Vixarelimab Demonstrates Rapid, Sustained Clinical Benefits in Prurigo Nodularis

Vixarelimab therapy demonstrated rapid, sustained, dose-dependent clinical benefits among individuals with prurigo nodularis, according to new findings, as well as a favorable safety profile.1

The drug was designed as a first-in-class human monoclonal antibody for patients with prurigo nodularis, targeting oncostatin M (OSM) β and inhibiting both OSM and interleukin (IL)-31 signaling pathways. This analysis, authored by investigators such as Sonja Ständer, MD, of Münster University Hospital, was conducted to look at the medication’s long-term efficacy and safety as well as pharmacokinetic profiles of monthly vixarelimab doses.

Ständer et al highlighted prior phase 2a data in which reduction of pruritus was observed among prurigo nodularis patients, along with attainment of clear or almost clear skin in one-third of subjects on the drug by Week 8.2

“Here, we report results from the phase 2b trial evaluating the efficacy, safety, tolerability, and pharmacokinetics of monthly dosed vixarelimab in participants with [prurigo nodularis] with moderate to severe pruritus over 16 weeks,” Ständer and coauthors wrote.1

Study Design and Findings

The investigative team conducted this analysis in the period between December 2020 - August 2023. They included a 4-week phase for screening, a 16-week randomized double-blind treatment phase, and a subsequent 36-week open-label extension period. The study resulted in a total potential participation time of approximately 56 weeks per patient.

Participants were involved at 72 clinical sites found around Canada, the US, Europe, and Asia. Adults in the age range of 18 - 80 years with a verified diagnosis of prurigo nodularis lasting 6 months at minimum. Those taking part as subjects were also required to have moderate to severe itch at both screening and baseline. Moderate to severe itch was defined by Ständer and colleagues as the presence of at least 20 pruritic nodules measuring 0.5 to 2 cm distributed across a minimum of 2 distinct regions of the body.

Severe itch was characterized by a Worst Itch Numeric Rating Scale (WI-NRS) score of 7 or higher at screening and an average weekly WI-NRS score of at least 7 during the week before randomization, based on a minimum of 5 daily entries recorded in an electronic diary. In addition, participants were required to have a prurigo nodularis Investigator Global Assessment score of 3 or greater, indicating at least moderate disease severity on a 0-to-4 scale.

In the double-blind phase lasting 16 weeks, those in the study were randomly assigned by Ständer et al to be subcutaneously treated with doses of vixarelimab at 540 mg, 360 mg, or 120 mg, or matching placebo. The drug was administered on an every-4-week basis. During the open-label extension period, all involved were given 360 mg vixarelimab every 2 weeks for 36 weeks.

The study's primary and key secondary efficacy measures evaluated in the study included the proportion of subjects attaining at least 4-point reduction in WI-NRS by the 16-week mark, the percentage shift seen from the point of baseline in WI-NRS at the same time point, and the proportion attaining a 0 or 1 score on the prurigo nodularis Investigator Global Assessment at the same point.

189 of the 190 people who were randomized by Ständer and coauthors were given at least a single medication dose. These individuals included 141 and 48 assigned to vixarelimab or placebo, respectively. The study was made up of 60.3% women and 39.7% men. The participants' mean age was 55.4 years. Each vixarelimab dose group included 47 individuals. Treatment with vixarelimab at the 16-week mark led to significantly increased mean WI-NRS score reductions compared with placebo across all dosing cohorts.

Reductions were shown by the investigators to be as follows:

• −56.2% among those in the high-dose arm
• −51.0% among those in the mid-dose arm
• −33.0% among those the low-dose arm
• −14.5% in the placebo arm.

At least a 4-point reduction in WI-NRS scores was seen by Ständer et al in 31 66.0% of those on high-doses of the drug, 61.7% of those in the mid-dose arm, and 29.8% in the low-dose arm. This was compared with 16.7% in the placebo arm of the study. Attainment of Investigator Global Assessment scores of 0 or 1 was also more commonly identified among participants treated with vixarelimab. Specific percentages were as follows:

• 38.3% of those in the high-dose cohort
• 29.8% of those in the mid-dose cohort
• 14.9% of those in the low-dose cohort
• 10.4% of those in the placebo cohort

Additionally, the drug's safety profile was highlighted by Ständer and colleagues following the analysis. There were no fatal events or serious treatment-emergent adverse events (TEASs) attributed to the medication reported in the study.

“Overall, mild TEAEs were observed with vixarelimab, with no fatal or serious drug-related TEAEs reported and no serious treatment-related TEAEs observed during the DB period,” the investigative team concluded.1 “These results highlight the favorable benefit-risk profile of vixarelimab.”

References

1. Ständer S, Yosipovitch G, Sofen H, et al. Vixarelimab in Patients With Prurigo Nodularis: A Randomized Clinical Trial. JAMA Dermatol. Published online December 17, 2025. doi:10.1001/jamadermatol.2025.4950.

2. Sofen H, Bissonnette R, Paolini JF, et al. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate-to-severe prurigo nodularis: a randomised, double-blind, placebo-controlled, phase 2a study. EClinicalMedicine. 2023 Feb 3;57:101826. doi: 10.1016/j.eclinm.2023.101826. PMID: 36816342; PMCID: PMC9932343.