Pfizer Inc. (NYSE: PFE) today presented results from two Phase 3 trials evaluating the efficacy and safety of LITFULO® (ritlecitinib) as a once-daily oral treatment across a wide range of disease extent.
In the two studies, TRANQUILLO 2 and TRANQUILLO, LITFULO 100 mg and 50 mg, respectively, significantly improved facial and total body repigmentation compared to placebo. These improvements were supported by patient-reported outcomes indicating reduced disease severity and meaningful change in facial and total body vitiligo, as well as greater disease stabilization compared to placebo. These results from the largest Phase 3 program to date evaluating an oral systemic therapy for nonsegmental vitiligo (NSV) were presented today in a late-breaking oral presentation at the 35th European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria.
Pfizer intends to submit these data to regulatory authorities globally, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for review.
"LITFULO has dual selectivity for JAK3 and the TEC family kinases, signals that immune cells use to attack pigment-producing cells in the skin, so it addresses a root cause of nonsegmental vitiligo rather than its visible effects alone. Across the largest Phase 3 program to date evaluating an oral systemic therapy for nonsegmental vitiligo, both TRANQUILLO 2 and TRANQUILLO demonstrated strong and increasing improvements in facial and total body repigmentation over time and also improved patients' own perception of facial and overall disease severity. We look forward to discussing these results with regulators to bring this potential option to patients as soon as possible."
- Michael Vincent, M.D., Ph.D., Chief Inflammation & Immunology Officer, Pfizer
"Nonsegmental vitiligo is a disease that can have a substantial burden on patients' lives beyond the visible symptoms on their skin. 1,2,3 It is a chronic autoimmune disease, yet patients often face stigma because it is trivialized as a condition that affects only skin appearance. 2 It can progress unpredictably, often across highly visible areas, and for decades people living with vitiligo have relied on limited available treatment options. 2,3 Research has shown that LITFULO (ritlecitinib) not only significantly improved facial and total body repigmentation, but also resulted in greater disease stabilization compared to the placebo. 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."
- Iltefat Hamzavi, M.D., Senior Staff Physician, Department of Dermatology, Henry Ford Health and Hamzavi Dermatology Specialists
Key Results from TRANQUILLO Studies
- Co-primary Endpoints -data presented from the TRANQUILLO 2 (100 mg LITFULO) and TRANQUILLO (50 mg LITFULO) studies, respectively :
- 21.86% and 12.47% of patients taking LITFULO achieved F-VASI75 (≥75% improvement in Facial Vitiligo Area Scoring Index) compared to 2.40% and 2.48% on placebo, respectively.
- 13.02% and 8.98% of patients taking LITFULO achieved T-VASI50 (≥50% improvement in Total Vitiligo Area Scoring Index) compared to 2.40% and 1.98% on placebo, respectively.
- Key Secondary Endpoints: LITFULO achieved statistically significant and clinically meaningful improvements compared to placebo across multiple measures of facial and total body repigmentation. Across both trials, significant improvements from baseline in F-VASI and T-VASI were seen as early as Week 24 and increased through Week 36 and Week 52 compared to placebo. Additionally, more patients on LITFULO achieved clinically meaningful improvements at earlier timepoints, as measured by F-VASI75 and T-VASI50 at Week 24 and Week 36 compared to placebo. LITFULO also significantly reduced patient-reported facial and overall disease severity compared to placebo at Week 52.
- Other Selected Endpoints (not type I error controlled): Patients on LITFULO also reported benefit over placebo based on meaningful change in patient global impression of change in face (PGIC-F) and overall vitiligo (PGIC-V) vs placebo. Noticeability (VNS) improved through Week 52 with more patients rating their vitiligo as "a lot less" or "no longer" noticeable compared to placebo. Treatment with ritlecitinib, at both dose levels, resulted in greater disease stabilization compared with placebo from Week 24 onward, with maintained stabilization through Week 52. In an assessment of 50 mg LITFULO in TRANQUILLO 2, clinically meaningful improvement over placebo was observed for both F-VASI75 and T-VASI50 at Week 52.
- Safety: The safety profile of LITFULO in NSV was consistent with the established safety profile in alopecia areata. No new safety signals were observed. Overall, the proportion of patients with treatment‑emergent adverse events (TEAEs) was similar across all treatment groups.
- In TRANQUILLO 2, a TEAE was reported in 67.7% or 62.0% of patients treated with LITFULO 100 mg or placebo, respectively. The most common TEAEs were upper respiratory tract infection (8.9% vs. 3.4%), nasopharyngitis (7.9% vs. 7.3%), and headache (4.0% vs. 5.4%).
- In TRANQUILLO, a TEAE was reported in 81.0% or 77.1% of patients treated with LITFULO 50 mg or placebo, respectively. The most common TEAEs were upper respiratory tract infection (14.0% vs. 10.9%), increased blood creatine phosphokinase (11.0% vs. 8.0%), nasopharyngitis (10.5% vs. 9.5%), COVID-19 (6.0% vs. 5.0%), decreased lymphocyte count (6.3% vs. 1.5%), and headache (5.5% vs. 5.0%).
- Treatment-emergent serious AEs (TESAEs) were reported in a low number of patients across both studies: 3.4% or 3.4% in TRANQUILLO 2 for those on LITFULO 100 mg or placebo, respectively; 2.0% or 2.5% in TRANQUILLO for those on LITFULO 50 mg or placebo, respectively.
Phase 3 Clinical Trial Designs for TRANQUILLO 2 and TRANQUILLO
- The Phase 3 TRANQUILLO clinical development program consists of two pivotal trials - TRANQUILLO 2 and TRANQUILLO - and a long-term extension trial, TRANQUILLO LTE.
- TRANQUILLO 2 and TRANQUILLO evaluated 2,174 patients in total with NSV across 271 sites worldwide.
- TRANQUILLO 2: Evaluated 100 mg LITFULO once daily in 1,567 adults. The study also included an assessment of 50 mg LITFULO that is exploratory and descriptive in nature.
- TRANQUILLO: Evaluated 50 mg LITFULO once daily in 607 patients aged 12 years and older.
- Patients enrolled in the TRANQUILLO LTE completed treatment in the parent study, TRANQUILLO.
- Endpoints: For both studies in the U.S., the co-primary endpoints were the proportion of patients who achieved F-VASI75 and the proportion of patients who achieved T-VASI50 at Week 52.
- In countries outside of the U.S., F-VASI75 at Week 52 was the primary endpoint and T-VASI50 at Week 52 was a key secondary endpoint.
Advancing Pfizer's Commitment to Immune-Mediated Dermatologic Conditions
These results for LITFULO highlight the medicine's potential for people living with NSV and build on Pfizer's longstanding commitment to immune-mediated dermatologic conditions. LITFULO is currently approved by the FDA for the treatment of severe alopecia areata in adults and adolescents 12 years and older.
The positive results for LITFULO in vitiligo further reinforce the potential value of inhibiting the JAK3 and TEC family kinases across multiple immune-mediated skin diseases and may position it to be a new oral systemic therapy option for adults with NSV.
Pfizer is presenting more than 30 accepted abstracts across its dermatology portfolio at the 35th EADV Congress, spanning nonsegmental vitiligo, alopecia areata, and atopic dermatitis.
- In alopecia areata, Pfizer presented long-term Phase 3 data showing clinically meaningful improvements in scalp hair regrowth with LITFULO (ritlecitinib) through five years, with no new safety signals observed. Pfizer has also initiated a pivotal study evaluating LITFULO for the treatment of moderate alopecia areata.
- In atopic dermatitis, Pfizer presented a late-breaking exploratory analysis of serum protein biomarkers from the Phase 3 JADE COMPARE study of CIBINQO (abrocitinib), alongside a final integrated safety analysis of 3,850 patients with up to 6.5 years of exposure. Pfizer also presented interim Phase 2 efficacy and safety results at Week 16 for tilrekimig (PF-07275315), an investigational, potential first-in-class trispecific antibody targeting IL-4, IL-13, and TSLP.
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
