LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Background Tyrosine kinase 2 (TYK2) mediates signaling of Type I interferons, IL-23, and IL-12, key cytokines involved in lupus pathogenesis. Deucravacitinib (DEUC) is an oral, selective, allosteric TYK2 inhibitor with a unique mechanism action, distinct from Janus (JAK) 1/2/3 inhibitors, has shown efficacy psoriasis psoriatic arthritis. Objectives Assess safety DEUC patients active systemic erythematosus (SLE). Methods This was 48-week (wk), randomized, double-blind, placebo (PBO)-controlled, phase trial ( NCT03252587 ). Eligible met SLICC criteria, were seropositive (ANA/anti-dsDNA/anti-Sm), had SLEDAI-2K score ≥6 ≥1 BILAG index A or >2 B manifestations the musculoskeletal mucocutaneous domain. Patients on standard background medications randomized 1:1:1:1 to PBO (3 mg BID, 6 12 QD). Oral corticosteroid tapering 7.5 mg/day required wks 8-20; further optional 32-40. The primary endpoint proportion achieving SRI(4) at wk 32. Key secondary endpoints 48 included SRI(4), BICLA, LLDAS, CLASI-50, change baseline (tender swollen) joint count. Results total 363 demographic disease characteristics similar across treatment groups. Of patients, 275 (76%) completed treatment. 32 met, significantly greater 3 BID groups vs responses (PBO: 34.4%; BID: 58.2%, P =0.0006; 49.5%, =0.021; QD: 44.9%, =0.078). response sustained all up (Figure 1). At 48, group demonstrated statistical significance count, two other clinically meaningful differences Rates adverse events (AEs), serious AEs, AEs interest between (Table Most common (≥10%) upper respiratory tract infection, nasopharyngitis, headache, urinary infection. No deaths, major cardiac events, thrombotic opportunistic infections, tuberculosis occurred. Malignancies rare rates abnormalities mean levels hematology chemistry laboratory parameters observed. Table 1. Summary Adverse Events Through Week AE, n (% ) Placebo = 90 91 93 QD 89 AE 79 (87.8) 85 (93.4) 81 (87.1) 75 (84.3) SAE 11 (12.2) 7 (7.7) 8 (8.6) (7.9) leading discontinuation (3.3) (8.8) (6.5) (12.4) Skin-related b (13.3) 15 (16.5) (34.4) 30 (33.7) Overall infections/infestations (53.3) 60 (65.9) (64.5) 45 (50.6) Serious 1 (1.1) (2.2) Infections Tuberculosis 0 Herpes zoster c 4 (4.4) (3.2) Influenza (3.4) COVID-19 5 (5.4) Malignancy d e f MACE Thrombotic number who experienced event. Includes (≤8.6% any arm) acne, rash, dermatitis acneiform, pruritus, skin lesion, urticaria. herpes zoster, ophthalmic, genital zoster. Basal cell carcinoma. Breast Vaginal squamous event; COVID-19, coronavirus 2019; DEUC, deucravacitinib; MACE, events; SAE, Conclusion In SLE, showed statistically significant clinical improvement multiple composite organ-specific measures wks, well tolerated. shows promise as novel therapy for SLE warrants investigation trials. Acknowledgements study sponsored by Bristol Myers Squibb. Professional medical writing assistance provided Julianne Hatfield, PhD Peloton Advantage, LLC, OPEN Health company, Parsippany, NJ, USA, funded authors acknowledge Christina Crater, MD, employed Squibb time conducted, contributions conduct. Disclosure Interests Eric Morand Consultant of: AstraZeneca, Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, Servier, Novartis , Grant/research support from: AbbVie, Amgen, Janssen, UCB Marilyn Pike Pfizer, Joan T. Merrill UCB, GlaxoSmithKline, Remegen, Celgene/Bristol Aurinia, Astellas, Alexion, Sanofi, Zenas, Provention GlaxoSmithKline AstraZeneca Ronald van Vollenhoven Biotest, Celgene, Galapagos, Gilead, Paid instructor for: Roche, Speakers bureau: Victoria P. Werth Medimmune, Resolve, Idera, Medscape, Nektar, Incyte, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kirin, GSK, Cugene, Corcept, Beacon Bioscience Viela, Lupus Research Alliance/BMS Coburn Hobar Shareholder Employee Nikolay Delev Vaishali Shah Brian Sharkey Thomas Wegman Ian Catlett Subhashis Banerjee Shalabh Singhal