2024 Vitiligo Breakthroughs

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The year has seen substantial developments in the treatment of vitiligo. Breakthroughs, such as new off-label indications of existing treatments and modernized remedies such as phototherapy, aim to help patients achieve skin repigmentation. From updated diagnosis procedures for pediatric patients to innovative drugs upadacitinib, afamelanotide, and VYN201, these clinical studies and reviews highlight the significant advancements made this year in treating various types of vitiligo.

Upadacitinib Achieves Skin Repigmentation Through Week 52

New data on upadacitinib (UPA) for vitiligo were presented in March at the 2024 American Academy of Dermatology Annual Meeting in San Diego, California. In a phase 2 trial (NCT04927975) evaluating the efficacy and safety of UPA in adults with nonsegmental vitiligo, the study authors found that skin repigmentation as measured by facial Vitiligo Scoring Index (F-VASI) and total (T)–VASI occurred in all UPA-treated patients from week 0 to 24, therefore meeting the primary end point. This continued without plateau through week 52 with achievement of F-VASI75 in 37%/29% of UPA 6 mg (n = 14), 63%/51% of UPA 11 mg (n = 24), 38%/26% of UPA 22 mg (n = 11) and achievement of T-VASI50 in 32%/25% (n = 12), 40%/32% (n = 15), and 41%/28% (n = 12), respectively. Regarding positive perceptions, 77% to 90% of UPA-treated patients reported their vitiligo as “much better” or “a little better” at week 52.¹

Recommendations for Diagnosing and Treating Vitiligo in Young Patients

Experts developed evidence and consensus-based recommendations for the diagnosis and treatment of vitiligo, particularly regarding the use of topical therapeutics, in pediatric, adolescent, and young adult patients. The consensus statement, published in March 2024, fulfills an unmet need, as researchers noted that guidelines for vitiligo have not been updated since 1996 and not at all for pediatric patients. Experts agreed upon a definition of vitiligo, including methods for diagnosis and confirmation of diagnosis. In addition to defining best practices for diagnosis and evaluation, experts noted that it is crucial to consider closer observation for more concerning signs, which may require more aggressive therapy. They also agreed upon the use of topical steroids, topical calcineurin inhibitors, and UV-B light therapy as the standard of care in young patients. Combination therapy, they noted, may enhance the initial repigmentation response in some patients.²

Vyne Therapeutics Initiates Phase 2b Trial of BET Inhibitor VYN201 for Vitiligo

In June 2024, Vyne Therapeutics Inc announced the dosing of the first subject in its phase 2b clinical trial for VYN201, a novel BET inhibitor aimed at treating nonsegmental vitiligo. The trial will assess the safety and efficacy of VYN201, a topical gel administered once daily, in subjects with either active or stable nonsegmental vitiligo. VYN201 targets local treatment, aiming to provide signicant benefits with low systemic exposure. Approximately 160 participants will be enrolled in the study, divided into 4 groups with a 1:1:1:1 ratio. Three groups will receive different concentrations of VYN201 (1%, 2%, or 3%), while the fourth group will receive a vehicle placebo. After the initial 24 weeks, participants in the vehicle group will be randomly reassigned to 1 of the active treatment groups for the remaining 28 weeks.³

Exploring Afamelanotide for Vitiligo: Insights Into the CUV 105 Phase 3 Clinical Trial

The phase 3 CUV 105 trial (NCT06109649) will assess the efficacy and safety of afamelanotide (Scenesse) in combination with phototherapy for the treatment of vitiligo. Tareen Dermatology and pharmaceutical company Clinuvel began recruiting participants at multiple study sites across the US in September 2024. The CUV 105 clinical trial is a phase 3, multicentric, randomized, controlled study designed to evaluate the efficacy and safety of afamelanotide in combination with narrowband ultraviolet B (NB-UVB) phototherapy for treating vitiligo. Its primary objective is to assess whether the combination therapy results in superior repigmentation compared with NB-UVB monotherapy. The study targets patients with Fitzpatrick skin types IV to VI and will utilize VASI to measure repigmentation.⁴

Review Explores Abrocitinib’s Off-Label Uses

An October 2024 review demonstrated the increasing potential of abrocitinib to treat various skin disorders, including vitiligo. Abrocitinib is an oral, small-molecule inhibitor of Janus kinase 1 (JAK1) that manages both local and systemic in ammation and is specically designed for the treatment of moderate to severe atopic dermatitis. According to researchers, the clinical implications of abrocitinib’s selective inhibition of JAK1 remain uncertain. Approved in Europe in 2021 for adults and adolescents 12 years and older, it received FDA approval in January 2022. Given its importance in various in inflammatory and immune-mediated diseases, reports of abrocitinib’s off-label use for other conditions have been limited since its approval. With this in mind, the review aimed to compile these instances to aid clinicians in considering abrocitinib when standard treatments fail. Among the 37 studies, the most frequently documented off-label uses included 12 cases of vitiligo and showed signicant repigmentation.⁵

References

1. Passeron T, Ezzedine K, Hamzavi I, et al. Efficacy and safety after 52 weeks of once-daily upadacitinib in adults with extensive nonsegmental vitiligo (NSV): final results from a phase 2, multicenter, randomized, double-blind, placebo-controlled, doseranging study. Presented at: 2024 American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA.
2. Renert-Yuval Y, Ezzedine K, Grimes P, et al. Expert recommendations on use of topical therapeutics for vitiligo in pediatric, adolescent, and young adult patients. JAMA Dermatol. 2024;160(4):453-461. doi:10.1001/jamadermatol.2024.0021
3. Vyne Therapeutics announces dosing of first subject in phase 2b vitiligo trial of novel BET inhibitor VYN201. Vyne Therapeutics. News release. June 5, 2024. Accessed November 7, 2024. https://vynetherapeutics.com/press-releases/vyne-therapeutics-announcesdosing-of-first-subject-in-phase-2b-vitiligo-trial-of-novel-bet-inhibitor-vyn201/
4. A study to compare the efficacy and safety of SCENESSE and narrow-band ultraviolet (NB-UVB) light versus NB-UVB light alone in patients with vitiligo. ClinicalTrials.gov. Accessed September 5, 2024. https://clinicaltrials.gov/study/NCT06109649?cond=scenesse&aggFilters=status:rec&rank=2
5. Mitroi GG, Mitroi GF, Ic OM, et al. Off-label uses of abrocitinib: Review of emerging therapeutic applications beyond atopic dermatitis. Life (Basel). 2024;14(9):1127. doi:10.3390/life14091127