Systemic treatment in vitiligo: EADV 2026 insights from the Tranquillo program
VIDEO
Iltefat Hamzavi (Henry Ford Hospital, Detroit, Michigan, USA) discusses findings from the phase 3 Tranquillo clinical program evaluating ritlecitinib in non-segmental vitiligo, including efficacy and safety findings, disease stabilization, the potential role of systemic treatment, and remaining unmet needs in vitiligo care. View transcript .
Chapters
00:00 What is the Tranquillo clinical program, and why is it important in vitiligo?
VITILIGO RESOURCES
EADV 2026: Iltefat Hamzavi interview transcript
So, ritlecitinib is a medication that's being studied in a specific program called Tranquillo, and Tranquillo has a couple of units to it. So, Tranquillo is a study in which we're using placebo, then we have 50 mg of ritlecitinib. And then Tranquillo 2 is placebo with 50 mg of ritlecitinib as well as a 100 mg arm of ritlecitinib, and then there'll be subsequent other extensions, an open-label extension that will be coming up, but these are the two studies that are being presented at the EADV. This is one of the largest studies that's ever been done in this disease state. So, in Tranquillo 1, there were 401 patients in the active drug arm, 202 in the placebo. In Tranquillo 2, there were approximately another thousand patients in the 50, 100, and placebo arms. And so you have almost 1,600 patients in these studies, which is the largest cohort, to my knowledge, of randomized control studies in the vitiligo community. The study also has the largest number of patients that have been studied in a randomized control trial for patients three and up. And this is going to be important because, as you know, diseases tend to be heterogeneous. If you don't have a large sample size, it's hard to understand how well the medication or the intervention works in different groups. It also gives you confidence that if there are positive or negative results, but especially if there are positive results, how are they likely to happen? And if they're negative results, again, how likely is that to be real? So, the study is designed to pick up whether or not there's a dose ranging effect, is designed to also determine if there's different breakdowns in different subgroups. It also gives you confidence that the results are consistent with what is actually happening. And the other component is the study was done for 52 weeks, which is a very difficult thing to ask our patient community who deal with this condition since it has such a tremendous psychosocial component. But many patients were committed to the study and they completed the 52 weeks, and that duration is designed for vitiligo studies because it takes a long time to see the benefits of interventions with vitiligo. So, a large study randomized controlled with dose ranging, one of the largest that I know of that's been done in this particular area.
So, the results for Tranquillo 1 and Tranquillo 2 showed that the placebo response was consistent across the different arms of about 1.98 to 2.5 approximately on the placebo side and the F-VASI75, the percent of people who achieved 75% improvement on the VASI score on the face, was 12.47 on the Tranquillo 1. And then on Tranquillo 2, there's two arms. The 50 mg arm had a 19% improvement, and the 100 mg arm had a 22% improvement. So, both arms showed improvement. And then when you look at the total VASI, what percent of people achieved a 50% improvement, again, all arms showed significance and there was a difference between the active drug and the placebo. And in Tranquillo 1, which is a 50 mg arm, there was approximately 9% improvement in the T-VASI. I think 9% of people achieved T-VASI50. And in Tranquillo 2, the 50 mg did a little bit better with approximately 13% improvement as a percentage of the population that achieved T-VASI50, and then T-VASI50 on the 100 mg was a little bit higher at 13%. So, Tranquillo 1, 2 showed a significant difference between placebo and active drug, and then the dose dependent effect was greatest in the F-VASI where the 100 mg seemed to outperform the 50 mg and provided a larger percentage of people who achieved F-VASI75. So, that's in line with what we're seeing with other oral studies. We have a percentage of people who respond, and one of the things about vitiligo as we explained earlier, you're damaging melanocytes, which are neural crest–derived cells, they only turn over every 6 months. And what you found is that you don't see much improvement until 12 weeks but then the degree of improvement in the VASI starts to accelerate and it continues to accelerate through week 52. So, it takes 12 to 24 weeks to see much improvement, but then the improvement keeps on getting better. And these study designs, it's hard to go past 52 weeks, but they were able to show in the study that the facial VASI improved compared to placebo, the T-VASI improved compared to placebo. So, you have an improvement. It doesn't start happening until about 3 months. And then you start seeing greater and faster degrees of repigmentation. The other important finding in this population or in this study was the degree of stabilization. In Tranquillo 1, if you look at the active drug arm, you had almost 74% of patients not develop any additional lesions. And on Tranquillo 2, it was approximately 76%. And when you look at the placebo response, it's about 59% developed stabilization where they had no new lesions. And then you had a similar number for Tranquillo 2. So that's almost a 15 to 20% difference between the two groups. When you look at the placebo response on stabilization, it was much more likely that individuals would get worse when they're on placebo. And the percent was significant, and it was significant in both Tranquillo 1 and 2. Why is that important? Because if you're going to take a systemic agent, you are automatically in these studies going to have more than 10% body surface area, which is greater than some of the topical studies. It's also important because these patients tend to have more severe disease. They have more activity, and activity is just a marker of new lesions. Stability is actually developing new lesions. The fact that they were able to measure that there was a significant difference between the placebo and the active drug suggests that the disease stabilizes.
You also were able to show in the side effect profile that was reviewed in this particular presentation that the side effects that you're concerned about, infections or malignancies, were not much higher than placebo. Serious adverse events specifically leading to death were only two events, and they were not related to the medication. And then there were other significant side effects, which involved individuals who had a higher rate of zoster. There's also some paresthesias and some headaches that are present. You also saw a higher risk of nasopharyngitis and upper respiratory infections. So, no significant safety signals were picked up, and the medication overall was very well tolerated. When you compared placebo to active drug, the number of patients who were discontinuing the medication due to side effects was about 1.5%. In placebo, it was about 1% in Tranquillo 2. In Tranquillo 1, placebo actually had a higher dropout rate, 5.5% compared to the active drug, which was 2.3. The one area that seemed to be a little bit higher that is something I should be aware of is herpes zoster, which seems to be higher, about 1.6% in the active drug and 0.5% in the placebo. In JAK inhibitor categories, we're always trying to watch out for MACE events. There were no MACE events in the study at a higher rate than placebo. The two deaths that occurred were explained and not seem to be associated with the medication and associated with other chronic health conditions, and we didn't see higher rates of any malignancies or infections.
And one of the key findings is that the condition of vitiligo is stabilized by using a medication like ritlecitinib at a much higher rate than placebo, which is one of the goals. One of the key goals of therapy is to try to keep it from getting worse. So, the study showed in probably the largest sample size that we've seen so far that the medication ritlecitinib works to help stabilize vitiligo and also repigment the face and the torso, and the side effect profile was well within what we've seen so far with other studies involving JAK inhibitors, and hopeful that this type of information will be helpful to our vitiligo community.
When we look at the unmet needs of individuals with vitiligo, there are extensive unmet needs. One is we need medications to work faster. We also need to prove that medications work over time. And one of the biggest unmet needs is the ability to stabilize the condition so that we don't have to spend months to years trying to repigment with natural course of time or phototherapy. Well, this was one of the largest studies to show that you can stabilize with these agents and you also have safety concerns about using medications chronically in overall healthy individuals. And we did not see any significant safety signals with this medication. And so there's some big gaps that have been addressed, but we have additional gaps, which is speed and also assessing duration of response. But we're very excited about the stabilization data. We've never seen data that I'm familiar with to show this degree of stabilization. And it's also a concept that's evolving, but it's going to take time. And we have to make that go faster without compromising safety.
