Viatris announced the publication of Phase 2b CARE study results evaluating the efficacy and safety of cenerimod in adults with moderate-to-severe systemic lupus erythematosus (SLE). The findings, published in Lancet Rheumatology, demonstrated that cenerimod 4 mg provided clinically meaningful and sustained improvements in SLE disease activity compared to placebo when combined with stable background therapy. Cenerimod was well tolerated, with an adverse event profile consistent with its mechanism of action.
In addition to these results, an analysis of the CARE study focusing on SLE-related biomarker data was published in the Annals of the Rheumatic Diseases. This secondary publication further elucidated the mechanism of action of cenerimod in patients with SLE.
“We are pleased our Phase 2b CARE study results were published in two prominent journals, Lancet Rheumatology and Annals of the Rheumatic Diseases, which underscores the urgent need for novel agents for the treatment of SLE, like cenerimod,” said Viatris Chief R&D Officer Philippe Martin. “The biomarker data highlights the multifaceted immunomodulatory properties of cenerimod targeting key aspects of SLE pathogenesis.”
The insights from these publications informed the design and dose selection for the ongoing Phase 3 OPUS program, which includes OPUS-1 (NCT05648500), OPUS-2 (NCT05672576), and OPUS-OLE (NCT06475742).
CARE Study Design
The CARE study was a double-blind, randomized, placebo-controlled Phase 2b trial. It involved adults aged 18-75 years with moderate-to-severe SLE. Of the 810 patients screened, 427 were randomly assigned (1:1:1:1:1) to receive once-daily oral cenerimod at doses of 0.5 mg, 1 mg, 2 mg, or 4 mg, or placebo, in addition to stable background therapy. Patients were followed for 12 months. The primary endpoint was the change from baseline to month 6 in the mSLEDAI-2K score for cenerimod versus placebo.
Key Results
- Primary Endpoint: At month 6, the 4 mg dose group achieved 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). This represented a statistically significant difference compared to placebo (−1.19; 95% CI −2.25 to −0.12; p=0.029).
- Subgroup Analysis: Patients with a high IFN-1 gene expression signature treated with cenerimod 4 mg experienced a greater reduction in mSLEDAI-2K score at month 6 (−2.78) compared to placebo. Additionally, this subgroup exhibited a 24% higher SRI-4 response rate than the placebo group.
- Biomarker Insights: Cenerimod 4 mg significantly reduced levels of IFN-γ-associated proteins and IFN-1 protein and gene expression biomarkers after 6 months compared to placebo. These effects were more pronounced in the IFN-1 high subgroup, correlating with the stronger clinical response observed in these patients.
Safety Profile
Over the 12-month treatment and follow-up period, most adverse events (AEs) were mild to moderate. No serious adverse events (SAEs) related to cenerimod were reported. Cenerimod was well tolerated across all evaluated doses.
Publications and Access
The abstract of the publication in Lancet Rheumatology, titled “Cenerimod, a sphingosine-1-phosphate receptor modulator, versus placebo in patients with moderate-to-severe systemic lupus erythematosus (CARE): an international, double-blind, randomised, placebo-controlled, Phase 2 Trial,” is accessible online. The biomarker analysis published in Annals of the Rheumatic Diseases further characterized the immunomodulatory effects of cenerimod, adding valuable insights into its role in targeting key mechanisms underlying SLE.
Future Directions
The positive outcomes from the CARE study have set the stage for the Phase 3 OPUS program, which aims to further evaluate the efficacy, safety, and long-term benefits of cenerimod in a larger patient population. Viatris remains committed to advancing innovative treatments for SLE, addressing unmet needs, and improving the quality of life for individuals living with this complex autoimmune condition.
With its promising Phase 2b results and ongoing Phase 3 trials, cenerimod represents a potential breakthrough in SLE management, offering hope to patients and clinicians seeking more effective therapeutic options.
