Phase 3 Trial Confirms Nemolizumab’s Efficacy for Moderate to Severe Prurigo Nodularis

"Our findings validate the effectiveness of using nemolizumab to target interleukin-31 signaling in adults with moderate to severe PN," the researchers wrote in JAMA Dermatology. They revealed that nemolizumab monotherapy resulted in significant and clinically relevant improvements in the key signs and symptoms of PN.

Prurigo nodularis is a chronic skin condition marked by intensely itchy nodules, significantly impairing patients' quality of life. Nemolizumab's mode of action involves inhibiting interleukin-31 signaling, a key pathway in the inflammatory processes linked to PN. Therefore, Sonja Ständer, Center for Chronic Pruritus and Department for Dermatology, University Hospital Münster, Münster, Germany, and colleagues aimed to evaluate the effectiveness and incidence of adverse events in adults with moderate to severe PN treated with nemolizumab compared to those receiving a placebo.

For this purpose, the researchers conducted OLYMPIA 1, a multicenter, placebo-controlled phase 3 trial from August 2020 to March 2023, at 77 centers across 10 countries. It included adults with moderate to severe prurigo nodularis, defined by at least 20 nodules, an Investigator’s Global Assessment score of 3 or higher, and a Peak Pruritus Numerical Rating Scale of at least 7. Participants underwent screening, 24 weeks of treatment, and an 8-week follow-up. Patients were randomized 2:1 to receive weight-based nemolizumab doses or placebo every four weeks. Primary outcomes included itch relief and skin clearance by week 16.

The study led to the following findings:

• Among 286 patients (mean age 57.5 years, mean weight 85.0 kg, 58% female), 190 received nemolizumab, and 96 received placebo.
• At week 16, 58.4% of nemolizumab patients achieved itch response compared to 16.7% on placebo (difference: 40.1%).
• The investigator’s Global Assessment (IGA) success rate was 26.3% in nemolizumab patients versus 7.3% on placebo (difference: 14.6%).
• At week 24, 58.3% of nemolizumab patients achieved itch response versus 20.4% on placebo (difference: 38.7%), and IGA success was 30.5% versus 9.4% (difference: 19.2%).
• Adverse events, mostly mild to moderate, occurred in 71.7% of nemolizumab patients and 65.3% of placebo patients.

In the phase 3 trial, nemolizumab monotherapy showed rapid and sustained improvements in key signs (skin lesions) and symptoms (itch and sleep issues) of PN. Headache and eczema were more common with nemolizumab than with a placebo. The findings align with previous studies.

The researchers highlighted that the 24-week trial excluded patients with uncontrolled systemic conditions and predominantly included White participants, which may limit the generalizability of the findings.

"Given the chronic nature of prurigo nodularis, longer-duration studies are necessary, and a 184-week open-label extension study is currently underway," they wrote.

Reference:

Ständer S, Yosipovitch G, Legat FJ, et al. Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis: The OLYMPIA 1 Randomized Clinical Phase 3 Trial. JAMA Dermatol. Published online November 27, 2024. doi:10.1001/jamadermatol.2024.4796