Sonelokimab Demonstrates Psoriatic Arthritis Improvements Over Placebo

Sonelokimab substantially improved signs and symptoms of psoriatic arthritis (PsA), meeting the primary endpoint of American College of Rheumatology (ACR) 50 response at week 12 compared to placebo in a phase 2 trial.1

“While IL-17A and IL-17F dual blockade shows substantial promise, further optimization may be able to maximize disease control. One limitation with current biologics may be the size of the therapeutic immunoglobulin G1 antibodies (typically around 150 kDa) that block inflammatory signaling. Delivery of mAbs into even the typically well-vascularized synovial joints is subject to size-dependent restrictions, and antibody concentration in synovial fluid is substantially less than in plasma. Although few studies have investigated antibody access across PsA tissue types, access to less vascular tissues such as the entheses may be further restricted, potentially limiting efficacy in low-bioavailability tissues,” study investigator Iain B. McInnes, PhD, College of Medical Veterinary & Life Sciences, University of Glasgow, and colleagues wrote.1

Sonelokimab is a nanobody that binds with a similarly high affinity to IL-17A and IL-17F, inhibiting all dimers. It was evaluated in a phase 2 randomized, double-blind, placebo-controlled trial involving 207 participants with active PsA randomized to sonelokimab 120-mg (n = 43) or 60-mg (n = 41) every 4 weeks (Q4W; both with induction [WI]), or to 60-mg Q4W with no induction [NI], placebo (n = 40) or adalimumab (reference arm). After 12 weeks, all patients receiving placebo switched to sonelokimab 120-mg NI until the end of study at week 24.

McInnes and colleagues found that, compared to 20% in the placebo group (n = 8), 46.3% of the 60 mg WI group (n = 19; OR, 3.6; 95% CI, 1.3-9.9; P <.05) and 46.5% of the 120 mg WI group (n = 20; OR, 4.0; 95% CI, 1.4-11.3; P <.01) met the primary endpoint of ACR50 response at week 12.The 120 mg NI group also met the primary endpoint.1

Sonelokimab further demonstrated efficacy on the key secondary endpoint of ACR20 in the 60-mg WI group (78.0%; n = 32; P <.001) and 120-mg WI group (72.1%; n = 31; P = .002) compared to placebo (37.5%; n = 15). Another secondary endpoint improved was Psoriasis Area and Severity Index (PASI) 90 at week 12 in the 60-mg WI group (76.9%; n = 20; P <.001) and 120-mg WI group (59.3%; n = 16/; P = .003) compared to placebo (15.4%; n = 4).1

Other endpoints explored were ACR70 + PASI 100 (exploratory) and minimal disease activity (secondary); these were achieved by up to 48% (n = 13/27 in 120-mg WI) and 61% (n = 25/41 in 60-mg WI), respectively. In terms of safety, sonelokimab was well-tolerated, with the most common treatment-emergent adverse events being nasopharyngitis (60 mg = 6.1%; 120 mg = 5.2%), upper respiratory tract infection (60 mg = 6.1%; 120 mg = 4.1%), injection-site erythema (60 mg = 3.7%; 120 mg = 3.1%) and headache (60 mg = 2.4%; 120 mg = 4.1%). There were also 4 cases of mild to moderate oral candidiasis occurred (60 mg = 2.4%; 120 mg = 2.1%).1

“In conclusion, this phase 2 study demonstrated that SLK yielded robust ACR50 responses compared with PBO at week 12. Highly encouraging response rates were also observed for higher threshold outcomes, such as ACR70 and PASI 100, as well as for multidomain measures of efficacy across different disease domains. SLK was well-tolerated, with a safety profile consistent with the inhibition of the IL-17 cytokine family, as observed in previous studies in plaque psoriasis and hidradenitis suppurativa,” McInnes and colleagues wrote.1 “The overall study results warrant further exploration of SLK in 2 ongoing phase 3 trials, the IZAR-1 study (NCT06641076) in patients with biologic-naive PsA, and the IZAR-2 study (NCT06641089) in patients with PsA and prior inadequate response or intolerance to biologic TNF inhibitors, to establish the potential of SLK as a future treatment for PsA.”

Notably, MoonLake Immunotherapeutics recently also shared mixed data on sonelokimab from the phase 3 VELA-1 and VELA-2 trials of its registrational global program in patients with moderate-to-severe hidradenitis suppurativa (HS), with only VELA-1 meeting the primary endpoint of Hidradenitis Suppurativa Clinical Response (HiSCR) 75, although VELA-2 did demonstrate statistical significance on its endpoint after additional prespecified analyses.2

References

1. McInnes, I.B., Coates, L.C., Mease, P.J. et al. Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial. Nat Med (2025). Published online October 6, 2025. doi: 10.1038/s41591-025-03971-6

2. Smith T. Phase 3 VELA Study Findings Suggest Sonelokimab Effective for HS. HCPLive. Article. September 29, 2025. https://www.hcplive.com/view/phase-3-vela-study-findings-suggest-sonelokimab-effective-hs