Incyte's ruxolitinib cream 1.5% (Opzelura) has demonstrated significant efficacy in treating prurigo nodularis (PN) in the first-ever Phase 3 clinical trials evaluating a topical therapy for this challenging skin condition. The results were presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.
The pivotal Phase 3 TRuE-PN clinical trial program, consisting of the TRuE-PN1 and TRuE-PN2 studies, evaluated twice-daily application of ruxolitinib cream in adult patients with prurigo nodularis, a chronic inflammatory skin disease characterized by intensely itchy nodules on the arms, legs, and trunk.
TRuE-PN1 Shows Significant Improvements in Itch and Lesions
The TRuE-PN1 study met its primary endpoint, with 44.6% of patients achieving a ≥4-point reduction in itch (Worst-Itch Numeric Rating Scale) at week 12, compared to 20.6% in the vehicle control group (P=0.0003). Notably, significant itch improvements were observed as early as day 7 (22.4% vs 8.0%; P=0.0064).
The study also met all key secondary endpoints. Significantly more patients who applied ruxolitinib cream versus vehicle control achieved an Investigator's Global Assessment for Stage of Chronic Prurigo Treatment Success (IGA-CPG-S-TS) at Week 12 (15.8% vs 3.9%; P=0.0048). Additionally, 11.9% of patients in the treatment group achieved overall treatment success compared to 2.9% in the control group (P=0.0164).
"This is the first study ever conducted for a topical agent for the treatment of prurigo nodularis. So really opening up avenues for the development and treatment. We're very excited about this for our patients," said Shawn Kwatra, MD, FAAD, Joseph W. Burnett Endowed Professor and Chair of Dermatology at the University of Maryland School of Medicine and Chief of Service Dermatology at the University of Maryland Medical Center.
TRuE-PN2 Results Show Positive Trends
The TRuE-PN2 study yielded similar findings, with approximately 40% of patients achieving a 4-point itch reduction. While the primary endpoint was in favor of ruxolitinib cream versus vehicle, it did not reach statistical significance due to a higher placebo response. However, the study demonstrated strong positive trends across all key secondary endpoints, particularly for IGA-CPG-S-TS at Week 12 and WI-NRS4 at Day 7 (nominal P-value <0.05 for both).
Safety Profile Consistent with Previous Data
The overall safety profile of ruxolitinib cream in the TRuE-PN clinical trial program was consistent with previous data, and no new safety signals were observed. This is particularly important for a medication targeting a chronic condition that requires ongoing management.
Addressing an Unmet Medical Need
Prurigo nodularis affects approximately 200,000 individuals in the U.S. and is most common among those 40-69 years old. The condition significantly impacts patients' quality of life, particularly due to intense itching that disrupts sleep and daily activities.
"PN is a challenging condition characterized by intensely itchy nodules that significantly impact patients' quality of life," said Jim Lee, MD, PhD, Group Vice President, Inflammation and Autoimmunity at Incyte. "These positive results display improvement in itch reduction and skin clearance, reinforcing the potential of ruxolitinib cream to become an effective topical treatment option that will help people living with PN."
Potential New Treatment Option
Currently, ruxolitinib cream 1.5% (Opzelura) is FDA-approved for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older and for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older.
The findings from the TRuE-PN1 and TRuE-PN2 studies will inform planned discussions with regulatory authorities to determine next steps for potential approval in prurigo nodularis. If approved, ruxolitinib cream would represent a significant advancement in the treatment landscape for PN, offering a non-systemic option that addresses both pruritus and lesion resolution.
Study Design
The TRuE-PN clinical trials enrolled approximately 180 patients each (age ≥18 years) diagnosed with PN. The studies included a 12-week double-blind, vehicle-controlled treatment period, followed by a 40-week open-label extension and 30-day safety follow-up.
Eligible patients had ≥6 pruriginous lesions on ≥2 different body areas at screening and baseline, with a treatment area <20% body surface area (BSA), an IGA-CPG-S score of ≥2 at screening and baseline, and a baseline PN-related WI-NRS score ≥7.
As the first topical JAK inhibitor evaluated for prurigo nodularis, ruxolitinib cream represents a potential breakthrough in addressing this challenging skin condition that has limited treatment options.
