Secukinumab Falls Short in Phase III SELUNE Trial
Key Takeaways
- In SELUNE, complete renal response at week 52 was lower with secukinumab than with placebo in lupus nephritis.
- Adverse event rates were broadly similar, no new or unexpected safety signals emerged overall.
SELUNE was a multicenter phase III randomized, placebo-controlled, double-blind core study planned for 104 weeks, followed by an open-label extension planned to 260 weeks. Adults aged 18 to 75 years with confirmed SLE, a documented history of at least 4 ACR criteria (or LN as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies), and active lupus nephritis were eligible for the secukinumab placebo comparison in active lupus nephritis.
The trial randomized 275 patients, with 137 assigned to secukinumab and 138 to placebo, using weekly dosing for four weeks and monthly maintenance thereafter alongside background standard care. Baseline characteristics were generally balanced, with a mean age of 33.6 years, 87.3% female participants, 48.4% with class IV disease without class V features, and a mean 3.1 years since lupus nephritis diagnosis. The primary endpoint in the core study was complete renal response at week 52.
Both the core study and the extension stopped early after a planned futility analysis found no clinically meaningful benefit of secukinumab over placebo. The final core analysis included 182 patients, with 91 in each group. Estimated mean week 52 response rates were 25.9% with secukinumab and 38.6% with placebo, for a difference of minus 12.7 percentage points with a 95% confidence interval from minus 26.3 to 0.9. No between-group differences were seen across prespecified secondary endpoints, including partial renal response, 24-hour urine protein-to-creatinine ratio, corticosteroid dose, time-to-response measures, first morning void UPCR of 0.5 mg/mg or less, and patient-reported outcomes. Partial renal response was 56.2% with secukinumab and 63.9% with placebo, and the primary objective was not met.
Treatment-emergent adverse events were comparable in the randomized phase and extension, occurring in 87.6% and 93.8% of secukinumab recipients and 89.1% and 100.0% of comparator groups. Serious adverse events in the core study occurred in 21.9% with secukinumab and 28.3% with placebo. Common events included upper respiratory tract infection, COVID-19, urinary tract infection, arthralgia, diarrhea, headache, and cough, and most were mild to moderate. One death occurred in each core-study group. In the secukinumab group, one death from meningitis was assessed by the investigator as related to study treatment and background immunosuppression, although the sponsor attributed it to background immunosuppressive treatment rather than study treatment. Fungal infections were numerically more frequent with secukinumab and were mainly Candida infections, with oral candidiasis the most common Candida infection. No major adverse cardiovascular events were reported with secukinumab. Only 31 patients contributed to the extension analysis, and extension efficacy was uninterpretable.