Ritlecitinib 100 mg once daily drove a 21.86% Facial Vitiligo Area Scoring Index 75% improvement (F-VASI75) rate at week 52 in nonsegmental vitiligo, against 2.40% on placebo in the phase 3 TRANQUILLO 2 trial. The 50 mg dose in the sister TRANQUILLO study hit 12.47% F-VASI75 versus 2.48% on placebo.

Pfizer reported the data October 2, 2026, in a late-breaking oral presentation at the 35th European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna. The company called TRANQUILLO and TRANQUILLO 2 the largest phase 3 program to date evaluating an oral systemic therapy for nonsegmental vitiligo (NSV).

How were the trials designed?

TRANQUILLO 2 (NCT06072183) randomized 1,567 adults to ritlecitinib 100 mg once daily, with an exploratory, descriptive 50 mg arm. TRANQUILLO (NCT05583526) enrolled 607 patients aged 12 and older on 50 mg once daily. Together, the two trials covered 2,174 patients at 271 sites worldwide.

In the US, the co-primary end points were F-VASI75 and at least 50% improvement in the Total Vitiligo Area Scoring Index (T-VASI50) at week 52. Outside the US, F-VASI75 stood as the primary end point and T-VASI50 as a key secondary.

T-VASI50 responses reached 13.02% in TRANQUILLO 2 and 8.98% in TRANQUILLO, compared with 2.40% and 1.98% on placebo. Pfizer reported statistically significant separation from placebo on both co-primary end points in each trial.

How early did the drug separate from placebo?

Across both studies, F-VASI and T-VASI improvements over placebo reached significance as early as week 24 and grew through weeks 36 and 52. More patients on ritlecitinib cleared the F-VASI75 and T-VASI50 thresholds at every interim analysis.

On patient-reported measures, more participants rated their facial vitiligo and overall disease as less severe at week 52. The Patient Global Impression of Change for the face (PGIC-F) and overall vitiligo (PGIC-V), plus the Vitiligo Noticeability Scale (VNS), all favored active treatment.

The exploratory 50 mg arm in TRANQUILLO 2 also produced clinically meaningful gains over placebo on F-VASI75 and T-VASI50 at week 52, though those comparisons were not controlled for type I error.

What is the safety profile in vitiligo?

Pfizer characterized the NSV safety profile as consistent with the established label in severe alopecia areata. The company reported no new safety signals. Treatment-emergent adverse events (TEAEs) occurred in 67.7% of patients on 100 mg and 62.0% on placebo in TRANQUILLO 2, and in 81.0% versus 77.1% in TRANQUILLO.

In TRANQUILLO 2, the most common TEAEs were upper respiratory tract infection (8.9% vs 3.4% with placebo), nasopharyngitis (7.9% vs 7.3%), and headache (4.0% vs 5.4%). TRANQUILLO listed upper respiratory tract infection (14.0% vs 10.9%), increased blood creatine phosphokinase (11.0% vs 8.0%), and nasopharyngitis (10.5% vs 9.5%).

Decreased lymphocyte count occurred in 6.3% on ritlecitinib versus 1.5% on placebo. Patients on the 100 mg and placebo arms in TRANQUILLO 2 recorded treatment-emergent serious AEs at 3.4% for both groups, and at 2.0% versus 2.5% in TRANQUILLO.

Where does ritlecitinib fit clinically?

The drug, marketed as Litfulo, already holds FDA approval for severe alopecia areata in adults and adolescents aged 12 and older. Pfizer positioned the molecule as a dual inhibitor of Janus kinase 3 (JAK3) and the TEC family kinases — signals immune cells use to attack pigment-producing cells in the skin.

Iltefat Hamzavi, MD, senior staff physician in the department of dermatology at Henry Ford Health and Hamzavi Dermatology Specialists, said in the Pfizer release: "The results solidify the potential of LITFULO to support a new treatment paradigm rooted in systemic treatment that can address underlying disease drivers for people living with nonsegmental vitiligo."

Pfizer stated it intends to file the dataset with the FDA and the European Medicines Agency. The company is also running TRANQUILLO LTE, a long-term extension trial, to follow patients beyond the 52-week primary analysis.

FDA and EMA submissions are now in motion, and the long-term extension will determine whether efficacy and safety hold beyond week 52 in nonsegmental vitiligo.