IZAR-1: Sonelokimab Meets Phase 3 End Points for PsA

This article originally appeared on our sister site, RheumatologyLive.

Sonelokimab (60 mg with induction) met the primary end point of American College of Rheumatology 50% response (ACR50) at week 16 in biologic-naive adults with active psoriatic arthritis (PsA), according to topline results from the phase 3 IZAR-1 trial (NCT06641076) announced by MoonLake Immunotherapeutics.¹

IZAR-1 is 1 of 2 registrational, global, randomized, double-blind, placebo-controlled phase 3 trials, alongside IZAR-2, evaluating sonelokimab, an IL-17A/F-inhibiting nanobody, across a combined enrollment of approximately 1500 adults with active PsA.¹ IZAR-1 enrolled biologic-naive patients and includes an evaluation of radiographic progression, while IZAR-2 is enrolling patients with an inadequate response to tumor necrosis factor (TNF) inhibitors and includes a risankizumab active reference arm.¹

“The positive topline results from IZAR-1 represent an important milestone for MoonLake and, more importantly, for patients living with psoriatic arthritis,” said Jorge Santos da Silva, PhD, founder and chief executive officer of MoonLake Immunotherapeutics. “We are particularly encouraged by the strong efficacy observed across multiple clinically relevant end points simultaneously, which has been our focus. These data are also encouraging as they are consistent with what was previously observed in other IL-17A/F programs.”¹

What were the primary and secondary end point results in IZAR-1?

The primary end point of ACR50 at week 16 was met with a response rate of 42.1% among patients receiving sonelokimab 60 mg with induction, a statistically significant improvement over placebo.¹ Across key secondary end points, 66.5% of patients achieved an ACR20 response and 41.2% achieved minimal disease activity (MDA) at week 16.¹ Among patients with concomitant skin involvement, 61% achieved a 90% improvement in Psoriasis Area and Severity Index score.¹

Sonelokimab also produced meaningful, statistically significant improvements in patient-reported outcomes and physical function, including the Health Assessment Questionnaire Disability Index and the Short Form-36 Physical Component Summary score.¹ The company said the results support a broad multidomain efficacy profile of sonelokimab spanning musculoskeletal symptoms, skin disease, and physical function in PsA.¹

What are next steps for the IZAR program?

The blinded safety analysis of IZAR-1 suggested a profile consistent with prior sonelokimab studies, with no new safety signals identified.¹ The trial's dropout rate through week 16 was low and in line with other PsA trials.¹ IZAR-1 remains blinded and will continue through week 52, with a full readout expected in the first half of 2027, while IZAR-2, conducted in patients with an inadequate response to TNF inhibitors, is expected to complete enrollment in the third quarter of 2026.¹

The IZAR-1 results build on earlier phase 2 ARGO trial data, in which approximately 60% of sonelokimab-treated patients achieved ACR50 and MDA responses at week 24.¹ Sonelokimab's lead indication remains hidradenitis suppurativa, and the company said the IZAR-1 results set a path for the agent to enter PsA, which it characterized as another multibillion-dollar indication.¹

The therapy is also being evaluated for active axial spondyloarthritis (axSpA) in the phase 2 S-OLARIS study, data from which RheumatologyLive previously discussed with investigator Xenofon Baraliakos, MD, medical director of the Rheumazentrum Ruhrgebiet and professor of internal medicine and Rheumatology at Ruhr University Bochum in Herne, Germany, and current president of European Alliance of Associations for Rheumatology, at its annual meeting.

"The surprising finding was the clear message that osteoblastic activity is being decreased…we have had some first data on TNF blockers on that topic, but here we see this clearly in a prospective manner," Baraliakos said. "The high numbers need to be confirmed in a placebo-controlled trial, which we are obviously looking forward to conducting."

References

1. MoonLake Immunotherapeutics. MoonLake announces positive topline results from the phase 3 IZAR-1 trial of sonelokimab in psoriatic arthritis demonstrating significant improvements across all clinical endpoints, and reports second quarter 2026 financial results. News release. August 10, 2026. Accessed August 10, 2026. https://www.globenewswire.com/news-release/2026/08/10/3341679/0/en/moonlake-announces-positive-topline-results-from-the-phase-3-izar-1-trial-of-sonelokimab-in-psoriatic-arthritis-demonstrating-significant-improvements-across-all-clinical-endpoints.html
2. A study to learn about the effects of sonelokimab in adults with active psoriatic arthritis who have not been treated with a biologic before (IZAR-1). ClinicalTrials.gov. Accessed August 10, 2026. https://clinicaltrials.gov/study/NCT06641076