Pfizer Reports Positive Phase 3 Results for LITFULO in Nonsegmental Vitiligo
Pfizer Inc. (NYSE: PFE) has announced detailed results from two Phase 3 clinical trials evaluating LITFULO® (ritlecitinib) as a once-daily oral treatment for people living with nonsegmental vitiligo (NSV). The TRANQUILLO 2 and TRANQUILLO studies evaluated the efficacy and safety of LITFULO across patients with varying degrees of disease involvement, with findings demonstrating statistically significant improvements in facial and total-body repigmentation compared with placebo.
The results were presented in a late-breaking oral session at the 35th European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria. According to Pfizer, the two trials represent the largest Phase 3 development program to date evaluating an oral systemic therapy for NSV.
The company said it plans to submit the findings to regulatory authorities worldwide, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), for review.
The data showed that patients receiving LITFULO experienced improvements in measures of facial and overall repigmentation, with responses becoming more pronounced over time. Patient-reported assessments also indicated reductions in perceived facial and overall disease severity, improvements in how noticeable vitiligo appeared to patients, and greater disease stabilization compared with placebo.
LITFULO Demonstrates Improvements in Facial and Total-Body Repigmentation
Nonsegmental vitiligo is a chronic autoimmune condition in which the immune system targets melanocytes, the cells responsible for producing skin pigment. The resulting loss of pigmentation can occur across multiple areas of the body and may affect highly visible regions, including the face, hands and other exposed areas.
Because vitiligo can progress unpredictably, treatment goals include restoring pigmentation, reducing disease activity and helping maintain repigmentation over time. The Phase 3 TRANQUILLO program was designed to evaluate whether an oral systemic approach with ritlecitinib could provide clinically meaningful improvements across these dimensions.
In TRANQUILLO 2, which evaluated LITFULO 100 mg once daily, 21.86% of patients achieved at least a 75% improvement in Facial Vitiligo Area Scoring Index (F-VASI75) at the specified primary assessment point, compared with 2.40% of patients receiving placebo.
In the TRANQUILLO study, which evaluated LITFULO 50 mg once daily, 12.47% of patients achieved F-VASI75 compared with 2.48% receiving placebo.
The studies also evaluated total-body repigmentation using the Total Vitiligo Area Scoring Index. In TRANQUILLO 2, 13.02% of patients receiving LITFULO achieved at least a 50% improvement in T-VASI (T-VASI50), compared with 2.40% of patients receiving placebo. In TRANQUILLO, the corresponding rates were 8.98% with LITFULO 50 mg and 1.98% with placebo.
These findings formed the basis of the co-primary efficacy assessment in the U.S. trials.
Improvements Increased Over Time
Beyond the primary endpoints, the Phase 3 results indicated that improvements in both facial and total-body repigmentation emerged relatively early and increased with longer treatment.
Across the two studies, statistically significant improvements from baseline in F-VASI and T-VASI were observed as early as Week 24. The separation between LITFULO and placebo continued through Week 36 and Week 52.
The company also reported that more patients receiving LITFULO reached clinically meaningful thresholds of repigmentation at earlier time points. This included the F-VASI75 and T-VASI50 measures at Weeks 24 and 36.
The progressive nature of the response is relevant because repigmentation in vitiligo can require sustained treatment. The Phase 3 findings therefore provide data not only on whether patients responded but also on the durability and trajectory of improvement during the 52-week treatment period.
At Week 52, LITFULO was also associated with statistically significant reductions in patient-reported facial and overall vitiligo severity compared with placebo.
Michael Vincent, M.D., Ph.D., chief inflammation and immunology officer at Pfizer, said the results demonstrate increasing improvements over time in both facial and total-body repigmentation.
“LITFULO has dual selectivity for JAK3 and the TEC family kinases,” Vincent said, adding that these pathways are involved in immune signaling associated with attacks on pigment-producing cells.
He said the results from TRANQUILLO 2 and TRANQUILLO demonstrate the potential of LITFULO as a systemic treatment approach for people living with NSV and that Pfizer plans to engage with regulators regarding the findings.
Patient-Reported Outcomes Add to Clinical Findings
The TRANQUILLO program also incorporated patient-reported measures to assess how changes in pigmentation and disease activity translated into patients’ perceptions of their condition.
At Week 52, LITFULO significantly reduced patient-reported facial and overall vitiligo severity compared with placebo.
Additional exploratory and selected endpoints also showed differences between treatment and placebo groups. Patients receiving ritlecitinib reported meaningful improvements in their global impression of change for both facial vitiligo and overall vitiligo.
The Vitiligo Noticeability Scale (VNS) also improved through Week 52. More patients receiving LITFULO reported that their vitiligo was “a lot less” noticeable or “no longer” noticeable compared with patients receiving placebo.
Disease stabilization was another area in which LITFULO demonstrated a difference from placebo. According to Pfizer, patients receiving ritlecitinib at both evaluated dose levels experienced greater disease stabilization beginning at Week 24, with stabilization maintained through Week 52.
In an assessment of the 50 mg dose in TRANQUILLO 2, the company also reported clinically meaningful improvements compared with placebo in both F-VASI75 and T-VASI50 at Week 52.
Together, these patient-reported and disease-stabilization findings complement the objective repigmentation measures, providing additional information about the potential impact of treatment from the patient perspective.
Safety Profile Remained Consistent With Established Experience
Pfizer reported that the safety profile of LITFULO in patients with NSV was consistent with the medicine’s established safety profile in alopecia areata. The company said no new safety signals were identified in the Phase 3 vitiligo studies.
Treatment-emergent adverse events (TEAEs) occurred at generally similar rates between active-treatment and placebo groups.
In TRANQUILLO 2, TEAEs were reported in 67.7% of patients receiving LITFULO 100 mg compared with 62.0% of patients receiving placebo.
The most frequently reported TEAEs in the study included upper respiratory tract infection, which occurred in 8.9% of patients receiving LITFULO compared with 3.4% with placebo; nasopharyngitis, reported in 7.9% and 7.3%, respectively; and headache, reported in 4.0% and 5.4%.
In TRANQUILLO, TEAEs were reported in 81.0% of patients receiving LITFULO 50 mg and 77.1% of those receiving placebo.
The most common adverse events in TRANQUILLO included upper respiratory tract infection at 14.0% versus 10.9%, increased blood creatine phosphokinase at 11.0% versus 8.0%, nasopharyngitis at 10.5% versus 9.5%, COVID-19 at 6.0% versus 5.0%, decreased lymphocyte count at 6.3% versus 1.5%, and headache at 5.5% versus 5.0%.
Treatment-emergent serious adverse events remained relatively uncommon. In TRANQUILLO 2, serious adverse events were reported in 3.4% of patients in both the LITFULO 100 mg and placebo groups. In TRANQUILLO, serious adverse events occurred in 2.0% of patients receiving LITFULO 50 mg compared with 2.5% receiving placebo.
Large Phase 3 Program Included More Than 2,000 Patients
The TRANQUILLO clinical development program consists of two pivotal Phase 3 studies, TRANQUILLO 2 and TRANQUILLO, as well as a long-term extension study known as TRANQUILLO LTE.
Together, TRANQUILLO 2 and TRANQUILLO enrolled 2,174 patients with NSV across 271 sites worldwide.
TRANQUILLO 2 evaluated 100 mg of LITFULO administered once daily in 1,567 adults. The study also included an assessment of the 50 mg dose, although Pfizer described that component as exploratory and descriptive.
TRANQUILLO evaluated 50 mg of LITFULO once daily in 607 patients aged 12 years and older. Patients who completed treatment in the parent TRANQUILLO study could subsequently enter the long-term extension program.
For the U.S. studies, the co-primary endpoints were the proportions of patients achieving F-VASI75 and T-VASI50 at Week 52.
Outside the United States, F-VASI75 at Week 52 served as the primary endpoint, while T-VASI50 at Week 52 was designated as a key secondary endpoint.
The size of the program provides a substantial clinical data set for evaluating the potential efficacy, safety and patient experience associated with oral ritlecitinib in NSV.
Exploring a Systemic Approach to Vitiligo
The development program reflects Pfizer’s broader interest in targeting immune-mediated dermatologic diseases through systemic therapies.
Ritlecitinib has dual selectivity for Janus kinase 3 (JAK3) and the TEC family of kinases. These signaling pathways play roles in immune-cell activity. Pfizer’s development strategy is based on the potential for modulation of these pathways to affect immune mechanisms associated with conditions such as vitiligo.
Iltefat Hamzavi, M.D., senior staff physician in the Department of Dermatology at Henry Ford Health and Hamzavi Dermatology Specialists, highlighted the broader burden of NSV.
According to Hamzavi, vitiligo is a chronic autoimmune disease that can affect patients beyond the visible changes in skin pigmentation. He noted that the condition can progress unpredictably and may affect highly visible parts of the body.
Hamzavi said the Phase 3 findings showed significant improvements in facial and total-body repigmentation as well as greater disease stabilization compared with placebo, supporting continued evaluation of LITFULO as a potential systemic treatment option.
LITFULO Builds on Pfizer’s Dermatology Portfolio
LITFULO is already approved by the FDA for the treatment of severe alopecia areata in adults and adolescents aged 12 years and older. The new vitiligo findings expand Pfizer’s investigation of ritlecitinib into another immune-mediated dermatologic condition.
At the 35th EADV Annual Congress, Pfizer presented more than 30 accepted abstracts spanning nonsegmental vitiligo, alopecia areata and atopic dermatitis.
In alopecia areata, the company presented long-term Phase 3 findings showing clinically meaningful scalp hair regrowth with LITFULO through five years. Pfizer reported that no new safety signals were observed in the long-term analysis. The company has also initiated a pivotal study evaluating LITFULO in moderate alopecia areata.
Pfizer’s atopic dermatitis program included a late-breaking exploratory analysis of serum protein biomarkers from the Phase 3 JADE COMPARE study evaluating CIBINQO® (abrocitinib). The company also presented a final integrated safety analysis covering 3,850 patients with up to 6.5 years of exposure.
In addition, Pfizer presented interim Week 16 Phase 2 efficacy and safety findings for tilrekimig (PF-07275315), an investigational trispecific antibody designed to target IL-4, IL-13 and thymic stromal lymphopoietin (TSLP).
Next Steps Toward Regulatory Review
The positive Phase 3 findings from TRANQUILLO 2 and TRANQUILLO mark an important stage in Pfizer’s development of LITFULO for NSV. The company intends to submit the data to regulatory authorities globally, including the FDA and EMA.
If reviewed and supported by regulators, the data could contribute to discussions around systemic treatment strategies for people with NSV. The current findings provide evidence across several dimensions of disease management, including facial repigmentation, total-body repigmentation, patient-reported severity, disease noticeability and stabilization.
For Pfizer, the results also extend the clinical development story of ritlecitinib beyond alopecia areata and into another chronic immune-mediated skin disease. The company’s ongoing dermatology research program continues to investigate how targeted immune modulation may address diseases in which abnormal immune activity contributes to skin changes and disease progression.
The TRANQUILLO 2 and TRANQUILLO results therefore add a substantial new body of Phase 3 evidence to the development of LITFULO in nonsegmental vitiligo, while the planned global regulatory submissions will determine the next stage of the medicine’s potential development in this indication.
About Nonsegmental Vitiligo
NSV is a chronic autoimmune disease in which the immune system attacks melanin-producing cells, leading to a loss of pigment and resulting in white macules and patches on the skin/hair over time.4 NSV can appear at any age and in all skin types, causing depigmentation anywhere on the skin, often affecting highly visible areas such as the face, neck, and hands.1
While vitiligo is frequently treated as a cosmetic condition, it is a serious autoimmune disease that can have a considerable impact on patients’ lives well beyond the physical symptoms.1,2 Because NSV is a chronic disease, systemic treatment options may be needed to help patients restore skin pigmentation and maintain repigmentation over time.3
For more information on Pfizer’s Commitment to Immunology and Inflammation, please visit: Inflammation & Immunology | Pfizer.
For more information on LITFULO and the Phase 3 results in NSV, please visit: Pfizer Announces Positive Topline Phase 3 Results for LITFULO in Patients with Nonsegmental Vitiligo | Pfizer
About LITFULO® (ritlecitinib)
LITFULO is an oral inhibitor of Janus kinase 3 (JAK3) and the TEC family kinases which is being investigated for the treatment of nonsegmental vitiligo. By targeting key immune signaling pathways involved in the disease, LITFULO is thought to modulate the activity of immune cells that contribute to melanocyte destruction.
LITFULO is currently approved for the treatment of severe alopecia areata in adults and adolescents 12 years and older, where it targets the underlying immune mechanisms that drive hair follicle damage and hair loss. Through its dual mechanism, LITFULO has demonstrated the potential to address immune-mediated pathology underlying both alopecia areata and nonsegmental vitiligo.
LITFULO is approved for the treatment of severe alopecia areata in adults and adolescents 12 years and older in the United States, European Union, Canada, Japan, China, and United Kingdom.
The LITFULO development program spans multiple immune‑mediated dermatologic conditions, including alopecia areata, nonsegmental vitiligo, chronic spontaneous urticaria, and hidradenitis suppurativa, supporting a focused development approach in dermatology.