Plaque Psoriasis: POETYK PSO-1 and POETYK PSO-2 Trials

Jerry Bagel, MD, MS, provides and overview of the phase 3 POETYK PSO-1 and POETYK PSO-2 trials, while Leon Kircik, MD, reviews the efficacy and safety of each of them.

Jerry Bagel, MD, MS:As far as the clinical trials in POETYK PSO-1 and PSO-2, it’s deucravacitinib 6 mg QD [every day], for 16 weeks, placebo-controlled double-blind studies. And what you find in the first study is that you end up with a PASI 75 [75% reduction in the Psoriasis Area and Severity Index] of about 60%. It’s close to what you see with Humira [adalimumab]; it’s close to what you see with Stelara [ustekinumab]. It’s a Stelara-like pill. When you compare it in a double-blind controlled study to apremilast, that drug comes through at a PASI 75 of 35%, and deucravacitinib at about 60% at week 16. But when you go out to week 24, deucravacitinib has a PASI 75 in the low 70% range. It keeps increasing over time, at 1 pill a day. And I’m excited about this. We saw good results in clinical trials. We didn’t see any significant adverse events, and I’m looking forward to a pill that I can hang my hat on.

Linda F Stein Gold, MD: That’s very true. To have another oral option that’s safe is going to be huge. Leon, talk to us about the safety, what did they see in the clinical trials?

Leon H. Kircik, MD:The safety data were clean. There were no systemic signals. They looked at all the laboratory tests and compared to apremilast and the placebo, and there wasn’t much difference. There is a great safety profile. The only thing that’s interesting, and it’s not explainable yet is that we saw some acne form and cysts, which is quite unusual. I don’t think we know why, but again, as I always say, we are in the business of dermatology, we know how to treat acne if a couple of people break out. I don’t think that was a big signal, but that was the only one that attracted attention. Jerry and Mark explained it so well, the allosteric inhibition and how it does not prevent binding the ATP [adenosine triphosphate] by competitive inhibition, but just changing the morphology of the molecule so that it gets crooked, and you cannot bind it there. The ATP cannot bind because the morphology changed, not because of competitive inhibition. What I would say is though the TYK2 [tyrosine kinase 2] is yelling and screaming to say that my name is not JAK [Janus kinase].

Linda F Stein Gold, MD: Yes. It’s more of the un-JAK inhibitor.

Jerry Bagel, MD, MS:There was a recent article that was accepted for publication that showed that there was no increase in malignancies in the TYK2 inhibition compared to the placebo group. That should help. Yes, I worry about where they’re going to be classified. I don’t see based upon the data, because you don’t see the lipids, you don’t see CPK [creatine phosphokinase], you don’t see anemias, the things that Mark alluded to. You don’t see that in the clinical trials with deucravacitinib. To me, it’s all about the data in regard to safety, and I don’t know why they would categorize it.

Linda F Stein Gold, MD: And that’s important, Jerry, because we do know that the FDA is conservative right now in terms of the JAK inhibitors as a class. We don’t know what the package insert will ultimately look like, but it is important to go back to the clinical data. And once this becomes available, we’ll hopefully have some long-term data that continue to support its safety. We can’t just lump JAK inhibitors together as just 1 big class, but we have to understand the nuances, especially with TYK2 inhibitors versus the other JAK inhibitors.

Thank you, Mark, Jerry, and Leon for this rich and informative discussion. Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

This transcript has been edited for clarity.