Galderma has announced the publication of full results from its Phase III OLYMPIA 1 trial in JAMA Dermatology, demonstrating that nemolizumab monotherapy significantly improved the core symptoms of prurigo nodularis in adult patients with moderate-to-severe disease.
The 24-week randomized, double-blind, placebo-controlled study enrolled 286 adult patients with moderate-to-severe prurigo nodularis. Results showed that nemolizumab met both primary endpoints and all key secondary endpoints, providing rapid and clinically meaningful improvements in itch, skin lesions, and sleep disturbance compared to placebo.
Significant Improvements in Primary Endpoints
After 16 weeks of treatment, nemolizumab demonstrated superior efficacy over placebo in both primary endpoints:
- 58.4% of nemolizumab-treated patients achieved at least a four-point improvement in itch intensity, as measured by the peak-pruritus numerical rating scale (PP-NRS), compared to only 16.7% in the placebo group (P<0.001)
- 26.3% of patients receiving nemolizumab reached clearance or almost-clearance of skin lesions, as assessed by the investigator's global assessment (IGA score of 0 or 1 and a ≥2-point improvement from baseline), versus 7.3% in the placebo group (P<0.01)
Rapid Response on Key Symptoms
The trial also demonstrated rapid onset of action, with significant improvements observed as early as Week 4:
- More than six times as many nemolizumab-treated patients achieved itch response compared to placebo (41.1% vs 6.3%; P<0.001)
- More than twenty times as many nemolizumab-treated patients achieved a PP-NRS score of less than two (indicating an itch-free or nearly itch-free state) compared to placebo (21.6% vs 1.0%; P<0.001)
- Almost six times as many nemolizumab-treated patients demonstrated a four-point improvement in sleep disturbance compared to placebo (31.1% vs 5.2%; P<0.001)
These improvements continued through Week 16, with 34.2% of nemolizumab-treated patients achieving a PP-NRS score of less than two (vs 4.2% for placebo; P<0.001) and 50.0% showing significant sleep improvement (vs 11.5% for placebo; P<0.001).
Professor Sonja Ständer, lead investigator and Professor of Dermatology at University Hospital Münster, Germany, commented: "The full phase III OLYMPIA 1 trial results add to the extensive body of evidence supporting nemolizumab's potential to significantly and safely improve some of the most debilitating symptoms for people with prurigo nodularis – chronic itch, skin nodules, and poor sleep quality – which can be all consuming and have a knock-on effect on patients' overall quality of life and mental health."
Mechanism of Action and Disease Impact
Nemolizumab is a first-in-class monoclonal antibody that specifically targets IL-31 receptor alpha, inhibiting the signaling of IL-31, a neuroimmune cytokine that drives multiple disease mechanisms in prurigo nodularis.
Prurigo nodularis is a chronic, debilitating neuroimmune skin disease characterized by intense itch and thick skin nodules covering large body areas. It affects an estimated 181,000 people in the United States and significantly impacts quality of life, with the majority of patients reporting that persistent itch negatively affects their daily functioning and causes significant sleep disturbance.
Regulatory Status and Future Directions
Based on data from the OLYMPIA clinical trial program, which includes both the OLYMPIA 1 and OLYMPIA 2 trials, nemolizumab received approval from the U.S. Food and Drug Administration for the treatment of adults with prurigo nodularis under the brand name Nemluvio® in August 2024. This makes it the first approved monoclonal antibody specifically inhibiting the signaling of IL-31.
Dr. Baldo Scassellati Sforzolini, Global Head of R&D at Galderma, stated: "These results, alongside the OLYMPIA 2 trial data, formed the basis of nemolizumab's recent U.S. Food and Drug Administration approval for the treatment of adults with prurigo nodularis. They demonstrate the potential of this treatment to rapidly and significantly provide relief from the most burdensome symptom for people with prurigo nodularis – itch. We are committed to bringing this treatment option to patients in other parts of the world as soon as possible."
Galderma has marketing authorization applications for nemolizumab in both prurigo nodularis and atopic dermatitis under review by multiple additional regulatory authorities, including the European Medicines Agency and via the Access Consortium framework in countries such as Australia, Singapore, and Switzerland, as well as Canada, Brazil, and South Korea.
The U.S. FDA has also accepted for review Galderma's Biologics License Application for nemolizumab for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis, with a decision expected by the end of the year.
The OLYMPIA trial program is the largest Phase III program in prurigo nodularis completed to date and the only one to include an open-label, long-term extension study.
Safety Profile
In the OLYMPIA 1 trial, nemolizumab was well-tolerated, with a safety profile generally consistent with previous studies. During the treatment period, 71.7% of patients receiving nemolizumab experienced at least one adverse event, compared to 65.3% of patients receiving placebo. The most common events in the nemolizumab group were mild to moderate, including headache and eczema.
The publication of these results in JAMA Dermatology represents an important milestone in addressing the significant unmet need for effective treatments for prurigo nodularis, a condition that has historically had limited therapeutic options.
