POS1147 EFFICACY OF CENERIMOD IN PATIENTS WITH HIGH IFN-1 GENE EXPRESSION SIGNATURE AND HIGH ANTI-DSDNA ANTIBODY LEVELS: POST-HOC ANALYSIS FROM A PHASE 2 STUDY

Background Cenerimod is an orally active, selective sphingosine 1-phosphate (S1P) 1 receptor modulator under investigation for the treatment of systemic lupus erythematosus (SLE). The Phase 2 CARE study ( NCT03742037 ) did not meet its primary endpoint after adjustment multiplicity, but patients treated with cenerimod 4 mg showed reduced disease activity versus placebo 6 months. [1] Along prior findings that type-1 interferon (IFN-1) activation a robust biomarker SLE and elevated IFN-1 signature associates autoantibodies more severe disease, reduces plasma levels IFN-α leads to decreased circulating B T cells in SLE, suggesting effects on both innate acquired immune responses. Objectives These post-hoc analyses evaluated efficacy subpopulations SLE. Methods randomised 427 once-daily (0.5, 1, or mg) placebo. At month (M) 6, receiving were re-randomised subsequent months, while all other groups continued their initially assigned M12. was change from baseline M6 SLEDAI-2K score modified exclude leukopenia (mSLEDAI-2K) due mechanism action cenerimod. Post-hoc performed high gene expression anti-dsDNA ≥30 IU/mL. based four genes IFI27 , RSAD2 HERC5 IFIT1 ). Results Primary results presented at ACR 2022. met (nominal P=0.0291 vs placebo). baseline, 207 (51%) had signature, including 36 (45%) 40 (50%) placebo, respectively. Anti-dsDNA antibody IU/mL noted 86 (20%), 21 (25%) 15 (17%) There association between levels, than 75% having signature. Reduction mSLEDAI-2K group greater overall population (Figure 1A). Similarly, proportion SRI-4 responders higher low (70% 41% mg; 46% 43% Patients baseline. resolution alopecia reported by (38% 26% 14% 7% placebo), as arthritis (57% 28% 38% 42% placebo) reduction mucosal ulcers (80% 67% mSLEDAI-2K. However, there no effect observed rash. Conclusion Treatment resulted reductions also protein antibodies these patients. Two 3 studies are underway. Reference [1]Askanase A et al. Efficacy Safety Moderate Severe Systemic Lupus Erythematosus (SLE): Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Finding 2b Trial. Arthritis Rheumatol 2022; 74 (suppl 9):3293–7. Figure 1. least-square mean (95% CI) Month group. Acknowledgements o This sponsored Idorsia Pharmaceuticals Ltd. Medical writing support provided Anne Sayers (Idorsia Ltd.) funded We thank participation investigators involvement patient care contribution study. Disclosure Interests Anca Askanase Consultant of: Abbvie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer. Provention, Remegen UCB, David D’Cruz Vifor, Kenneth Kalunian Biogen, Equillium, Genentech/Roche, Gilead, KangPu, Kezar, Novartis, Pfizer, Joan Merrill AbbVie, Alexion, Alumis, Astra Zeneca, Bristol Myers Squibb, EMD Serono, GlaxoSmithKline, Merck, Remegen, Sanofi, Zenas, Grant/research from: Sandra Navarra Speakers bureau: Roche, Astellas, Boehringer Ingelheim, Horizon Pharma, Clélia Cahuzac Employee Ltd., Peter Cornelisse Daniel Strasser Luba Trokan Ouali Berkani