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OP0193 (2020)
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)
V. Werth1, R. Furie2, J. Romero-Diaz3, S. Navarra4, K. Kalunian5, R. Van Vollenhoven6, F. Nyberg7, B. Kaffenberger8, S. Sheikh9, G. Radunovic10, X. Huang11, H. Carroll11, F. Gaudreault11, A. Meyers11, C. Barbey12, C. Musselli11, N. Franchimont11, on behalf of the LILAC Investigators
1University of Pennsylvania, Philadelphia, United States of America
2Northwell Health, Great Neck, United States of America
3Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico
4University of Santo Tomas, Manila, Philippines
5UCSD, La Jolla, United States of America
6Amsterdam School of Medicine, Amsterdam, Netherlands
7Karolinska University Hospital, Stockholm, Sweden
8Ohio State University, Columbus, United States of America
9University of North Carolina, Chapel Hill, United States of America
10Institute of Rheumatology, Belgrade, Serbia
11Biogen, Cambridge, MA, United States of America
12Biogen, Baar, Switzerland

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.

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 & 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

Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 120
Session: Dendritic cells as therapeutics (Oral Presentations)