Povorcitinib passes efficacy, safety tests in phase II trial for extensive vitiligo

Treatment with the Janus kinase (JAK) 1 inhibitor povorcitinib results in significant repigmentation of the body and face in adult patients with extensive nonsegmental vitiligo (NSV), with an acceptable safety profile, through 52 weeks, reports a phase II study.

“All doses of povorcitinib were generally well tolerated, and no treatment-related serious adverse events (AEs) were reported,” according to the investigators.

Some 171 adult patients with NSV were randomly assigned 1:1:1:1 to receive once-daily povorcitinib 15, 45, or 75 mg or placebo for 24 weeks. Subsequently, participants received povorcitinib 45 mg (initially randomized to 45 mg) or 75 mg (initially randomized to placebo, 15, or 75 mg) until week 52, followed by 24-week follow-up after treatment.

The participants had a mean total body surface area (BSA) of 28.2 percent and total Vitiligo Area Scoring Index (VASI) of 25.5. Of these, 82.5 percent completed the 24-week treatment. [J Am Acad Dermatol 2025;93:946-955]

Treatment with povorcitinib significantly improved total VASI at week 24 from baseline (15 mg: 19.1 percent; 45 mg: 17.8 percent; 75 mg: 15.7 percent) relative to placebo (‒2.3 percent; least squares mean povorcitinib vs placebo, p<0.01). These improvements persisted through week 52.

“Among patients randomized to placebo, those who crossed over to povorcitinib after week 24 also showed improvement at week 52,” the investigators said.

“Additionally, improvements in total body and facial repigmentation were maintained in a subset of patients for 24 weeks (week 52 to 76) after stopping povorcitinib treatment, although sample sizes during post-treatment follow-up were small, and findings need to be confirmed in larger populations,” they added.

Safety profile

In terms of safety, the incidence of grade ≥3 treatment-emergent AEs did not significantly differ across treatment groups, and no new safety signals were observed after 24 weeks of treatment.

One common AE from taking JAK inhibitors is acne, which occurred in 7.1 percent of patients during placebo control and in 13.8 percent of participants during treatment extension. This AE, however, did not lead to any interruption of cessation in treatment. [J Pers Med 2021;11:279]

Three cases of herpes zoster (grade 1 or 2) also occurred during treatment extension, but none of these were deemed serious.

“These data support further evaluation of the efficacy and safety of povorcitinib in the ongoing global phase III registrational studies of patients with extensive NSV,” the investigators said.

The study was limited by patients lost to follow-up due to the COVID-19 pandemic. In addition, many of the participants were older (median age 50 years), White, and had vitiligo for >10 years.

“Although randomization was stratified by total BSA thresholds (8 percent to 20 percent and >20 percent), there were some imbalances across treatment groups for patients,” the investigators said. “Overall, sample sizes in each treatment group (n=∼40 per group) and during post-treatment follow-up (n≤10 per group) were small, and findings need to be confirmed in larger patient populations.”