Patrick Burnett, MD, PhD, FAAD, chief medical officer of Arcutis Biotherapeutics, speaks on the positive safety and efficacy profile shown in the DERMIS-1 and DERMIS-2 trials exploring use of roflumilast cream in patients with chronic plaque psoriasis, including those with intertriginous disease.
Roflumilast cream (ZoryveO) has shown significant efficacy and adequate safety in the treatment of patients with chronic plaque psoriasis, including those with intertriginous disease, said Patrick Burnett, MD, PhD, FAAD, chief medical officer of Arcutis Biotherapeutics.
Can you speak on the clinical safety and efficacy profile observed with roflumilast cream in the treatment of psoriasis?
The clinical profile that we've seen emerge for roflumilast cream in our 2 phase 3 studies, DERMIS-1 and DERMIS-2, each of these studies had about 440 subjects in them. And what we looked at was patients who had mild, moderate, or severe psoriasis—these patients were then treated for 8 weeks with regard to their topical psoriasis.
We randomized them about 2 to 1. So, we had more patients on the active cream than we did on the vehicle, and our primary end point that we looked at after 8 weeks of treatment is something called Investigator Global Assessment (IGA) success—this is the FDA preferred end point for studies looking at psoriasis. And the IGA scale is a 5-point scale going from 0, which is clear, all the way to 4, which is severe. And along the way, you have clear, almost clear, then mild, moderate, and severe.
As mentioned, we had mild, moderate, and severe patients enrolled in this trial and to be considered a responder on that primary end point, patients needed to get to a 0 or a 1, that means clear or almost clear, and have a 2-step improvement in their disease compared with baseline.
We also looked at a bunch of other end points. I think most importantly and unique to our development program was we did look at intertriginous disease. Early in our clinical development, we saw a very good safety profile and local tolerability, meaning we weren't seeing a lot of skin burning and irritation in patients. And so we thought this would be a very good fit for those intertriginous areas where topical therapies oftentimes don't work.
So, we looked at a very specific end point, intertriginous IGA (I-IGA) success, prospectively in those patients who had intertriginous disease, and we were able to show clinical benefit in them as well.
If I just kind of take a step back and look at the primary end point, which is IGA success, we reached that in 42% of patients in DERMIS-1, which is the first study, and about 38% of patients in DERMIS-2. So, about 40% of patients overall, at week 8, were at that IGA success end point. And this is a level of potency that is really, I think, very clinically meaningful to patients. So, getting a patient to clear or almost clear, which is one of the aspects that’s required, is really getting patients to the point where they have very little psoriasis on their skin in order to be considered a responder.
The other point that I think is worth talking about is our I-IGA success and here at 8 weeks, in those patients who had intertriginous disease, we actually got 70% in DERMIS-1 and about 68% in DERMIS-2 to this I-IGA success. So, very high response numbers in those patients who had intertriginous disease. And of those patients, the vast majority of them—60% overall achieved clear intertriginous skin at week 8.
So, of the patients who had intertriginous disease, most of them who responded were getting to completely clear on that end point. And I think that is something that really hasn't been seen with topical treatments previously, because it just hasn't really been studied effectively. So, that combined with our very good local safety profile, an adverse event profile that was observed with very low discontinuation numbers for patients in our 2 phase 3 trials, we think really puts a profile together that is going to support well the treatment of patients with chronic plaque psoriasis.