Dual-Targeting Nanobody Sonelokimab Shows Promise in Psoriatic Arthritis Phase 2 Trial

A novel nanobody therapy targeting dual inflammatory pathways has shown encouraging results in treating psoriatic arthritis (PsA), a complex and disabling autoimmune disease. The investigational agent, sonelokimab, achieved significant improvements in joint and skin symptoms in a phase 2 clinical trial, offering a potential new option for patients who struggle to reach remission with current biologics.

The global, randomized, placebo-controlled ARGO study enrolled over 200 adults with active PsA to evaluate sonelokimab—a small, antibody-derived molecule that simultaneously inhibits both interleukin-17A (IL-17A) and interleukin-17F. These two cytokines are increasingly recognized as key drivers of the inflammatory processes underlying PsA, particularly in difficult-to-reach tissue sites such as the entheses and synovial joints.

Participants were randomized to receive one of three sonelokimab regimens, placebo, or adalimumab, a widely used tumor necrosis factor inhibitor that served as a reference arm. The primary endpoint—achievement of a 50% improvement in joint symptoms (ACR50) at week 12—was met in both induction-dose sonelokimab arms. Nearly 47% of patients receiving either 60 mg or 120 mg doses with induction achieved ACR50, compared to just 20% in the placebo group. The response was similar to the 42.9% ACR50 rate observed with adalimumab.

Key secondary endpoints reinforced the drug’s efficacy. At week 12, over 70% of patients on sonelokimab achieved ACR20, a benchmark of clinical improvement. For patients with psoriasis affecting at least 3% of their body surface area, the skin clearance rate (PASI 90) reached 77% in the 60 mg induction group, and 59% in the 120 mg group—substantially higher than the 15% clearance rate among those receiving placebo. Complete skin clearance (PASI 100) at week 24 was observed in up to 63% of patients.

The drug also demonstrated strong performance on composite endpoints. Up to 48% of patients achieved simultaneous ACR70 and PASI 100 responses by week 24, and 61% reached minimal disease activity—a stringent target rarely achieved in real-world settings. Improvements extended to difficult domains such as nail psoriasis, enthesitis, and axial symptoms, though the study’s size limited statistical conclusions in those areas.

Notably, sonelokimab appeared equally effective across subgroups typically associated with reduced response to therapy, including female patients, those with prior biologic exposure, and individuals weighing over 100 kg. Patients with moderate-to-severe psoriasis at baseline were especially likely to achieve complete skin clearance in the 120 mg induction group.

Sonelokimab’s structural design may offer a biological edge. Unlike conventional monoclonal antibodies, which are larger and may struggle to reach inflamed joint tissues, sonelokimab is a 40 kDa nanobody engineered for deeper tissue penetration. It binds both IL-17A and IL-17F with high affinity and includes an albumin-binding domain that prolongs its half-life and concentrates the drug in sites of chronic inflammation.

The safety profile was consistent with previous IL-17 inhibitors. Common adverse events included mild nasopharyngitis, upper respiratory infections, injection site reactions, and headache. Four cases of mild-to-moderate oral candidiasis were reported, and there were no instances of inflammatory bowel disease, liver toxicity, or suicidal ideation—concerns previously noted with some IL-17-targeted therapies.

While the trial was not powered to compare directly against adalimumab, sonelokimab’s numerically higher response rates across joint and skin domains suggest potential competitive advantages. The findings set the stage for two ongoing phase 3 trials—IZAR-1 in biologic-naive patients and IZAR-2 in those with prior TNF inhibitor failure—that aim to further establish the drug’s clinical utility.

If confirmed, sonelokimab could represent a new frontier in PsA treatment, combining dual-cytokine targeting with nanobody engineering to reach inflamed tissues more effectively. As clinicians continue to grapple with the heterogeneity of PsA, therapies that offer both broad efficacy and deep tissue penetration may redefine treatment goals for this challenging disease.