Emerging Therapeutic for Non-Segmental Vitiligo: Merck’s MK-6194

“It's important for clinicians to recognize the mental burden of vitiligo and how important it is to engage these patients as well as to inform them about the new options,” said Iltefat Hamzavi, MD, in a recent interview with Dermatology Times.

Hamzavi, a board-certified dermatologist at the Henry Ford Health Center and Hamzavi Dermatology in Michigan, and a board member of the Global Vitiligo Foundation, is one of the clinical trial investigators evaluating Merck’s MK-6194 in a global phase 2 trial of non-segmental vitiligo, as well as systemic lupus erythematosus (SLE). REGINA 007 (NCT06113328) is actively recruiting patients for its non-segmental vitiligo trial at sites across the US, Argentia, Australia, Belgium, Canada, Chile, Colombia, France, Germany, Israel, Japan, Korea, Mexico, Netherlands, Spain, Switzerland, and the UK.¹

Inclusion criteria of REGINA 007 include a clinical diagnosis of non-segmental vitiligo, disease duration of at least 6 months, an F-VASI score of ≥ 0.3 at screening and baseline, a BSA of ≥0.3% at screening and baseline, a T-VASI score of ≥4 at screening and baseline, and total body vitiligo area ≥4% at screening and baseline excluding hands and feet involvement.¹

As a trial investigator and vitiligo expert, Hamzavi discusses an overview of the REGINA trials, the significance of MK-6194 being developed for non-segmental vitiligo and SLE, MK-6194 as an IL-2M and how it compares to other therapies, key end points, how clinicians can enroll their patients, and the importance of remembering the psychological burden of vitiligo on patients.

Key Highlights

1. REGINA Trial Overview

Hamzavi: Both SLE and vitiligo are autoimmune diseases, and they involve defects in the T cells. And there are different ways to hopefully rebalance T cell activity. One is to suppress it and suppress various targets, such as JAK inhibitors will suppress certain cytokines that will stimulate T cell formation. There's also another approach, which is to boost the regulatory T cell function. T cells are regulated by a set of processes that involve a variety of interleukins, interleukin-2 specifically, and it allows for the increased functioning of regulatory T cells. So rather than suppressing certain T cell functions, you hopefully want to bring the immune system back into balance with regulatory T cells, increasing their activity and boosting their activity and then reducing the clinical impact of diseases like SLE and vitiligo. The specific trial that we're looking at, the REGINA trial, is attempting to see if modification of the regulatory T cells will improve the overall clinical response.

2. SLE as a Comorbidity of Vitiligo

Hamzavi: When you look at the genome-wide associated surveys, you'll find that the rates of vitiligo as well as SLE are present in both gene profiles. So, when you have molecular evidence with the gene profiles, you have clinical evidence, and it makes sense to see if medications can be used for both diseases. Lastly, it makes sense from a development perspective to have one drug treat multiple diseases. Then we slowly understand that the pathways for different diseases are shared, and that will allow us to group development.

3. IL-2M Mechanism of Action

Hamzavi: The IL 2M cytokines affect regulatory T cells. So, it's different in that we don't expect to see theoretically some of the side effects of some of the other inhibitors that affect the immune system. Rather than suppressing T cell function, you're increasing T cell function, but the T cell function you're increasing is a regulatory function so that you don't have the autoimmune events. We anticipate the side effect profiles will hopefully be improved, and hopefully the results will also be better in the sense that more people respond. Secondly, it'll have a greater depth of response, meaning that the degree of response will be greater than the people who do response medication. Because right now, we don't exactly know which medication works best in individuals and not all individuals respond to the degree that patients want, which in vitiligo is at least an 80% degree of improvement in the outcome measure called the VASI.

4. Key End Points

Hamzavi: The primary end point for all of these is patient well-being, so patient-reported outcomes. People don't come to the care of a dermatologist for morbidity issues, these diseases, very rarely will cause death, but they cause significant morbidity. And when I say morbidity, what I mean, specifically in vitiligo, is the rates of depression and reductions of quality of life are pretty significant. In one of the recent papers, as published in JAMA as well as another one in BJD, it showed that anywhere from 60% to 90% of patients had a PHQ9 of 2, which are the level of depression patients with vitiligo. A large percentage of individuals with vitiligo end up developing depression, and the population in one of the studies, about 25% of individuals were on some form of antidepressant medication, and the levels of depression were higher in younger individuals, individuals with spatial vitiligo, individuals with darker skin, individuals with leg on their hands. And so, the measure of success has to be a measure of well-being.

5. How to Enroll Patients

Hamzavi: We're looking for individuals who have more than about half a percent, so half a palm of vitiligo that was completely depigmented. So, if you only have a few spots on the face, it's harder to enroll those patients because the FDA, as well as other trials, have required that you have that severity of vitiligo. So, you have to have a little bit more on the face. Secondly, you have to have some involvement on the torso. And then, just to remind your readers, there are 2 types of vitiligo, there's non-segmental and segmental, so it's only in one half the body. Those patients are not eligible for the study. The study is only studying non-segmental vitiligo, which is more of an immunologically based form of vitiligo.

6. Advice for Clinicians

Hamzavi: It's important for clinicians to recognize the mental burden of vitiligo and how important it is to engage these patients as well as to inform them about the new options. We have things that work today, but we have to get much better, and unless we make these breakthroughs, then we're not going to be able to best care these individuals. And lastly, any form of vitiligo treatment that we have to date or even in the near future, takes time, so these trials will be at least a year to see significant improvement, so it's going to take longer than we expect to see with an atopic dermatitis or psoriasis study.

Reference

A clinical study of MK-6194 for the treatment of vitiligo (MK-6194-007). Clinicaltrials.gov. Updated July 19, 2024. Accessed July 26, 2024. https://clinicaltrials.gov/study/NCT06113328#contacts-and-locations