Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Medicine, https://doi.org/10.1038/s41591-025-03971-6 Dr. Iain B. McInnes et al.
Points
- This Phase 2 randomized, double-blind trial assessed the efficacy and safety of sonelokimab (SLK), an IL-17A/IL-17F-inhibiting nanobody, in 207 patients suffering from active psoriatic arthritis.
- The primary endpoint of ACR50 at Week 12 was met, with SLK 60-mg WI and 120-mg WI achieving response rates of 46.3% and 46.5% respectively, versus 20.0% for placebo.
- SLK demonstrated significant superiority on key secondary endpoints, including ACR20 at 78.0% and 72.1%, and PASI90 at 76.9% and 59.3% for the induction groups compared to the placebo arm.
- High-threshold composite endpoints at Week 24, such as minimal disease activity, were robustly achieved by up to 61% of patients in the 60-mg WI group.
- The nanobody was well-tolerated, with the most common adverse events being mild upper respiratory infections and nasopharyngitis, and 4 cases of mild to moderate oral candidiasis reported.
Summary
This randomized, double-blind, placebo (PBO)-controlled Phase 2 trial evaluated the efficacy and safety of sonelokimab (SLK), an anti-IL-17A/IL-17F nanobody, in 207 patients with active Psoriatic Arthritis (PsA). Patients were randomized to SLK 120-mg or 60-mg every 4 weeks (Q4W; both with induction [WI]), SLK 60-mg Q4W (no induction), PBO, or adalimumab (reference arm). The primary endpoint was the American College of Rheumatology (ACR50) response at Week 12.
The primary endpoint was met for both SLK induction regimens. The SLK $\mathbf{60\text{-mg WI}$ group achieved an ACR50 rate of 46.3% (19/41), yielding an odds ratio (OR) of 3.6 (95% confidence interval [CI]=1.3–9.9; P<0.05) compared to the PBO rate of 20.0% (8/40). The SLK $\mathbf{120\text{-mg WI}$ group achieved an ACR50 rate of 46.5% (20/43), with an OR of 4.0 (95% CI =1.4–11.3; P<0.01) versus PBO. SLK also demonstrated significant superiority across key secondary endpoints. For ACR20 at Week 12, the 60-mg WI and 120-mg WI groups achieved responses of 78.0% (32/41; P<0.001) and 72.1% (31/43; P=0.002), respectively, versus the PBO rate of 37.5% (15/40). Psoriasis Area and Severity Index (PASI90) at Week 12 was also significantly higher for SLK, with 76.9% (20/26; P<0.001) and 59.3% (16/27; P=0.003) for the 60-mg WI and 120-mg WI groups, respectively, versus 15.4% (4/26) for PBO.
Sonelokimab was well-tolerated across both dosing groups. The most common treatment-emergent adverse events were nasopharyngitis (60 mg=6.1%; 120 mg=5.2%) and upper respiratory tract infection (60 mg=6.1%; 120 mg=4.1%). Four cases of mild to moderate oral candidiasis were reported (60 mg=2.4%; 120 mg=2.1%). Robust responses were further observed at Week 24 for high-threshold endpoints, including minimal disease activity, achieved by up to 61% (25/41) in the 60-mg WI group.
Link to the article: https://www.nature.com/articles/s41591-025-03971-6
References
McInnes, I. B., Coates, L. C., Mease, P. J., Ogdie, A., Kavanaugh, A., Eder, L., Schett, G., Kivitz, A., McGonagle, D., Brennan, N., Godwood, A., Cullen, E., Reich, K., Ritchlin, C. T., & Merola, J. F. (2025). Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: A randomized, placebo-controlled phase 2 trial. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-025-03971-6
