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Abstract Number: 0608

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

Anca Askanase1, David D'Cruz2, Kenneth Kalunian3, Joan Merrill4, Sandra Navarra5, Clélia Cahuzac6, Peter Cornelisse6, Daniel Strasser6, Luba Trokan7 and Ouali Berkani8, 1Columbia University Medical Center, New York, NY, 2Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 3University of California San Diego, La Jolla, CA, 4Oklahoma Medical Research Foundation, Oklahoma City, OK, 5University of Santo Tomas Hospital, Joint and Bone Center, Manila, Philippines, 6Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland, 7Idorsia Pharmaceuticals Ltd. at time of data generation, Allschwil, Switzerland, 8IDORSIA, Allschwil, Switzerland

Meeting: ACR Convergence 2023

Keywords: Autoantibody(ies), interferon, Systemic lupus erythematosus (SLE)

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Session Information

Date: Sunday, November 12, 2023

Title: (0582–0608) SLE – Treatment Poster I

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Cenerimod is an orally active, selective sphingosine 1-phosphate (S1P) 1 receptor modulator under investigation for the treatment of systemic lupus erythematosus (SLE). In the Phase 2 CARE study (NCT03742037), patients treated with cenerimod 4 mg showed reduced disease activity versus placebo after 6 months.1

Type-1 interferon (IFN-1) activation is a robust biomarker of SLE disease activity, and an elevated IFN-1 signature associates with autoantibodies and more active disease. Cenerimod reduces plasma levels of IFN-α and leads to decreased circulating B and T cells in patients with SLE, suggesting effects on innate and acquired immune responses.

Here the efficacy of cenerimod in patients with high IFN-1 gene expression signature and high anti-dsDNA antibody levels is presented, as reported at EULAR 2023.2

Methods: CARE randomized 427 patients with SLE to once-daily cenerimod (0.5, 1, 2, 4 mg) or placebo. At month (M) 6, patients on 4 mg cenerimod were re-randomized to placebo or cenerimod 2 mg for the remaining 6 months; other groups continued their initially assigned treatment to M12. The primary endpoint was change from baseline to M6 in SLEDAI-2K score modified to exclude leukopenia (mSLEDAI-2K) due to the mechanism of action of cenerimod.

Subgroup analyses were performed in patients with high IFN-1 gene expression signature (based on expression of IFI27, RSAD2, HERC5, and IFIT1) or anti-dsDNA levels ≥30 IU/mL.

Results:

At baseline, 207/408 patients (51%) in CARE had high IFN-1 gene expression signature [including 36 (45%) and 40 (50%) on cenerimod 4 mg and placebo, respectively], and 86/426 (20%) had anti-dsDNA antibody levels ≥30 IU/mL [21 (25%) and 15 (17%) for cenerimod 4 mg and placebo, respectively]. There was an association between high IFN-1 gene expression signature and high anti-dsDNA levels, with more than 75% of patients with anti-dsDNA levels ≥30 IU/mL having high IFN-1 gene expression signature.

Cenerimod 4 mg resulted in decreased levels of anti-dsDNA antibodies and IFN-a protein at M6 versus baseline. In patients with high IFN-1 gene expression signature or high anti-dsDNA, 4 mg cenerimod led to greater reductions of disease activity versus placebo, as measured by mSLEDAI and SRI-4 at M6.

More patients with high IFN-1 gene expression signature at baseline had resolution of arthritis and alopecia at M6 in the treatment arm versus patients with the low IFN-1 gene expression signature (Table 1).

Conclusion: Treatment with cenerimod 4 mg resulted in greater reduction of disease activity versus placebo at M6 in patients with baseline high IFN-1 gene expression signature or high anti-dsDNA antibody levels. Cenerimod treatment also reduced levels of IFN-α protein and anti-dsDNA antibodies in these patients. Two Phase 3 studies designed to evaluate the treatment effect of cenerimod 4 mg in SLE are underway.

References
1. Askanase A et al. Arthritis Rheumatol 2022;74(Suppl 9):3293–7.
2. Adapted by permission from BMJ Publishing Group Limited. Askanase A et al. DOI: 10.1136/annrheumdis-2023-eular.3823.

Acknowledgements Medical writing support was provided by Anne Sayers and funded by Idorsia Pharmaceuticals Ltd.

Supporting image 1

Table 1. Resolution of alopecia and arthritis (assessed by SLEDAI) at Month 6 by baseline IFN_1 gene expression signature. IFN_1, interferon 1. Overall population refers to all randomized patients.


Disclosures: A. Askanase: AbbVie, 2, Amgen, 2, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb, 2, Celgene, 2, Eli Lilly, 2, Genentech, 2, GSK, 2, Idorsia, 2, Janssen, 2, Mallinckrodt, 2, Pfizer, 2, UCB Pharma, 2; D. D'Cruz: GlaxoSmithKlein(GSK), 1, 2, Idorsia Pharmaceuticals Ltd, 1, 2, UCB, 1, 2, Vifor, 1, 2; K. Kalunian: AbbVie/Abbott, 2, Amgen, 5, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, EquilliumBio, 2, Genentech, 2, Gilead, 2, Janssen, 2, KezarBio, 1, Merck/MSD, 2, Novartis, 2, Pfizer, 2, Remegene, 2, Roche, 2, UCB, 5; J. Merrill: AbbVie, 2, Alexion, 2, Alumis, 2, Amgen, 2, AstraZeneca, 2, 5, Aurinia, 2, Bristol Myers Squibb, 2, 5, EMD Serono, 2, Genentech, 2, Gilead, 2, GlaxoSmithKline, 2, 5, Lilly, 2, Merck, 2, Pfizer, 2, Provention, 2, Remegen, 2, Sanofi, 2, UCB Pharma, 2, Zenas, 2; S. Navarra: Astellas, 6, AstraZeneca, 6, Biogen, 2, Boehringer-Ingelheim, 2, GSK, 6, Novartis, 6, Pfizer, 6; C. Cahuzac: Idorsia Pharmaceuticals Ltd, 3, 11; P. Cornelisse: Idorsia Pharmaceuticals Ltd, 3, 11; D. Strasser: Idorsia Pharmaceuticals Ltd, 3, 11; L. Trokan: Idorsia Pharmaceuticals Ltd, 3, 11; O. Berkani: Idorsia Pharmaceuticals Ltd, 3, 11.

To cite this abstract in AMA style:

Askanase A, D'Cruz D, Kalunian K, Merrill J, Navarra S, Cahuzac C, Cornelisse P, Strasser D, Trokan L, Berkani O. 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 [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/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/. Accessed .
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