Dr Rosmarin illustrates treatment management of vitiligo with the use of JAK inhibitors.
David Rosmarin, MD: Our JAK inhibitors have shown the most promise. Ruxolitinib cream 1.5% twice a day has gone through 2 phase 3 studies. The PDUFA [Prescription Drug User Fee Act] date is July 18, 2022. The studies show that about half the patients at a year will get 75% or more of their pigment back on the face, and about half the patients at the year mark will get 50% or more of the pigment back on the whole body. That’s what the data are showing for ruxolitinib cream. In terms of safety, it looks promising. It’s already approved for atopic dermatitis as of September 2021. We see about a 6% rate of acne and a 6% rate of application site reaction, itch, or redness, but it generally doesn’t burn or sting. That’s a very promising treatment for patients with vitiligo.
When we look at the subgroup analysis, we see that it doesn’t matter whether patients have had vitiligo for more than 50 years or for a short time. It works across age, gender, and race. We see somewhat similar responses across all those different subgroups. That’s also what we see from the data from ruxolitinib cream. When we look at anatomic regions, the head and neck does the best, trunk and extremities after that, and the acral sites are the least responsive. Nevertheless, we still see a significant benefit of the hands and feet with ruxolitinib cream compared with vehicle.
In terms of some of the other JAK inhibitors in development, ritlecitinib, Pfizer’s JAK3 inhibitor, has completed a phase 2 trial. This study was designed a little differently. It included only patients who had active, progressive vitiligo. About 12% of patients achieved 75% or more repigmentation at the 6-month mark on the highest dose of the medication. We view both an oral and a topical as necessary because an oral might be better for patients who have a large body surface area. The ruxolitinib cream limited the body surface area to 10% or less. With patients who are progressive in nature and getting new spots, it’s hard to keep chasing that with a cream. An oral agent would make more sense, just like using phototherapy. That’s the way we view it. There’s room for both topicals and oral JAK inhibitors, and both will be important to help patients out.
Brett King, MD, PhD: One thing we’ve left out of the conversation is that it isn’t coincidental that we’re talking about JAK inhibitors. This is very deliberate. With JAK inhibitors, the autoimmune [system], the mechanism of disease, the mechanism by which T cells or immune cells attack and destroy the melanocytes, or the color cells, in the skin seems very much to be mediated by a cytokine or a chemical messenger in the body, the messaging of which can be disrupted with a JAK inhibitor. It’s important for everybody to know that this isn’t another case of simply throwing a JAK inhibitor at an autoimmune problem. We have a lot of data to support that this is the right path for this disease.
David Rosmarin, MD: It makes a lot of sense mechanistically. Our typical immunosuppressants don’t work so well on the particular arm in the immune system that’s too active in vitiligo. JAK inhibitors do, and that’s why it’s a good fit to use these medications for patients with vitiligo. It’s targeting the particular aspect that’s a problem for patients with vitiligo.
David Epstein, MD, MBA: I heard data from phase 2 that only 12% of the patients achieved.
David Rosmarin, MD: That was for ritlecitinib at the highest dose at 6 months. Twelve percent of patients achieved an F-VASI [Face Vitiligo Area Scoring Index] 75 in that study, with the caveat that it wasn’t designed exactly the same as the ruxolitinib cream study that Incyte ran.
Transcript edited for clarity.