Incyte’s povorcitinib met the primary endpoint in two Phase 3 vitiligo trials, demonstrating significant facial repigmentation at Week 52.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Incyte’s oral JAK1 inhibitor povorcitinib met the primary endpoint in two Phase 3 trials evaluating adults with moderate-to-severe nonsegmental vitiligo (NSV). The STOP-V1 and STOP-V2 studies demonstrated statistically significant improvements in facial repigmentation at Week 52, with 18.9% of treated patients achieving at least 75% improvement from baseline in both trials. However, substantial facial repigmentation remained limited to fewer than one in five patients.
Vitiligo is a chronic autoimmune condition characterized by the destruction of melanocytes, resulting in depigmented skin patches. NSV, the most common form of the disease, can affect extensive body areas and carry substantial psychosocial and quality-of-life burdens. Although topical ruxolitinib is an approved treatment in several regions, systemic treatment options for patients with moderate-to-severe disease remain an area of unmet need.
Published in Nature Medicine on November 2, 2026, the findings provide replicated Phase 3 evidence for systemic JAK1 inhibition in NSV, while highlighting the remaining challenges in achieving substantial facial and total-body repigmentation.
Two Phase 3 trials evaluated oral JAK1 inhibition
STOP-V1 (NCT06113445) and STOP-V2 (NCT06113471) were randomized, double-blind, placebo-controlled studies enrolling 467 and 449 adults, respectively, with moderate-to-severe NSV. Participants had vitiligo affecting at least 0.5% of facial body surface area and 5% of total body surface area and were candidates for systemic treatment.
Patients received povorcitinib 30 mg or placebo once daily for 52 weeks, followed by a planned 52-week open-label extension in which all participants receive povorcitinib. The extension remains ongoing.
The primary endpoint was the proportion of patients achieving at least 75% improvement from baseline in the Facial Vitiligo Area Scoring Index (F-VASI75) at Week 52.
Both trials met the primary endpoint
At Week 52, 18.9% of povorcitinib-treated patients achieved F-VASI75 in both trials, compared with 6.8% in STOP-V1 and 3.1% in STOP-V2 receiving placebo.
Week 52 outcome | STOP-V1: Povorcitinib vs placebo | STOP-V2: Povorcitinib vs placebo |
F-VASI75 | 18.9% vs 6.8% | 18.9% vs 3.1% |
Facial VNS score 4 or 5 | 15.1% vs 3.2% | 10.2% vs 1.6% |
T-VASI50 | 18.4% vs 6.5% | 12.9% vs 4.8% |
T-VASI75 | 2.6% vs 1.3% | 2.3% vs 0% |
Change in T-VASI | −24.1% vs −5.7% | −21.1% vs −4.4% |
F-VASI: Facial Vitiligo Area Scoring Index; T-VASI: Total Vitiligo Area Scoring Index; VNS: Vitiligo Noticeability Scale.
The primary endpoint was statistically significant in both studies. Facial noticeability also improved, with more patients reporting that their vitiligo was substantially less noticeable or no longer noticeable.
However, the absolute response rate highlights an important limitation: approximately 81% of treated patients did not achieve F-VASI75 after one year. This does not mean they experienced no improvement, but it underscores the difference between statistical efficacy and substantial clinical repigmentation.
Total-body response and disease stabilization
Povorcitinib also improved total-body repigmentation. T-VASI50 responses were significantly higher than placebo in both trials. Mean total-body VASI scores declined by 24.1% in STOP-V1 and 21.1% in STOP-V2, compared with 5.7% and 4.4% with placebo, respectively.
However, more substantial total-body improvement remained uncommon. T-VASI75 was not statistically significant in STOP-V1, while STOP-V2 showed a significant difference despite only 2.3% of treated patients achieving this threshold.
Exploratory post hoc analyses also suggested potential disease stabilization. The proportion of patients without an increase in total-body VASI was 94.3% versus 71.8% in STOP-V1 and 87.6% versus 69.2% in STOP-V2, favouring povorcitinib. These findings suggest a possible benefit beyond repigmentation, although they require confirmation.
Facial repigmentation continued to improve through Week 52 without an observed plateau. Nevertheless, longer follow-up is needed to establish the extent and durability of additional responses.
Safety profile and notable events
Overall treatment-emergent adverse event (TEAE) rates were broadly similar between treatment groups. TEAEs occurred in 68.7% versus 63.7% of participants in STOP-V1 and 66.7% versus 62.7% in STOP-V2, for povorcitinib and placebo, respectively.
Reported events included nasopharyngitis, acne, upper respiratory tract infections and increased blood creatine phosphokinase (CPK). CPK elevations led to treatment discontinuation in five patients, with several cases associated with intense physical activity or work-related exertion. Discontinuations due to TEAEs were also slightly higher with povorcitinib.
Four patients receiving povorcitinib developed basal cell carcinoma, one in STOP-V1 and three in STOP-V2, compared with none receiving placebo. One case was considered treatment-related and resulted in treatment discontinuation.
In STOP-V2, one patient experienced pulmonary embolism, deep vein thrombosis and thrombosis involving a varicose vein. Investigators considered these events treatment-related. The patient had additional potential risk factors, including varicose veins, rheumatoid arthritis, hypertension, smoking and a recent Mycoplasma pneumoniae infection.
No major adverse cardiovascular events, tuberculosis cases or deaths were reported during the controlled study period. However, the malignancy and thromboembolic observations warrant continued safety monitoring.
Clinical interpretation and limitations
The STOP-V trials provide replicated Phase 3 evidence that oral JAK1 inhibition can improve facial repigmentation in adults with moderate-to-severe NSV. The consistent F-VASI75 response across both studies, alongside improvements in facial noticeability and T-VASI50, supports further evaluation of povorcitinib as a systemic treatment option.
However, the relatively low absolute facial response rate and limited achievement of T-VASI75 highlight the remaining challenge of restoring pigmentation across extensive affected areas. Exploratory disease-stabilization findings offer an additional potential benefit but should not be interpreted as definitive evidence of preventing disease progression.
The absence of an active comparator, predominantly White study populations, monotherapy design and 52-week placebo-controlled follow-up limit conclusions about comparative effectiveness, broader generalizability and long-term safety. The ongoing open-label extension may provide further evidence on treatment durability and safety.
For Incyte, the results represent an important late-stage clinical milestone. However, the clinical value of povorcitinib will ultimately depend on the durability of repigmentation, its long-term risk profile and the extent of benefit across different patient populations.
Reference
Ezzedine, K., Lui, H., Eleftheriadou, V. et al. Povorcitinib for nonsegmental vitiligo: two randomized, controlled, phase 3 STOP-V trials. Nat Med (2026). https://doi.org/10.1038/s41591-026-04739-2
A Study to Evaluate Efficacy and Safety of Povorcitinib in Participants with Nonsegmental Vitiligo (STOP-V1), ClinicalTrials.gov ID NCT06113445
A Study to Evaluate Efficacy and Safety of Povorcitinib in Participants with Nonsegmental Vitiligo (STOP-V2), ClinicalTrials.gov ID NCT06113471
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.