The topical JAK inhibitor, already approved for vitiligo and atopic dermatitis, showed significant itch and skin improvements in prurigo nodularis patients.

Phase 3 trial findings highlight the potential of ruxolitinib (Opzelura) cream 1.5% as a topical treatment for prurigo nodularis (PN), showing significant itch relief and skin improvement in patients.

Incyte’s pivotal phase 3 TRuE-PN clinical trial program—TRuE-PN1 and TRuE-PN2 studies—evaluated the safety and efficacy of the twice-daily cream, a JAK1/2 inhibitor, in adult patients with PN.

The TRuE-PN1 study met its primary endpoint, demonstrating that significantly more PN patients who applied ruxolitinib cream 1.5% versus 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%; P=0.0003). Significant itch improvements were observed with ruxolitinib cream 1.5% versus vehicle control at day 7 (22.4% vs 8.0%; P=0.0064), with numerical improvements versus vehicle control reported at earlier timepoints. 

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

  • Significantly more patients who applied ruxolitinib cream 1.5% 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).
  • As a result, significantly more patients who applied ruxolitinib cream 1.5% versus vehicle control achieved overall treatment success (11.9% vs 2.9%; P=0.0164), 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% versus vehicle control also achieved WI-NRS4 at Week 4 (29.7% vs 12.7%, P=0.0034).

“PN is a challenging condition characterized by intensely itchy nodules that significantly impact patients’ quality of life,” says Jim Lee, MD, PhD, group vice president of inflammation and autoimmunity at Incyte, in a release “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.”

Positive Trend Across Secondary Endpoints

Additionally, topline data from the phase 3 TRuE-PN2 clinical trial demonstrated a strong positive trend 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). While the primary endpoint was in favor of ruxolitinib cream 1.5% versus vehicle, it did not reach statistical significance due to high placebo response. Data from the TRuE-PN2 study will be submitted for presentation at an upcoming scientific meeting.

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.

“This program includes the first clinical trials evaluating a topical JAK inhibitor for the treatment of patients with PN, a condition associated with the formation of cutaneous nodules across the body that cause persistent itch and discomfort,” says 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 a release. “In TRuE-PN1, ruxolitinib cream 1.5% demonstrated its ability to significantly improve itch and PN lesions, and I believe it has the potential to be a much-needed novel approach for PN patients.”

The findings from the TRuE-PN1 and TRuE-PN2 studies will inform planned discussions with regulatory authorities to determine next steps.

Ruxolitinib cream 1.5% (Opzelura) was approved by the US Food and Drug Administration 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 whose disease is not adequately controlled with topical prescription therapies in 2022 and 2021, respectively.

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