#2-12E. Nanobody Breakthrough: Dual IL-17A/F Inhibition Achieves Robust Multi-Domain Control in Active PsA (Nat Med, 2025)

How can we optimize treatment strategies for Psoriatic Arthritis (PsA), a progressive, multi-domain disease where achieving Minimal Disease Activity (MDA) remains a challenge even with current biologics? This randomized Phase 2 trial, the ARGO study, evaluated sonelokimab (SLK)—a nanobody designed for high-affinity dual inhibition of IL-17A and IL-17F—in 207 patients with active PsA12. SLK 60mg and 120mg induction regimens achieved the primary endpoint of ACR50 at Week 12 significantly better than placebo (up to 46.5% vs. 20.0%). The most significant finding suggests that SLK’s smaller molecular weight and albumin-binding domain confer superior tissue penetration into traditionally hard-to-reach inflammatory sites, yielding robust multi-domain efficacy, including high rates of high-threshold composites like ACR70 + PASI 100. However, as a Phase 2 study, statistical power to assess specific disease domains like enthesitis and dactylitis was limited by the small number of affected patients at baseline. These encouraging results, showing sustained high disease control (up to 62% MDA at Week 24)1... across various subgroups, suggest SLK's unique structure offers a promising pathway for achieving comprehensive therapeutic goals in PsA practice.

Citation: Iain B. McInnes, Laura C. Coates, Philip J. Mease, et al. Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial. nature medicine. 2025. DOI: 10.1038/s41591-025-03971-6

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