Plaque Psoriasis: Study Design of the VOYAGE Trials

NOVEMBER 25, 2019
HCPLive Network

Mark Lebwohl, MD: Let’s move on to guselkumab. These are the VOYAGE trials. The trial design differed substantially because the drug’s given week 0, week 4, and then every 2 months, every 8 weeks thereafter. That was 1 difference. But the other difference was the primary endpoint was picked at week 16. And in fact, even if you look at their data—and as we’ll see soon, the risankizumab data—they all actually peak later. Does anyone want to tell us about the VOYAGE data?

Brad Glick, DO, MPH: Well, one thing that I would say too is that I think it was really the first time we raised the bar in a clinical trial with PASI [Psoriasis Area and Severity Index] 90 being your primary endpoint, which I think really speaks to a lot of what’s happened in managing psoriasis patients these days in terms of bringing that clinical trial data then into clinical practice too.

Scott Gottlieb, MD: Right. I’ll talk about that in a second. On the VOYAGE 1 and VOYAGE 2 trials, the way I remember it is that the patients, as you said, were dosed at weeks 0, 4, and every 8 weeks thereafter. And the primary endpoint was at week 16. And again, this was the first drug that we used PASI 90 as a primary endpoint for. And somewhere between 70% and 73% of patients achieved that primary endpoint for PASI 90, which is crazy good, right? When we talk about these numbers, when you think about the patients and how well they’re responding to these drugs, it’s really overwhelming. But they did do well. The comparator was Humira, and they certainly did much better than Humira at all time points through the clinical trial out to a year.

Some other salient points about the trial that I think are important are that the group that was initially treated with Humira eventually crossed over at a year to receive Tremfya, and those patients did as they would have expected had they gotten Tremfya initially. But then there were also Humira failures who also crossed over to receive drug, and those patients also did much better on Tremfya than they did on Humira.

There are a couple of her studies. There’s the ECLIPSE study that was a head-to-head comparator between Cosentyx and Tremfya, and that met its primary endpoint, which was PASI 90 at week 48. So there are a number of clinical trials. There was the NAVIGATE trial, in which patients, if they failed Stelara, then were re-randomized either to continue Stelara or go to Tremfya, and the Tremfya arm did better.

I think that there’s a nice robust number of trials. I think the study designs gave us a lot of information. And then we also have to talk about safety because one of the themes of our panel has been that the class as a whole has really been a very safe class of drugs.

Brad Glick, DO, MPH: I think really all 3 drugs in the space are very similar. One thing I wanted to say that I like when I’m looking at clinical trial data too is that clearly the new generation drugs—when we talk about looking at guselkumab versus adalimumab—the believability of the trials is important too. Because when you look at the adalimumab arm, it looks very much like REVEAL trial data. The data at the end of the 16-week period are very much what we see in REVEAL.

Mark Lebwohl, MD: Which was the original adalimumab study.

Brad Glick, DO, MPH: Exactly.

Scott Gottlieb, MD: And the other thing to note is that both of the 2 trials, VOYAGE 1 and VOYAGE 2, did very similarly and when we get to risankizumab, those numbers were identical as well.

Mark Lebwohl, MD: Right.

Scott Gottlieb, MD: You always like to see nice correlation between 2 trials that had the same study design, and I think all the IL-23 [interleukin-23] inhibitors as a class show that.

Mark Lebwohl, MD: The tildrakizumab trials were also like that, you can practically put 1 on top of the other.

Scott Gottlieb, MD: Right.

George Han, MD, PhD: And I actually use one of those trials, the NAVIGATE trial that compared ustekinumab ineffective responders and switched them over to the guselkumab. I think that’s important because I think there’s an ideal where we’re targeting IL-12/23 already. Well should I switch a class? Would this patient do better on IL-17? And I think that gives us some confidence that, no, you don’t necessarily have to switch to a different mechanism. If you think about it, they’re all the same mechanism. So that gives you some confidence that a patient who perhaps wasn’t doing quite as well as they should have on ustekinumab can safely be put on an IL-23. And I actually think that makes more sense in my mind. They’re already used to that dosing regimen, the safety data are really good, and we can get additional efficacy out of putting them to 1 of these newer agents.

Scott Gottlieb, MD: And we could use that as a segue to risankizumab, which used ustekinumab as its comparator. So 2 different drugs with similar mechanisms of action. It was a gutsy study design. And of course, we know that risankizumab did better than ustekinumab in their clinical trial.

Transcript edited for clarity.

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