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Jump to Key Points Ritlecitinib, an oral JAK inhibitor approved for the treatment of alopecia, met all of the efficacy endpoints at week 24 in a global pivotal phase 3 trial program for the treatment of vitiligo.
In data combined from two trials, the benefit on the primary endpoints at week 24 “increased through week 52 without plateau,” reported Iltefat H. Hamzavi, MD, a dermatologist and researcher associated with Henry Ford Hospital in Dearborn, Michigan.
Improvements in objective clinical measures of disease were accompanied by highly positive responses on patient-reported outcomes, according to Hamzavi, who delivered the data in a latebreaker presentation at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna.
1600-Plus Patients Randomly Assigned in Two Trials
In the larger of the two 52-week trials, called TRANQUILLO Part 1a, 1036 patients with moderate-to-severe vitiligo were randomly assigned to 50 mg of ritlecitinib, 100 mg of ritlecitinib, or placebo taken orally once daily. The randomization, involving 229 sites in 15 countries, was 1:2:1 for the three groups, respectively.
- Oral ritlecitinib met all week-24 efficacy endpoints in 2 phase 3 vitiligo trials.
- 1600+ pts randomized; doses 50 mg and 100 mg QD showed similar efficacy.
- F-VASI75: 21.9%/19.9% vs placebo <2.5%; T-VASI50: 13.0%/12.6%; all P<.0001.
- Responses continued rising through 52 weeks; no plateau, with patient-reported benefit.
- Safety generally similar to placebo; ↑ URTI, CPK, lymphopenia; no major CV/malignancy signal.
In the other trial, 600 patients were randomly assigned in a 2:1 ratio to 50 mg ritlecitinib or placebo at 115 sites in 18 countries.
The co-primary endpoints in both studies were at least a 75% improvement from baseline in the Facial Vitiligo Area Scoring Index (F-VASI75) and at least a 50% improvement in Total Vitiligo Area Scoring Index (T-VASI50).
The two doses of ritlecitinib performed similarly in TRANQUILLO Part 1a. With nominal responses to placebo in both studies (less than 2.5%), the proportion of patients achieving F-VASI75 scores (21.9% and 19.9% for the higher and lower doses, respectively) was highly statistically significant (P < .0001) relative to baseline or placebo. The same was true of the T-VASI50 responses (13.0% and 12.6%, respectively; P < .0001) for ritlecitinib relative to baseline or placebo.
In TRANQUILLO, the responses in the single active treatment arm of 50 mg ritlecitinib were lower for both F-VASI75 (12.5%) and T-VASI50 (9.0%) than they were in TRANQUILLO Part 1a, but the differences from baseline for each remained highly significant (P < .0001).
Response Rates Continued to Climb Over 52 Weeks
When compared over the course of the two studies, the advantage of either dose of ritlecitinib relative to placebo was numerically greater by week 12 and then climbed steadily for the remainder of the 52-week trial. The response curves for ritlecitinib were still climbing at 52 weeks.
These changes were clinically meaningful to patients as measured by the Patient Global Impression of Change in vitiligo overall (PGIC-V), the PGI for the face specifically (PGIC-F), the PGI of vitiligo severity overall (PGIS-V), the PGI of vitiligo severity for the face specifically (PGIS-F), and the patient-assessed Vitiligo Noticeability Scale (VNS).
For PGIC-V in the TRANQUILLO Part 1a study, response defined as at least moderately better was met by 36.3% of those on the 100-mg dose of ritlecitinib, 25.7% on the 50-mg dose, and 2.9% on placebo. The rates for PGIC-F were 37.3%, 31.1%, and 6.7%, respectively. TRANQUILLO patient-reported outcomes were similar.
The proportions with at least a moderate improvement on PGIS-V in TRANQUILLO Part 1a were 32.3% of those randomly assigned to the 100-mg dose, 27.8% of those randomly assigned to the 50-mg dose, and 17.3% of those randomly assigned to placebo. Response rates for PGIS-F were 42.9%, 33.5%, and 18.3%, respectively.
A response on VNS, defined as a score of 4 (meaning a lot less noticeable) or 5 (meaning no longer noticeable), was achieved in 19.9%, 14.6%, and 1.0% of the 100-mg, 50-mg, and placebo groups in TRANQUILLO Part 1a, respectively, and in 12.0% and 4.5% of the 50-mg and placebo groups in TRANQUILLO, respectively.
Unlike the placebo groups, which lost response over time, a significantly greater proportion of patients receiving ritlecitinib at any dose achieved and maintained stabilization in the study overall and between weeks 24 and 52 specifically, Hamzavi reported.
The rates of adverse events were generally similar for the active treatment arms relative to placebo in both studies. In the TRANQUILLO Part 1a study, the exception was a greater rate of upper respiratory tract infections, which were observed in 8.9% of those randomly assigned to 100-mg ritlecitinib, 6.8% of those randomly assigned to 50-mg ritlecitinib, and 3.4% of those randomly assigned to placebo.
No Major Safety Concerns Identified
In TRANQUILLO, upper respiratory tract infection rates were also higher with ritlecitinib than placebo (14.0% vs 10.9%). Rates of elevated blood creatine phosphokinase (11.0% vs 8.0%) and decreased lymphocyte counts (6.3% vs 1.5%) were also higher with ritlecitinib than placebo. None were serious. There was no signal for increased rates of malignancy, viral infections, opportunistic infections, or thrombotic or cardiovascular events, according to Hamzavi.
“The safety profile was consistent with prior ritlecitinib studies, with no new safety signals identified,” he said.
The only JAK inhibitor currently approved for vitiligo is ruxolitinib, a topical agent with selectivity for JAK1 and JAK2 subtypes. Ritlecitinib has greater relative specificity for JAK3 and also inhibits TEC kinases. If approved, it would be not only the first oral JAK inhibitor but also the first oral therapy of any kind available for vitiligo, according to Hamzavi.
Relative to placebo, the 20% F-VASI75 response reported in the TRANQUILLO trials was highly statistically significant. John E. Harris, MD, PhD, chair of dermatology at Harvard Medical School’s Mass General Brigham, Boston, was asked whether this number is clinically meaningful, and he said it was, given how slowly vitiligo has resolved with other treatments.
“The rate suggests that 1 in 5 patients achieved an acceptable outcome quickly, while the other 80% will take more time,” Harris told Medscape Medical News. Harris, the senior author of a review article on new treatment options in vitiligo, published last year, pointed out that patients treated with the approved topical JAK inhibitor “can continue to improve for 3 years on treatment.”
In other words, the data are encouraging in the sense that follow-up thus far “is early in the treatment journey for a vitiligo patient,” Harris said. Given the limitation of the JAK topical, which he said has been most effective for those with 10% or less body surface area involvement, Harris is hopeful that the oral therapy will offer an efficacy advantage, particularly for those with an actively spreading disease.
The TRANQUILLO studies were sponsored by Pfizer. Hamzavi reported financial relationships with this company and with AbbVie, Ahammune, Almirall, Boehringer Ingelheim, Galderma, Incyte, Janssen, L’Oréal/La Roche-Posay, Merck, Novartis, Takeda, Teva, and Vimela. Harris reported financial relationships with AbbVie, Alys, Barinthus, Cour, Incyte, Matchpoint, Neximmune, and Vividion.
Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology and oncology, for several decades.
