Oral TYK2 Inhibitor in Plaque Psoriasis

At the American Academy of Dermatology annual meeting, two parallel randomized trials showed that a majority of patients with plaque psoriasis had at least 75% improvement, and complete or near-complete clearance by physician assessment, after 16 weeks with the TYK2 inhibitor deucravacitinib.

MedPage Today brought together three expert leaders in the field: moderator Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, is joined by Joel Gelfand, MD, of the University of Pennsylvania in Philadelphia, and Neil Korman, MD, PhD, of Case Western Reserve University in Cleveland, for a virtual roundtable discussion. This third of four exclusive episodes focuses on the first-in-class oral TYK2 inhibitor deucravacitinib.

Following is a transcript of their remarks:

Blauvelt: Hello, everyone. My name is Dr. Andy Blauvelt. I'm a dermatologist from Portland, Oregon, at the Oregon Medical Research Center. I'm happy to be joined today by two of my friends and colleagues, Dr. Joel Gelfand from University of Pennsylvania, and Dr. Neil Korman from Case Western Reserve University.

So next I want to switch to another new drug that's slated to be FDA approved, or up for approval in the fall, in September of this year. It's a new type of drug, a TYK2 inhibitor called deucravacitinib.

We've seen some data on the phase III program in the last year. And I'm just curious to get your guys' take. I can cite the numbers -- we're seeing PASI [Psoriasis Area and Severity Index] 75 results in the high 50% range. Over the course of year it gets up into the high 60% range, and that's for PASI 75. It has, in a head-to-head, beat apremilast in the phase III studies. Not a big lift there, but certainly worth showing that data. And it's also an oral medication.

So here we have a potential new oral medication, modest efficacy, that blocks TYK2. So Neil, what are your thoughts on this new possible drug?

Korman: I like this drug. I think that a lot of our patients are: "Aaah, a shot -- I still don't want a shot!" I mean, I think that we've had our hands tied by the kind of very old school orals that we've had that have been pretty toxic or ineffective, or both. So I think deucravacitinib with those kinds of numbers, they certainly doesn't compete head-to-head with just efficacy with our best 17 or 23 inhibitors. But the safety profile looks pretty clean.

So this TYK2 is a part of the JAK [Janus kinase] family of molecules, but it's different. And the side effect profile does not show any of the mess that the JAK inhibitors seem to show with increased risk of an infection, zoster, and malignancy, and cardiovascular disease -- the whole long list of things that at least in theory we have to deal with and think about. Even though I don't think they're super common in the JAK inhibitors.

But I think this is a different class. We'll see if the FDA buys that or not, but I'm very excited about it. It's one of the first potential new orals that we've had in a long time. And we'll also be studying it in psoriatic arthritis as well.

Blauvelt: Joel, what do you think of deucravacitinib and what the FDA might say?

Gelfand: Well, I think the clinical data are very impressive so far -- the efficacy that you've mentioned. But there also doesn't seem to be any evidence of laboratory abnormalities that you may see with JAK inhibitors. And there wasn't much of a zoster signal at all, or malignancy signal. And so that's really encouraging. It doesn't seem to behave like a JAK on those safety endpoints.

The main thing we have to think about as clinicians is, it is a new molecular entity. It's really a new first in class kind of drug. And so usually you'll need several thousands of patients treated for a couple years to get a better insight into what the long-term safety issues may be.

We'll know, at this point, that the drug's unlikely to be associated with any serious common side effects. But things are uncommon. One in 100 or 1 in 1,000 certainly may pop up as you learn more about it.

I think this drug is addressing a major unmet medical need. An oral medication once a day, very well tolerated, with no nuisance side effects, like GI intolerance that you'll see with apremilast. And respectable efficacy.

And as Neil mentioned, for many patients despite the tolerability and efficacy of biologics, the injectable nature of them is a bridge they don't want to cross. I think this will be a very popular medication with a lot of our patients.

Blauvelt: Yeah, and I just wanted to add that, yes, TYK2 is a member of the JAK family, but it's involved in signaling of mostly inflammatory processes and not sort of normal biologic processes. And it's very selective for TYK2. So we don't see any blocking of JAK 1, 2, or 3. And so for me, it is very clear that it's kind of a new type of drug, selective TYK2 blocker, that we have to view in that manner.

Watch episode one of this discussion: Cardiovascular Risk in Patients With Psoriasis

Watch episode two of this discussion: Bimekizumab Shows Promise in Moderate to Severe Plaque Psoriasis

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