Ruxolitinib Cream Shows Improved Efficacy, Sustained Safety in Vitiligo After Extended Follow-up

Late-breaking findings presented Saturday at the 2022 American Academy of Dermatology (AAD) Annual Meeting showed ruxolitinib cream (​​Opzelura) monotherapy was associated with clinically significant improvement in facial and total body repigmentation vs vehicle (nonmedicated cream) in the treatment of adolescent and adult patients with nonsegmental vitiligo over 52 weeks.¹

Assessed across 2 phase 3 studies, TRuE-V1 (NCT04052425) and TRuE-V2 (NCT04057573), patients aged 12 and older with a diagnosis of nonsegmental vitiligo and depigmented areas covering less than or equal to 10% total body surface area (BSA) were randomized 2:1 to apply 1.5% ruxolitinib cream twice daily (BID) or vehicle BID.

The 52-week data serves as a 28-week treatment extension of the initial 24-week TRuE-V1 and TRuE-V2 studies, which had shown that a significantly greater proportion of patients given ruxolitinib cream BID achieved the primary and secondary end points vs vehicle BID.

“Vitiligo can have a very high impact on a patient's quality of life. It can carry with it a stigma, and lead to depression, isolation, and affect intimacy. Every patient is affected differently,” said lead abstract author David Rosmarin, MD, vice chair of Research and Education, Department of Dermatology, Tufts Medical Center, in an interview with The American Journal of Managed Care^®.

The findings presented at AAD 2022 showed that positive effects in the primary and secondary end points were achieved in a significantly greater proportion of patients across 52 weeks vs 24 weeks and baseline, with overall safety consistent with previous study data:

• primary end point—approximately 50% of patients achieved greater than or equal to 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75) at 52 weeks, compared with the F-VASI75 improvement from baseline reported for these patients at week 24 (the primary end point of the study), which was 29.9%
• secondary end points—approximately 75% of patients achieved greater than or equal to 50% improvement from baseline in the F-VASI (F-VASI50) and nearly one-third (approximately 30%) achieved greater than or equal to 90% improvement from baseline in the F-VASI (F-VASI90), compared with the week 24 response rates for F-VASI50 and F-VASI 90 of 51% and 15%, respectively
• additional secondary end points were met: a greater proportion of patients at week 52 vs week 24 achieved the secondary end points of greater than or equal to 50% improvement from baseline in total body VASI (T-VASI50), over one-third of patients achieved a Vitiligo Noticeability Scale (VNS) response, and improvement on percentage change from baseline in facial body surface area (F-BSA) was observed at 52 weeks vs 24 weeks

Patients who were switched from vehicle BID to ruxolitinib cream bid for the 28-week treatment extension were also shown to exhibit efficacy data consistent with week 24 data in patients who were randomized to the intervention group from baseline.

No clinically significant application site reactions or serious treatment-related adverse events (AEs) related to ruxolitinib cream were observed.

“This phase 3 program looked at ruxolitinib cream monotherapy on its own and there's potential that when we add in, for instance, phototherapy or other treatments that could be synergistic, we'll see even bigger responses,” noted Rosmarin.

Factors such as skin phenotype and disease duration have been indicated to potentially affect treatment efficacy in patients with vitiligo, and additional abstract findings published Friday explored the efficacy and safety of ruxolitinib cream at 24 weeks across patient demographic and baseline clinical characteritics subgroups.²

Utilizing pooled data of the 2 phase 3 double-blind TRuE-V1 and TRuE-V2 studies, patients with nonsegmental vitiligo (mean [SD] age, 39.6 [15.1]) were stratified by geographic region (North America and Europe) and Fitzpatrick skin phototype (types I–II or types III–VI), and were randomized 2:1 to receive 1.5% ruxolitinib cream BID (n = 450) or vehicle BID (n = 224) for 24 weeks.

The primary end point was the proportion of patients achieving F-VASI75 at week 24, with subgroup analyses investigating F-VASI75 response and safety by patient demographics and baseline clinical characteristics, including age, sex (53.1% female), race (81.9% White), Fitzpatrick skin phototype (67.5% types III–VI ), geographic region, F-BSA, investigator-assessed disease stability, and previous therapy (topical corticosteroid, topical calcineurin inhibitors, phototherapy).

After 24 weeks, F-VASI75 was achieved by a significantly greater proportion of patients applying ruxolitinib cream BID vs vehicle BID (30.7% vs 9.9%; P < .0001), with no substantial differences observed among all subgroups.

Substantive F-VASI75 response rate differences between ruxolitinib cream and vehicle were also shown in all subgroups of patient demographics and baseline clinical characteristics. Rates of AEs and treatment-related AEs were generally similar among demographic subgroups of patients randomized to ruxolitinib cream.

“We see that it is easier to repigment certain anatomical locations, such as the head and neck region. Also, we’re effectively repigmenting the trunk, upper, and lower extremities. The hands and feet tend to be very recalcitrant, and it's a little bit more challenging to treat those areas as well with ruxolitinib cream,” Rosmarin said.

A supplemental New Drug Application for ruxolitinib cream in vitiligo is currently under Priority Review by the FDA, with a Prescription Drug User Fee Act target action date of July 18, 2022. If approved, ruxolitinib cream would be the first and only FDA-approved medical treatment for repigmentation in patients with vitiligo.

References

1. Rosmarin D, Passeron T, Pandya AG, et al. Efficacy and safety of ruxolitinib cream monotherapy for the treatment of vitiligo: Results from two 52-week phase 3 studies. Presented at: 2022 American Academy of Dermatology Annual Meeting. Session: S026–Late-Breaking Research: Clinical Trials.

2. Rosmarin D, Ezzedine K, Desai SR, et al. Efficacy and safety of ruxolitinib cream for the treatment of vitiligo by patient demographics and baseline clinical characteristics: Pooled subgroup analysis from two randomized phase 3 studies. Presented at: 2022 American Academy of Dermatology Annual Meeting. Abstract: 35187.