Sonelokimab shows potential in treating palmoplantar pustulosis in LEDA trial

In the phase 2 LEDA trial, sonelokimab reduced disease severity by a mean of 64%, with 40% of participants with moderate-to-severe palmoplantar pustulosis achieving clear or almost clear skin at Week 16

Palmoplantar pustulosis (PPP) has a complex pathophysiology, and no targeted treatments are currently approved in the EU or USA. T helper 17 (Th17) signaling may play an important role, with interleukin-17A (IL-17A) and IL-17F promoting neutrophil recruitment and excessive keratinocyte proliferation. Sonelokimab is an investigational nanobody, approximately 40 kDa in size, that binds both cytokines with similarly high affinity.¹

Results from the open-label phase 2 LEDA trial (EUCT 2024-513305-32-00) were presented at the 2026 European Academy of Dermatology and Venereology (EADV) Congress. The trial evaluated sonelokimab’s efficacy, safety, and effects on disease-related biological pathways in adults with PPP.1 Following the presentation, we were delighted to speak with study investigator and presenter Dr Nina Magnolo (University Hospital Münster, Münster, Germany) about sonelokimab’s mechanism of action, the trial findings, and their potential implications for clinical practice and people living with PPP.

Q. What is sonelokimab, and how is it thought to work in treating PPP?

Sonelokimab is an investigational nanobody that inhibits IL-17A and IL-17F.

Nanobodies are small antigen-binding units derived from heavy-chain-only antibodies, which occur naturally in camelids. Sonelokimab consists of three linked binding units: two target IL-17A and IL-17F, while the third binds to albumin to extend its half-life. By inhibiting these inflammatory cytokines, it aims to reduce inflammation.

Q. Could you tell us about the LEDA trial and what it revealed about sonelokimab in PPP?

The trial enrolled 32 patients with moderate-to-severe PPP, defined by a Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) score >12 at Baseline. Patients received sonelokimab 120 mg every 2 weeks through Week 8, followed by a final injection at Week 12. A total of 28 patients completed the study through Week 16.

The primary endpoint was the percentage change in PPPASI from Baseline to Week 16. At this time point, a mean reduction of 64% was observed. In addition, four in 10 patients achieved clear or almost clear skin, defined by a Palmoplantar Pustulosis Investigator’s Global Assessment (PPP-IGA) score of zero or one. [Significant improvements in quality of life, measured using the Dermatology Life Quality Index (DLQI), were also recorded from Week 2 onwards, with a five-point reduction at Week 2 (p<0.001). At Week 16, 44% of patients achieved a DLQI score of zero or one.]

Secondary endpoints included biomarker analyses, which showed a significant reduction in markers such as IL-19 as early as Week 4. We also identified pathways associated with disease activity at Baseline and with treatment response, including those related to the innate immune system and IL-17 signaling.

No new safety signals were identified, and treatment was well tolerated. Candida infections were observed, consistent with the known safety profile of IL-17A and IL-17F blockade, and no severe adverse events were reported.

Q. What are the next steps in evaluating the potential of sonelokimab in PPP?

A phase 3 trial is already planned and is expected to begin this year, and we are pleased to be participating in this next stage of the research.

There remains a substantial unmet need, as no biologic therapies are approved by the FDA or EMA for PPP. The condition can profoundly affect patients’ quality of life, with pustules on the palms and soles causing considerable suffering and, for some, preventing them from working. Making new therapies available to these patients is therefore a priority.

Note: This transcript has been lightly edited to ensure clarity.

Reference

1. Magnolo N, Wilsmann-Theis D, Mößner R, et al. Sonelokimab, a novel IL-17A- and IL-17F-inhibiting nanobody, in moderate-to-severe palmoplantar pustulosis: Efficacy, safety, and translational results from the open-label phase 2 LEDA trial. Presented at: EADV Congress 2026, Vienna, Austria, 2 October, 2026. Abstr#1819.