Two phase 3 studies met their main endpoint
Once-daily povorcitinib, an oral drug designed to selectively inhibit JAK1, produced significantly greater facial repigmentation than placebo in adults with moderate-to-severe nonsegmental vitiligo in two randomized phase 3 trials.
The results come from STOP-V1 and STOP-V2, parallel double-blind, placebo-controlled studies reported in Nature Medicine. Together, the trials enrolled 916 adults: 467 in STOP-V1 and 449 in STOP-V2. Participants received either 30 mg of povorcitinib once daily or placebo, and the primary results were assessed at 52 weeks.
Vitiligo is a condition in which areas of skin lose pigment. The study focused on nonsegmental vitiligo, the more widespread form of the disease, in people considered candidates for systemic treatment. The investigators said there remains an unmet need for therapies that can promote repigmentation in this population.
Facial repigmentation was more frequent with treatment
The primary endpoint in both trials was F-VASI75: at least a 75% improvement from baseline in the facial Vitiligo Area Scoring Index at week 52. Both studies met that endpoint.
- In STOP-V1, 18.9% of people receiving povorcitinib reached F-VASI75, compared with 6.8% receiving placebo.
- In STOP-V2, 18.9% of people receiving povorcitinib reached F-VASI75, compared with 3.1% receiving placebo.
The difference was statistically significant in each study. In STOP-V1, the reported odds ratio was 3.1, with a 95% confidence interval of 1.6 to 5.9 and a P value of 0.0003. In STOP-V2, the odds ratio was 7.5, with a 95% confidence interval of 3.0 to 18.6 and a P value below 0.0001.
Those figures describe the proportion of participants who achieved the study’s high bar for facial improvement; they do not mean that every participant experienced that level of repigmentation. Still, the consistency of the primary-endpoint result across two separately run studies is central to the report’s conclusion.
Safety findings require context
The researchers described povorcitinib as well tolerated over the 52-week study period. Treatment-emergent adverse events occurred at broadly similar rates in the active-treatment and placebo groups.
In STOP-V1, 68.7% of participants taking povorcitinib reported at least one treatment-emergent adverse event, versus 63.7% in the placebo group. In STOP-V2, the corresponding figures were 66.7% and 62.7%.
The most commonly reported events among participants receiving povorcitinib were nasopharyngitis, acne and upper respiratory tract infection. Nasopharyngitis occurred in 11.2% of treated participants in STOP-V1 and 11.3% in STOP-V2, compared with 9.8% and 11.1% in the respective placebo groups. Acne was reported in 10.7% and 10.8% of treated participants, versus 3.0% and 2.2% with placebo. Upper respiratory tract infection was reported in 6.9% and 14.0% of treated participants, compared with 9.0% and 10.7% in the placebo groups.
Serious treatment-emergent adverse events were generally single events, according to the paper. The authors also reported that adverse events associated with the Janus kinase inhibitor drug class were absent or rare in these trials. These findings describe the results observed in the studies and should not be read as a substitute for an individual clinical risk assessment.
Why the trials matter
Povorcitinib is being studied as a systemic option, meaning it is taken by mouth and acts throughout the body rather than being applied only to affected skin. The reported results suggest that selective JAK1 inhibition can produce clinically meaningful facial repigmentation for a portion of adults with moderate-to-severe nonsegmental vitiligo.
For patients and clinicians, the outcome also illustrates the importance of looking beyond a headline percentage. The trial endpoint was specific to facial disease and required a substantial improvement after a full year of treatment. The paper does not establish that all people with vitiligo will respond similarly, nor does it replace the need to weigh treatment benefits and risks in the context of a patient’s disease and health history.
Nevertheless, STOP-V1 and STOP-V2 provide large, controlled 52-week datasets for a condition with limited systemic repigmentation options. The authors conclude that the results support once-daily povorcitinib as an effective and well-tolerated systemic treatment for adults with moderate-to-severe nonsegmental vitiligo. The trials are registered as NCT06113445 and NCT06113471.
This article is based on reporting by Nature Medicine. Read the original article.
Originally published on nature.com
