Data from two separate phase 2 trials presented at the annual meeting of the European Academy of Dermatology and Venereology suggest that two more Janus kinase (JAK) inhibitors are showing promise for the treatment of nonsegmental vitiligo.
The 52-week results of a phase 2b dose-ranging study with the oral investigational JAK1 inhibitor povorcitinib showed that substantial facial and total body repigmentation could be achieved.
The percentage change from baseline to Week 52 in the Facial Vitiligo Area Scoring Index (F-VASI) and total body VASI (T-VASI) were around 64% and 41%, respectively, depending on the dose of povorcitinib used. Corresponding results in the placebo arm of the trial were about 55% for F-VASI and 18% for T-VASI. The higher the percentage change the greater the degree of repigmentation achieved.
Then, in the phase 2 BARVIT study, oral baricitinib combined with narrowband ultraviolet B (NB-UVB) showed “clinically meaningful superiority” to placebo combined with this type of phototherapy.
After 36 weeks of treatment there was about a 65% change from the baseline F-VASI score and a 45% change in T-VASI score in the baricitinib and phototherapy-treated patients. Corresponding values in the placebo arm were about -4% and 9% in the F-VASI and T-VASI scores.
If the trials’ findings are validated by future studies, it could mean that povorcitinib and baricitinib will join the cream formulation of the JAK1/2 inhibitor ruxolitinib (Opzelura) as a possible treatment for nonsegmental vitiligo. Currently, topical ruxolitinib is the only JAK inhibitor approved for this indication, having gained its licenses from the US Food and Drug Administration in July 2022 and the European Medicines Agency in April of this year.
Active Area of Research
“We have so much development now in vitiligo,” Reinhart Speeckaert, MD, PhD, of Ghent University Hospital in Belgium, said at the meeting. Multiple JAK inhibitors are being tested in vitiligo, including ongoing or planned phase 3 trials with the JAK1 inhibitor upadacitinib (Rinvoq) and the JAK3 inhibitor ritlecitinib (Litfulo).
Speeckaert, who was not involved in either study, told Medscape Medical News that these new data on povorcitinib and baricitinib were both “impressive” in patients with extensive vitiligo.
Discussing povorcitinib first, Speeckaert noted: “It seems that the amount of repigmentation increases steadily with the duration of the treatment. This offers a lot of hope that povorcitinib can result in unprecedented efficacy for vitiligo.”
As for the baricitinib-NB-UVB combination, he said that “a clear difference was seen in the amount of repigmentation” between the combination of baricitinib with NB-UVB and NB-UVB alone.
With 90% repigmentation of the face seen in 50% of patients after 36 weeks, Speeckaert added that these were indeed “remarkable results, and some of the best ever reported.”
The Povorcitinib Phase 2b Study
Khaled Ezzedine, MD, PhD, of Henri Mondor Hospital and Université Paris-Est Créteil Val de Marne in Paris, France, presented the povorcitinib data at the meeting.
In the trial, 171 patients with nonsegmental vitiligo affecting at least 0.5% of their face or 8% of their total body area were recruited and randomly assigned to one of four once-daily oral treatment arms: povorcitinib 15 mg (43 patients), 45 mg (43), or 75 mg (42), or placebo (43). Treatment was for 24 weeks initially.
This was followed by a 24-week extension period where patients in the povorcitinib 45 mg and 75 mg groups continued treatment with those doses and patients in the placebo and 15 mg groups were treated with povorcitinib 75 mg. Treatment was then stopped, with a further 24 weeks of follow-up.
Ezzedine pointed out there were no significant differences in baseline characteristics between the treatment groups: The median age was 50 years, with 77% White, 5% Black, 8% Asian, and 19% Hispanic origin. The mean disease duration was 19.4 years.
The primary efficacy endpoint was the percentage change in T-VASI from baseline to Week 24. Compared with placebo where there was about a -2% change, all doses of povorcitinib resulted in significant improvements in T-VASI, with changes of around 19%, 18%, and 16% for the 15, 45, and 75 mg doses, respectively.
The respective 52-week results for the placebo to 75 mg, 15 to 75 mg, 45 mg, and 75 mg groups were about 18%, 41%, 43%, and 42%.
“Even at week 52, we still haven’t reached the plateau, this is something very interesting,” said Ezzedine.
As for the percentage change from baseline in F-VASI, one of several key secondary endpoints, results at the end of the 24-week phase for the placebo, povorcitinib 15 mg, 45 mg, and 75 mg groups, were respective increases of about 5%, 28%, 36%, and 29%, from baseline. At 52 weeks they were 55% and 64% for each of the povorcitinib groups.
The 24-week T-VASI-50 results were 3% for placebo, and about 11%, 15%, and 6%, for the povorcitinib 15, 45, and 75 mg doses, respectively. And, at 52 weeks, these were about a respective 15%, 45%, 37%, and 38%.
Corresponding F-VASI-50 results were about 9%, 18%, 46%, and 28% at 24 weeks, and 64%, 71%, 78%, and 69% at 52 weeks.
Similar results were seen for F-VASI-75, with the plateau for the benefit not reached at 52 weeks’ treatment with povorcitinib.
“The durability of response was demonstrated during the 24-week post-treatment period, with maintenance of not only the total VASI but also the F-VASI scores,” Ezzedine said, noting that this finding needed to be confirmed in a larger patient population.
At week 52, nearly 90% of those on povorcitinib 45 mg or 75 mg had a treatment-emergent adverse event, which included COVID-19 (36.1%), blood creatinine phosphokinase increase (13.3%), acne (12%), fatigue (10.8%), and headache (9.6%); 2.4% experienced a serious adverse event, but none were considered related to treatment.
On X (formerly Twitter), Zenas Yiu, MBChB, MRCP (Dermatology), of the University of Manchester, UK, observed that it was “hard to interpret the extension data given the as-observed analyses and low sample size at later timepoints.” Yiu also noted that the povorcitinib data were “interesting to hear” and that the drug “looks promising” in vitiligo.
Baricitinib With NB-UVB
Also looking promising was the combination of baricitinib and NB-UVB, as detailed by Julien Seneschal, MD, PhD, of the National Reference Center for Rare Skin Diseases at the University of Bordeaux, France.
“Combination with phototherapy is probably better for the treatment of vitiligo, said Seneschal, who, together with Ezzedine, Speeckaert, and others, is part of an international task force that recently updated recommendations for the diagnosis and treatment of vitiligo.
Speeckaert observed: “As JAK inhibitors reduce the inflammation, they work especially well on reducing disease activity. However, a combination with a treatment that stimulates melanocytes such as NB-UVB may be of particular interest for repigmentation.”
Hence there has been a lot of interest in using phototherapy together with the JAK inhibitors, which is one reason why the BARVIT study was conducted. Essentially it’s a “proof-of-concept” study, Seneschal said.
The trial included 49 patients with active vitiligo, which is important, said Seneschal, as these are the patients who are “at high risk of developing new lesions in the next 3 to 6 months without any treatment.”
The trial ran for 48 weeks, with patients (mean age, 49 years) randomly assigned to an initial 12 weeks’ treatment with either baricitinib (37 patients) or placebo (12 patients) and then to continue their treatment for a further 24 weeks in combination with NB-UVB administered twice a week. There was a final 12-week off-treatment follow-up period.
Baseline characteristics differed slightly between the baricitinib and placebo groups, Seneschal said. Notably, the baseline T-VASI score was lower in the baricitinib than placebo group (17.7% vs. 27%).
The percentage change from baseline in T-VASI scores at week 12, when just baricitinib or placebo had been taken and NB-UVB treatment was about to start, were a respective -5.1% and 0.8%.
After 12 weeks of combined treatment, however, at week 24, percentage changes in T-VASI were about -26% for baricitinib and -5% for placebo plus NB-UVB arm, and by week 36, the corresponding values were about -45% and -9%.
The percentage change from baseline in F-VASI scores were about -47% and -65% in the baricitinib arm and about 59% and 4% in the placebo plus NB-UVB arm at weeks 24 and 36, respectively.
Almost 65% of those in the baricitinib group and about 58% of those in the placebo group had an adverse event, which was not significantly different, nor were serious adverse events (one in the placebo and two in the baricitinib group). One patient in the baricitinib group had a pulmonary embolism.
“Baricitinib stabilized the disease after 3 months of treatment,” Seneschal observed.
“In combination with phototherapy, baricitinib showed a significant level of repigmentation with improvement in the quality of life of patients,” he added.
“We think that phototherapy should be considered in future clinical trials in addition to experimental drugs to induce better and significant repigmentation in patients.”
The phase 2b study of povorcitinib was funded by Incyte Corporation and the BARVIT study was funded by Eli Lilly.
Speeckaert was not involved in either study and has no ties to either company. He has received speaker fees from AbbVie, Almirall, Janssen, Leo Pharma, Novartis, Pfizer and Pierre Fabre, and is the copyright holder of the Vitiligo Extent Score (VES).
Ezzedine disclosed acting as a consultant to Lilly, AbbVie, La Roche-Posay, Pfizer, Pierre Fare, Sanofi, and Viela Bio.
Seneschal has received grants, honoraria, or both from AbbVie, Bristol-Myers Squibb, Calypso Biotech, Eli Lily, Incyte, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi, Sun Pharmaceuticals, and Viela Bio. Seneschal also holds patents on the use of MMP9 inhibitors in depigmenting disorders.
Sara Freeman is a medical journalist based in London, England.
Source: Read Full Article