OP0193 BIIB059, A HUMANIZED MONOCLONAL ANTIBODY TARGETING BDCA2 ON PLASMACYTOID DENDRITIC CELLS (PDC), SHOWS DOSE-RELATED EFFICACY IN THE PHASE 2 LILAC STUDY IN PATIENTS (PTS) WITH ACTIVE CUTANEOUS LUPUS ERYTHEMATOSUS (CLE)
Authors: V. Werth, R. Furie, J. Romero-Diaz, S. Navarra, K. Kalunian, R. Van Vollenhoven, F. Nyberg, B. Kaffenberger, S. Sheikh, G. Radunovic, X. Huang, H. Carroll, F. Gaudreault, A. Meyers, C. Barbey, C. Musselli, N. Franchimont
Journal: Annals of the Rheumatic Diseases (2020)

Background: CLE represents an unmet medical need with no approved therapy. BIIB059, a humanized monoclonal antibody, binds to BDCA2 and inhibits pro-inflammatory mediators production, including type I interferons. BIIB059 was evaluated in Phase 1 studies NCT02106897 and NCT03224793 . LILAC is a 2-part Phase 2 study: Part A enrolled SLE pts; Part B enrolled pts with active CLE ( NCT02847598 ). Objectives: Evaluate efficacy and safety of BIIB059 in pts enrolled in Part B at Week 16, end of treatment (EOT) period. Methods: Pts with active CLE, SCLE and/or CCLE and adjudicated Cutaneous Lupus Disease Area and Severity Index – Activity (CLASI-A) ≥8 were enrolled and randomized to receive either BIIB059 (50, 150 or 450 mg) or placebo (PBO) s.c. Q4W. Primary endpoint was dose response defined by % change in CLASI-A score from baseline (BL) to Week 16. Secondary endpoints included CLASI-50 response rate and ≥ 7-point reduction in CLASI-A score from baseline to EOT. Adverse events and serious adverse events were recorded throughout the study. Results: 132 pts with active CLE were randomized. The study met its primary endpoint, demonstrating a dose response (p= 0.0005) and a statistically significant difference in % change from BL in CLASI-A score in BIIB059-treated pts vs PBO. Table 1 and Table 2 summarize efficacy and safety results, respectively. Table 1. Efficacy Endpoints BIIB059 PBO 50 mg 150 mg 450 mg LS Mean (SE ) LS Mean (SE ) LSMD * from PBO (95% CI ) P val. LS Mean(SE ) LSMD * from PBO (95% CI ) P val. LS Mean (SE ) LSMD * from PBO (95% CI ) P val. Primary Endpoint CLASI-A % change from BL -14.5 (6.4) -40.8 (7.5) -26.3 (-45.7; -7.0) 0.008 -47.9 (7.4) -33.5 (-52.7; -14.3) 0.001 -43.5 (5.5) -28.0 (-44.5; -11.5) 0.001 Secondary Endpoints n(%) n(%) LSMD* from PBO (95% CI) P val. n(%) LSMD* from PBO (95% CI) P val. n(%) LSMD* from PBO (95% CI) P val. Prop. of participants achieving CLASI 50 7/32 (21.9%) 10/26 (38.5%) 15.8% (-7; 39) 0.133 11/25 (44.0%) 21 (-2.8; 45) 0.059 20/43 (46.5%) 23 (3; 44) 0.024 Prop. of participants achieving a ≥7-point CLASI-A reduction from BL 7/32 (21.9%) 9/26 (34.6%) 12.3 (-11.3; 35.8) 0.228 12/25 (48.0%) 22.2 (-2.0; 46.3) 0.055 18/43 (41.8%) 16.8 (-6.7; 40.4) 0.048 *LSMD=LS Mean Difference PBO BIIB059 OVERALL N=33 50 mg N=26 150 mg N=25 450 mg N=48 Pooled N=99 N=132 Any Event, n(%) 18 (54.5) 17 (65.4) 12 (48) 33 (68.8) 62 (62.6) 80 (60.6) Severity Mild 11 (33.3) 11 (42.3) 8 (32.0) 19 (39.6) 38 (38.4) 49 (37.1) Moderate 4 (12.1) 6 (23.1) 3 (12.0) 12 (25.0) 21 (21.2) 25 (18.9) Severe 3 (9.1) 0 1 (4.0) 2 (4.2) 3 (3.0) 6 (4.5) Related events 6 (18.2) 9 (34.6) 4 (16.0) 16 (33.3) 29 (29.3) 35 (26.5) Serious events 2 (6.1) 0 3 (12.0) 2 (4.2) 5 (5.1) 7 (5.3) Related serious events 1 (3.0) 0 1 (4.0) 1 (2.1) 2 (2.0) 3 (2.3) Events leading to drug withdrawal 0 1 (3.8) 1 (4.0) 1 (2.1) 3 (3.0) 3 (2.3) Events leading to study withdrawal 0 0 0 1 (2.1) 1 (1.0) 1 (0.8) Fatal events 0 0 0 0 0 0 Conclusion: BIIB059 administration to pts with active CLE resulted in statistically significant dose-related improvement in disease activity vs PBO with no untoward safety signals. Further development of BIIB059 in CLE is warranted. Disclosure of Interests: Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Juanita Romero-Diaz Consultant of: Biogen, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson &amp; Johnson, Abbvie, Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Filippa Nyberg Consultant of: Biogen, Benjamin Kaffenberger Grant/research support from: Amgen, Biogen, InflaRx, Veloce Biopharmaceuticals, Dermatology Foundation, Saira Sheikh: None declared, Goran Radunovic: None declared, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Francois Gaudreault Shareholder of: Biogen, Employee of: Biogen, Adam Meyers 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, Employee of: Biogen