The IL-17A/F-targeting nanobody has delivered positive topline results across joints, skin, function, and minimal disease activity in biologic-naive patients, but the placebo comparison remains blinded.
Investigational IL-17A/IL-17F inhibitor sonelokimab has met its primary endpoint and all clinical secondary endpoints in a phase 3 psoriatic arthritis trial, with more than four in 10 biologic-naive patients achieving an ACR50 response after 16 weeks.
The investigational IL-17A and IL-17F inhibitor also produced responses across joint and skin disease, minimal disease activity, physical function, and patient-reported outcomes in the global IZAR-1 trial, according to topline results released by developer MoonLake Immunotherapeutics.
At week 16, 42.1% of patients receiving sonelokimab 60mg with induction achieved the primary endpoint of ACR50, representing at least a 50% improvement in American College of Rheumatology response criteria.
ACR20 was achieved by 66.5% of patients and 41.2% reached minimal disease activity. Among patients with concomitant psoriasis, 61% achieved PASI90.
Mean change from baseline on the Health Assessment Questionnaire Disability Index was -0.427, while the mean improvement in the SF-36 Physical Component Summary score was 6.54.
But an important piece of the efficacy picture is not yet available.
IZAR-1 remains blinded, and MoonLake has not released corresponding placebo response rates, treatment differences, confidence intervals, or detailed results from the other study arms.
The company said the restricted disclosure was consistent with an unblinding protocol defined with the US FDA, with comparative analyses against placebo and detailed treatment-arm data to remain blinded until completion of the phase 3 program.
That means the reported 42.1% ACR50 rate cannot yet be interpreted as the treatment effect attributable to sonelokimab, nor can the results support reliable indirect comparisons with approved PsA therapies.
Dr Jorge Santos da Silva, MoonLake founder and chief executive officer, said the results represented an important milestone and the company was particularly encouraged by efficacy across multiple clinically relevant endpoints.
“These data are also encouraging as they are consistent with what was previously observed in other IL-17A/F programs,” he said.
“This reinforces our conviction that sonelokimab has the potential to become a leading treatment option in PsA and further validate the broad potential of our Nanobody® platform in inflammatory disease.”
IZAR-1 is a global, randomised, double-blind phase 3 trial in biologic-naive adults with active PsA. Patients will remain in the study through week 52 to assess durability of efficacy and longer-term safety.
Unlike some pivotal PsA trials, IZAR-1 does not contain an active standard-of-care comparator. MoonLake said its phase 2 ARGO study had already provided an active-reference context through an adalimumab arm.
The phase 3 program also includes IZAR-2, which is investigating sonelokimab in patients with an inadequate response to TNF inhibitors. That study includes the IL-23 inhibitor risankizumab as an active reference arm and is expected to complete enrolment in the third quarter of 2026.
Sonelokimab is a humanised nanobody designed to neutralise IL-17A and IL-17F, binding both cytokines with similarly high affinity and inhibiting IL-17A/A and IL-17F/F homodimers as well as IL-17A/F heterodimers.
At around 40kDa, it is substantially smaller than conventional monoclonal antibodies, which are typically around 150kDa. Its developers hypothesise that the smaller molecule may penetrate inflamed tissues more effectively, which may be particularly relevant in PsA where inflammation occurs across synovium, skin, and entheses.
The phase 3 findings follow encouraging results from the 207-patient phase 2 ARGO trial, published in Nature Medicine in 2025.
That randomised, double-blind study compared several sonelokimab regimens with placebo and included adalimumab 40mg every two weeks as a reference arm, although it was not powered for statistical comparisons with adalimumab.
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ARGO compared several sonelokimab regimens with placebo and included adalimumab 40mg every two weeks as a reference arm, although it was not powered for statistical comparisons with adalimumab.
At week 12, ACR50 was achieved by 46.3% of patients receiving sonelokimab 60mg with induction and 46.5% receiving 120mg with induction, compared with 20% receiving placebo. The corresponding rate in the adalimumab reference group was 42.9%.
Responses continued to increase after the placebo-controlled period. By week 24, between 58.1% and 61.0% of patients originally randomised to sonelokimab had achieved ACR50, compared with 54.8% in the adalimumab group.
Skin responses were also strong. At week 12, PASI90 was achieved by 76.9% of patients receiving sonelokimab 60mg with induction and 59.3% receiving 120mg with induction, compared with 15.4% receiving placebo.
By week 24, ACR70 responses were seen in 39.0% to 41.9% of patients in the sonelokimab groups, compared with 35.7% in the adalimumab reference arm.
The skin results were similarly strong. At week 12, PASI90 was achieved by 76.9% of patients receiving sonelokimab 60mg with induction and 59.3% receiving 120mg with induction, compared with 15.4% of placebo-treated patients.
Complete skin clearance, measured by PASI100, was achieved by 37.5% to 57.7% of sonelokimab-treated patients at week 12 and by 59.4% to 63.0% at week 24.
The phase 2 study also examined whether patients could achieve disease control across several domains simultaneously.
Minimal disease activity was achieved by 43.9% of patients receiving the 60mg induction regimen at week 12, compared with 20% receiving placebo. By week 24, MDA rates reached 61.0% with the 60mg induction regimen and 51.2% with 120mg induction, compared with 45.2% in the adalimumab reference arm.
MoonLake said the blinded safety analysis from IZAR-1 was consistent with previous sonelokimab studies, with no new safety signals and a low dropout rate through week 16. Treatment-specific phase 3 safety rates have not yet been released.
In ARGO, treatment-emergent adverse events occurred in 45.1% of patients exposed to sonelokimab 60mg and 58.8% exposed to 120mg over 24 weeks, compared with 46.8% in the adalimumab group.
The most common events with sonelokimab were nasopharyngitis, upper respiratory tract infection, injection-site erythema, and headache. Four mild-to-moderate cases of oral candidiasis were recorded, while serious adverse events and discontinuations due to adverse events were uncommon.
The IZAR results also come as MoonLake advances sonelokimab across several immune-mediated inflammatory diseases. The company has completed phase 3 studies in hidradenitis suppurativa and is preparing a US biologics licence application for that indication, while PsA represents another potential major indication for the drug.
Sonelokimab remains investigational and is not approved for the treatment of PsA.
