Viatris Inc. (NASDAQ: VTRS) has announced the publication of Phase 2b CARE study results, revealing the efficacy and safety of cenerimod in treating adults with moderate-to-severe systemic lupus erythematosus (SLE). The study's findings, published in Lancet Rheumatology, indicate that cenerimod at a 4 mg dosage led to clinically meaningful and sustained improvements in SLE disease activity compared to a placebo, when used in conjunction with stable background SLE therapy.
CARE Study Design and Results
The CARE study was a Phase 2b, multicenter, randomized, double-blind, placebo-controlled trial involving adults aged 18-75 years with moderate-to-severe SLE. Of the 810 patients screened, 427 were randomly assigned to receive either once-daily oral cenerimod (0.5 mg, 1 mg, 2 mg, or 4 mg) or a placebo, in addition to their stable background SLE therapy, and were monitored for 12 months. The primary endpoint was the change from baseline to month 6 in the modified SLE Disease Activity Index 2K (mSLEDAI-2K) score.
Results from the CARE study showed that at month 6, the 4 mg cenerimod group exhibited the maximum response, with a least squares mean change from baseline in mSLEDAI-2K score of -4.04 (95% CI -4.79 to -3.28; difference vs placebo -1.19 [-2.25 to -0.12]; p=0.029). Furthermore, a subgroup analysis revealed that patients with a high IFN-1 gene expression signature treated with cenerimod 4 mg showed a greater reduction in mSLEDAI-2K at month 6 (-2.78) compared to placebo. This subgroup also demonstrated a 24% higher SLE Responder Index (SRI-4) response rate compared to placebo.
Cenerimod's Mechanism of Action
Additional results from the analysis of SLE-related biomarker data from the CARE study, published in the Annals of the Rheumatic Diseases, further elucidated cenerimod's mechanism of action. The data indicated that cenerimod 4 mg significantly reduced IFN-γ-associated proteins, as well as IFN-1 protein and gene expression signature biomarkers, after 6 months of treatment compared to placebo. This effect was more pronounced in patients with high IFN-1 expression, supporting the stronger clinical response observed in this population.
Philippe Martin, Viatris Chief R&D Officer, stated, "The biomarker data highlights the multifaceted immunomodulatory properties of cenerimod targeting key aspects of SLE pathogenesis."
Safety and Tolerability
Over the 12-month treatment and follow-up period, most adverse events (AEs) were mild to moderate, and no serious adverse events (SAEs) were related to cenerimod. The drug was generally well-tolerated at all doses evaluated.
Ongoing Phase 3 OPUS Program
The data from the CARE study informed the design and dose selection for the ongoing Phase 3 OPUS program (OPUS-1 NCT05648500, OPUS-2 NCT05672576, OPUS-OLE NCT06475742), which aims to evaluate the efficacy, safety, and tolerability of cenerimod in adult patients with moderate-to-severe SLE on top of background therapy. The primary endpoint of the OPUS program is the response on SRI-4 at month 12 compared to baseline.
About Cenerimod and SLE
Cenerimod is an investigational, highly selective sphingosine-1-phosphate 1 (S1P1) receptor modulator administered orally once daily. It targets SLE pathogenesis through immunomodulatory effects on lymphocytes, inflammation, and antigen transport. Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant immune system activity, including lymphocyte activation, autoantibody production, and activation of inflammatory cytokine pathways.
