear/almost clear skin status. Methods: Adults with histologically confirmed CLE with or without systemic manifestations were enrolled if they had CLASI-A ≥ 8 at baseline, despite prior use of or intolerance to topical corticosteroids (CS) and/or antimalarials, in addition to ≥ 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). Concomitant CLE/SLE therapy was allowed if doses were initiated ≥ 12 weeks and kept stable ≥ 4 weeks before randomization and throughout the treatment period. Systemic corticosteroid 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 for 12 weeks, with an additional dose at Week 2. An ad hoc analysis was conducted to determine the proportion of participants (CLASI-A ≥ 10 or &lt; 10 at baseline) with a shift in CLASI-A score to ≤ 1, ≤ 3, ≤ 6, and ≤ 8 at Week 16. Results: In this ad hoc analysis from LILAC Part B, 106 (80.3%) and 26 (19.7%) of participants had a baseline CLASI-A score ≥ 10 and &lt; 10, respectively. Compared with placebo, higher proportions of participants treated with BIIB059 achieved a shift in CLASI-A score from either ≥ 10 or &lt; 10 at baseline to ≤ 1, ≤ 3, ≤ 6, and ≤ 8 at Week 16 (Figure 1). Treatment with BIIB059 resulted in higher proportions of participants achieving reduced scores, indicating shifts to more mild disease activity, compared with placebo. A score ≤ 1 (clear or almost clear skin) at Week 16 was achieved by 0.0% (0/25), 5.0% (1/20), 14.3% (3/21), and 12.5% (5/40) of participants with baseline CLASI-A ≥ 10 who were treated with placebo and BIIB059 50, 150, and 450 mg, respectively. Two of 26 participants with baseline CLASI-A &lt; 10 achieved a score ≤ 1 (both received BIIB059 150 mg). Conclusion: A greater proportion of participants achieved milder skin disease or clear/almost clear skin status in the BIIB059 groups as compared with the placebo group. This effect was observed in participants with moderate or severe disease as well as in those in the higher range of the mild category of disease severity at baseline, indicating the ability of BIIB059 to improve skin lesions in patients with a broad range of cutaneous disease activity. References: [1]Albrecht J, et al. J Invest Dermatol . 2005;125(5):889-894. [2]Werth V, et al. Arthritis Rheumatol . 2020;72(suppl 10). Abstract 0986. Acknowledgements: This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was from Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen. Disclosure of Interests: Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Richard Furie Consultant of: AstraZeneca, Biogen, Grant/research support from: AstraZeneca, Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Sandra Navarra Speakers bureau: Astellas, Johnson &amp; Johnson, Novartis, Pfizer, Consultant of: Biogen, Filippa Nyberg Consultant of: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Michael Tee Speakers bureau: Pfizer, Novartis, Johnson &amp; Johnson, Celltrion, Consultant of: Neovacs, Grant/research support from: Celltrion, Johnson &amp; Johnson, Pfizer, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen