Summary
In two 52-week placebo-controlled phase 3 trials, once-daily povorcitinib improved facial repigmentation in adults with moderate-to-severe nonsegmental vitiligo. The primary response threshold was reached by 18.9% of participants taking the drug in each trial.
Two phase 3 trials found that once-daily povorcitinib improved facial repigmentation compared with placebo in adults with moderate-to-severe nonsegmental vitiligo over 52 weeks. The trials enrolled 916 adults in total and both met their primary endpoint. Povorcitinib is an oral, selective JAK1 inhibitor; it is being studied as a systemic treatment for vitiligo.
What the trials measured
STOP-V1 and STOP-V2 were randomized, double-blind, placebo-controlled studies. Participants received either povorcitinib 30 mg once daily or placebo for 52 weeks. The primary measure was F-VASI75: at least a 75% improvement from baseline on the facial Vitiligo Area Scoring Index. The index combines the area of facial skin affected with the degree of depigmentation, so the endpoint is a change in a scored measure, not a claim that 75% of a person’s face regained pigment.
Vitiligo involves the loss of melanocytes, the cells that produce skin pigment. In nonsegmental vitiligo, immune activity involving the JAK–STAT signaling pathway contributes to the recruitment of cytotoxic T cells that damage melanocytes. Povorcitinib selectively inhibits JAK1, a part of this signaling system.
Repigmentation gains and safety
At week 52, 18.9% of participants taking povorcitinib reached F-VASI75 in each trial. The corresponding placebo rates were 6.8% in STOP-V1 and 3.1% in STOP-V2. The odds ratios were 3.1 (95% confidence interval 1.6–5.9) and 7.5 (95% confidence interval 3.0–18.6), respectively. Participants’ own ratings of facial noticeability also favoured povorcitinib: 15.1% and 10.2% reported that facial vitiligo was a lot less noticeable or no longer noticeable, compared with 3.2% and 1.6% on placebo.
Total-body improvement was more modest. At week 52, at least 50% improvement on the total-body VASI was recorded in 18.4% of the povorcitinib group versus 6.5% of placebo recipients in STOP-V1, and 12.9% versus 4.8% in STOP-V2. The more demanding threshold of at least 75% total-body improvement was reached by few participants: the difference was not statistically significant in STOP-V1, while rates in STOP-V2 were 2.3% with povorcitinib and 0% with placebo.
The proportion reporting any treatment-emergent adverse event was similar between groups: 68.7% with povorcitinib and 63.7% with placebo in STOP-V1, and 66.7% and 62.7% in STOP-V2. Acne was more common with povorcitinib, occurring in about 11% of treated participants in each trial, compared with 3.0% and 2.2% on placebo. One participant taking povorcitinib in STOP-V2 experienced pulmonary embolism and other thrombotic events that investigators considered related to treatment. The trials excluded people with a history of venous or arterial thrombosis and some other significant health conditions, a factor to keep in mind when interpreting safety findings.
The results provide controlled evidence of facial repigmentation with povorcitinib over one year, while the low total-body response rates at the 75% threshold show that outcomes varied by measure. The studies had no active-treatment comparator, assessed povorcitinib as monotherapy, and enrolled a population that was about 80–85% white. Their 52-week open-label extension is ongoing.