Two pivotal phase 3 trials found the oral JAK3/TEC inhibitor significantly improved both facial and total body repigmentation at one year.
An oral systemic therapy could soon expand the treatment landscape for nonsegmental vitiligo after Pfizer announced positive topline results from the largest phase 3 clinical program ever conducted for the autoimmune skin disease.
The company said both the TRANQUILLO and TRANQUILLO 2 studies met all co-primary efficacy endpoints, with once daily ritlecitinib producing statistically significant and clinically meaningful improvements in facial and total body repigmentation compared with placebo after 52 weeks of treatment.
Pfizer said in a statement it planned to pursue global regulatory submissions seeking approval for the drug in adults with nonsegmental vitiligo.
The studies evaluated ritlecitinib (Litfulo), an oral inhibitor of Janus kinase 3 (JAK3) and TEC family kinases, in patients with both active and stable nonsegmental vitiligo across a broad spectrum of disease severity.
TRANQUILLO enrolled 607 adults and adolescents aged 12 years and older receiving 50mg daily, while TRANQUILLO 2 enrolled 1567 adults randomised to either 50mg or 100mg daily, bringing the total study population to 2174 patients treated across 271 sites worldwide.
Across both trials, significantly more patients receiving ritlecitinib achieved at least a 75% improvement from baseline in the Facial Vitiligo Area Scoring Index (F-VASI75) and at least a 50% improvement in the Total Vitiligo Area Scoring Index (T-VASI50) compared with placebo at Week 52.
In the United States these measures were the co-primary endpoints, while outside the US F-VASI75 served as the primary endpoint and T-VASI50 as a key secondary endpoint.
The researchers said the findings were notable because vitiligo remained one of the few common inflammatory skin diseases with limited systemic treatment options despite affecting an estimated 0.5-2% of the global population.
The chronic autoimmune condition results from immune-mediated destruction of melanocytes, leading to progressive depigmented patches that frequently involve highly visible areas such as the face, hands, and neck.
Although often dismissed as cosmetic, vitiligo is associated with substantial psychosocial burden, reduced quality of life, and stigma.
Pfizer’s chief inflammation and immunology officer, Dr Michael Vincent, said the results reinforced the company’s confidence that ritlecitinib could become a new oral systemic option capable of restoring and maintaining pigmentation in patients whose disease warranted more than local therapy.
“Litfulo was internally discovered by Pfizer and has a unique mechanism of action targeting TEC family kinases and JAK3, giving rise to its distinct clinical profile,” he said.
“The positive results from the TRANQUILLO pivotal studies in nonsegmental vitiligo build on our deep expertise in dermatology and on our experience with Litfulo in severe alopecia areata, including its established efficacy and well-characterized safety profile.
“These findings give us confidence that, if approved, Litfulo could become a new oral systemic treatment option for adults living with NSV, significantly improving and potentially maintaining facial and total body repigmentation.”
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Vitiligo specialist Dr Iltefat Hamzavi, a senior staff physician at Henry Ford Health’s Department of Dermatology, said many patients continued to struggle with the unpredictable nature of the disease and the limitations of currently available treatments.
“Living with nonsegmental vitiligo can have a profound impact on patients’ daily lives,” he said.
“Many patients experience frustration due to the unpredictable nature of nonsegmental vitiligo as well as the limitations of currently available treatments and are seeking additional options that can address the underlying disease.”
He said the degree of facial and total body repigmentation seen in the studies supported the potential for systemic therapy to change the treatment paradigm for patients whose disease burden extends beyond what can reasonably be managed with topical therapies or localised treatment alone.
The safety profile observed in the vitiligo studies was consistent with the established experience of ritlecitinib in severe alopecia areata, Pfizer reported. No new safety signals emerged and the overall rate of treatment-emergent adverse events was similar across active treatment and placebo groups.
Ritlecitinib is already approved in Australia and multiple international markets for severe alopecia areata in adults and adolescents aged 12 years and older.
The company is also investigating the medicine in chronic spontaneous urticaria and hidradenitis suppurativa as part of a broader dermatology development program.
Detailed efficacy and safety data from the trials are expected to be presented at a future scientific meeting.
