For Opzelura, Positive Results from One Trial, Less So From Another | AAD 2025

When the FDA approved Dupixent (dupilumab) as a treatment for prurigo nodularis in 2022, it was a first. Other drugs had been used to treat the skin condition, but Dupixent, which is injected, was the first with an FDA-approved indication.

Now the race is on for other treatments for prurigo nodularis. The FDA approved Nemluvio (nemolizumab), another subcutaneous injection, as a treatment in August 2024. And today at the 2025 meeting of the American Academy of Dermatology, positive results were reported for Opzelura (1.5% ruxolitinib), a topical treatment that the FDA has previously approved for atopic dermatitis and vitiligo.

Shawn Kwatra, M.D., a professor at the University of Maryland School of Medicine and chair of its dermatology department, said the Opzelura phase 3 results that he was presenting were the first for a topical treatment of prurigo nodularis. The main symptom of the condition is hard, itchy nodules on the skin. The itching can be severe, and patients end up in an itch-scratch cycle that harms the skin further. In response to a question after his presentation at the late-breaking research session, Kwatra said that going into this study one of his concerns was whether a cream would be effective for a skin condition that involves skin thickening and fibrosis.

When it announced the approval of Dupixent, the FDA, quoting the National Organization for Rare Diseases, said 87,000 adults per year are affected by prurigo nodularis. In a press release today about the findings that Kwatra presented, Incyte, the maker of Opzelura, said that there are approximately 200,000 people in the U.S. living with disease.

The data that Kwatra presented are from the TRuE-PN1 study, sponsored by Incyte, in which approximately 200 patients with prurigo nodularis were randomly assigned to either treatment with Opzelura or a placebo cream. Primary endpoint was a four-point or better improvement in the Worst-Itch Numeric Rating Scale (WI-NRS), a way of measuring itch that resembles the way in which pain is measured. Patients are asked to rate the intensity of their itchiness in the past 24 hours on an 11-point scale, with 0 being no itch and 10 being the worst itch imaginable. After 12 weeks, 44.6% of the 101 patients in the Opzelura group met that end point compared with 20.6% of the 102 patients in the control group. Kwatra also showed data on secondary end points that supported the effectiveness of Opzelura and that the difference between the treatment and the placebo occurred early on in the trial. He described the safety data as having no surprises. More people in the Opzelura group experience nasopharyngitis.

Kwatra also presented preliminary data from a similarly designed companion trial, TRuE-PN2, although in less detail than the data he presented from TRuE-PN1. The results from TRuE-PN2 showed much less of a difference between the Opzelura group and the placebo group on the primary end point of four-point or better improvement in the WI-NRS measurement. The TRuE-PN2 data that Kwatra shared showed that after 12 weeks, a similar proportion — 40%— of the 93 patients randomly assigned to the Opzelura group had met the four-point drop in the WI-NRS end point as in the Opzelura group in TRuE-PN1. But 36.2% of those randomly assigned to the placebo group also met the end point, which works out to a 3.8 percentage point difference between the treatment and the placebo group compared with the 20 percentage point difference seen in TRuE-PN1. The differences in the outcomes on secondary end points between the treatment and placebo groups were also narrower in TRuE-PN2 than in TRuE-PN1.

The news release from Incyte says that the topline data from TRuE-PN2 “demonstrated a strong positive trend across all key secondary end points” while acknowledging that statistical significance was not met in the primary end point.

The news release says that the “findings from the TRuE-PN1 and TRuE-PN2 studies will inform planned discussions with regulatory authorities to determine next steps.”