Ritlecitinib Improves Repigmentation in Nonsegmental Vitiligo

Pfizer recently announced results from 2 phase 3 trials of ritlecitinib (Litfulo), a once-daily oral therapy for nonsegmental vitiligo (NSV), showing significant improvements in facial and total body repigmentation compared with placebo at week 52. The TRANQUILLO and TRANQUILLO 2 data were presented in a late-breaking oral presentation at the 35th European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria.¹˒² According to Pfizer, the company intends to submit the data to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).¹

Ritlecitinib is currently approved by the FDA for severe alopecia areata in adults and adolescents 12 years and older. Pfizer describes the TRANQUILLO program as the largest phase 3 effort to date evaluating an oral systemic therapy for NSV.¹

TRANQUILLO 2 (NCT06072183) evaluated ritlecitinib 100 mg once daily in 1567 adults and included an exploratory, descriptive assessment of the 50 mg dose. TRANQUILLO (NCT05583526) evaluated 50 mg once daily in 607 patients 12 years and older. Together, the trials enrolled 2174 patients with NSV at 271 sites worldwide.¹

In the US, the co-primary end points were the proportions of patients achieving at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) and at least 50% improvement in the Total Vitiligo Area Scoring Index (T-VASI50) at week 52. Outside the US, F-VASI75 was the primary end point and T-VASI50 was a key secondary end point.¹

F-VASI75 was achieved by 21.86% of patients in TRANQUILLO 2 (100 mg) and 12.47% in TRANQUILLO (50 mg), compared with 2.40% and 2.48% with placebo, respectively. T-VASI50 was achieved by 13.02% and 8.98% of patients taking ritlecitinib, compared with 2.40% and 1.98% with placebo. Pfizer reported significant improvement over placebo for both co-primary end points in each trial.¹

Ritlecitinib Secondary End Points and Safety Profile in Vitiligo

Across both trials, improvements from baseline in F-VASI and T-VASI were significant compared with placebo as early as week 24 and increased through weeks 36 and 52. More patients taking ritlecitinib also achieved F-VASI75 and T-VASI50 at weeks 24 and 36 than those taking placebo. Patient-reported facial and overall disease severity were significantly reduced at week 52.¹

Other selected end points were not controlled for type I error. Patients reported benefit over placebo on the Patient Global Impression of Change for the face (PGIC-F) and for overall vitiligo (PGIC-V). More patients rated their vitiligo as "a lot less" or "no longer" noticeable on the Vitiligo Noticeability Scale (VNS) through week 52, and disease stabilization was greater with both doses from week 24 onward.¹

In the exploratory 50 mg assessment in TRANQUILLO 2, clinically meaningful improvement over placebo was observed for both F-VASI75 and T-VASI50 at week 52.¹

According to Pfizer, the safety profile in NSV was consistent with the established profile in alopecia areata, and no new safety signals were observed. Treatment-emergent adverse events (TEAEs) occurred in 67.7% of patients taking 100 mg and 62.0% taking placebo in TRANQUILLO 2, and in 81.0% taking 50 mg and 77.1% taking placebo in TRANQUILLO.¹

The most common TEAEs in TRANQUILLO 2 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%). In TRANQUILLO, they were 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% vs 1.5%. Treatment-emergent serious AEs occurred in 3.4% for both ritlecitinib 100 mg and placebo in TRANQUILLO 2, and in 2.0% vs 2.5% in TRANQUILLO.¹

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."¹

The TRANQUILLO program also includes a long-term extension trial, TRANQUILLO LTE. Pfizer states the results may position ritlecitinib as a new oral systemic option for adults with NSV, pending regulatory review.¹

References

1. Pfizer's LITFULO significantly improved facial and total body repigmentation in patients with nonsegmental vitiligo. News release. Pfizer Inc. October 2, 2026. Accessed October 2, 2026. https://www.pfizer.com/newsroom/press-releases?field_press_release_type_target_id[22611]=22611
2. Hamzavi I, et al. Efficacy and safety of ritlecitinib in patients with nonsegmental vitiligo (NSV): results from the Tranquillo 2 Part Ia and Tranquillo Phase 3 randomized, double-blind, placebo-controlled, multicenter clinical trials. Presented at: 35th European Academy of Dermatology and Venereology Annual Congress; September 30-October 4, 2026; Vienna, Austria.