Twice-daily ruxolitinib cream 1.5% (Opzelura, Incyte) met all primary and key secondary endpoints in a Phase 3 trial of adults with prurigo nodularis (PN).

The research was presented as a late-breaker at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, FL.

The Phase 3 TRuE-PN clinical trial program comprises TRuE-PN1 and TRuE-PN2 studies, which evaluate the safety and efficacy of twice-daily ruxolitinib cream 1.5% a topical JAK1/2 inhibitor in adult patients (≥18 years) with PN.

The TRuE-PN1 study met its primary endpoint, demonstrating that significantly more PN patients who applied ruxolitinib cream 1.5% vs. vehicle control achieved a ≥4-point improvement from baseline in Worst-Itch Numeric Rating Scale (WI-NRS4) at Week 12 (44.6% vs. 20.6%, respectively). Significant itch improvements were observed with ruxolitinib cream at 1.5% vs. vehicle control on Day 7 (22.4% vs. 8.0%, respectively), with numerical improvements vs. vehicle control reported at earlier time points.

“The Itch response occurred very quickly, and at Day 4, there was a significant improvement in itch in the patient treated with topical ruxolitinib,” Shawn Kwatra, MD, Joseph W. Burnett Endowed Professor and Chair of Dermatology at University of Maryland School of Medicine and Chief of Service Dermatology at the University of Maryland Medical Center in Baltimore, MD, tells TDD. “Fully 44% of patients who received topical ruxolitinib had a significant itch response and a significant improvement in skin lesions.”

Additionally, the TRuE-PN1 study met all key secondary endpoints, including:

• Significantly more patients who applied ruxolitinib cream 1.5% vs. 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%, respectively).
• As a result, significantly more patients who applied ruxolitinib cream 1.5% vs. vehicle control achieved overall treatment success (11.9% vs 2.9%, respectively), defined by patients achieving both WI-NRS4 response and an IGA-CPG-S-TS at Week 12; and,
• Significantly more patients treated with ruxolitinib cream 1.5% vs. vehicle control also achieved WI-NRS4 at Week 4 (29.7% vs. 12.7%, respectively).

He says the more treatment options for PN, the better for patients. “PN is an intensely itchy skin disease, and for many years, there were no approved therapies,” he says. “We are going through the Golden Age for PN now, where we have two approved therapies, but there is certainly room for a topical agent.”  Dupilumab (Dupixent, Sanofi & Regeneron) and nemolizumab (Nemluvio, Galderma) are the only U.S. Food and Drug Administration-approved drugs for PN.

PN has a profound effect on patients’ quality of life. “Itch is an incredibly disabling disease that leads to sleep disturbance., and the appearance of these skin lesions can be socially incredibly disruptive.”

Before this Golden age, PN was treated with off-label therapy that was not very effective.”

Diagnosing PN can be a slam dunk, he says.

“PN is a very straightforward disease to diagnose,” Dr. Kwatra says. “All you need is chronic itch for six weeks or longer, nodules, pustules, excoriation, and scratching; You don’t need a biopsy as that can confuse the clinical picture.”

Topline data from a separate Phase 3 study, TRuE-PN2, showed that while the primary endpoint did not reach statistical significance, the primary and all key secondary endpoints were in favor of ruxolitinib cream 1.5% vs. vehicle. This study did demonstrate a strong positive trend across all key secondary endpoints, particularly for IGA-CPG-S-TS at Week 12 and WI-NRS4 at Day 7.

Data from the TRuE-PN2 study will be submitted for presentation at an upcoming scientific meeting. The findings from the TRuE-PN1 and TRuE-PN2 studies will inform planned discussions with regulatory authorities to determine the next steps.

The overall safety profile of ruxolitinib cream 1.5% in the TRuE-PN clinical trial program is consistent with previous data, and no new safety signals were observed.

More About the TRuE-PN Study Design

The TRuE-PN clinical trial program includes two Phase 3 studies, TRuE-PN1 (NCT05755438) and TRuE-PN2 (NCT05764161), evaluating the safety and efficacy of twice-daily ruxolitinib cream 1.5% in patients with prurigo nodularis (PN). Both studies include a 12-week double-blind, vehicle-controlled treatment period, followed by a 40-week open-label extension and 30-day safety follow-up.

The studies have each enrolled approximately 180 patients (age ≥18 years) diagnosed with PN and meet certain criteria: ≥6 pruriginous lesions on ≥2 different body areas (such as right and left leg) at screening and baseline having a treatment area <20% body surface area (BSA); Investigator’s Global Assessment for Stage of Chronic Prurigo Treatment Success (IGA-CPG-S) score of ≥2 at screening and baseline; and baseline PN-related Worst-Itch Numeric Rating Scale (WI-NRS) score ≥7.

The primary endpoint for both studies is the reduction in the WI-NRS4 response at week 12, defined as achieving a ≥4-point improvement (reduction) in WI-NRS score from baseline. Key secondary endpoints include overall treatment success (both WI-NRS4 response and IGA-CPG-S-TS) at Week 12, IGA-CPG-S-TS at Week 12, and WI-NRS4 response at Day 7 and Week 4. Additional secondary endpoints include WI-NRS4 at each post-baseline visit for up to 52 weeks and changes from the baseline in the WI-NRS score. The studies also track the frequency, duration, and severity of adverse events associated with the use of ruxolitinib cream.

“It’s an original study design,” Dr. Kwatra says. “We spent a lot of time thinking critically about how to design a study for a topical agent in PN.”