TRuE-AD1 and TRuE AD2: Trial Data

EP: 1.Overview of Atopic Dermatitis

EP: 2.TRuE-AD1 and TRuE AD2 Trial Overview

EP: 3.TRuE-AD1 and TRuE AD2 Trial: Baseline Characteristics

EP: 4.Ruxolitinib Trial Results

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EP: 5.TRuE-AD1 and TRuE AD2: Trial Data

EP: 6.Ruxolitinib: Clinical Context

EP: 7.TRuE-AD1 and TRuE-AD2 trials: Takeaway Points

EP: 8.Ruxolitinib Offers Rapid Pruritus Reduction

James Q. Del Rosso, DO: The mean itch change from baseline score was significantly decreased with ruxolitinib [Opzelura] cream compared to the vehicle at week 8. Now you’re looking at the nominal scores where they changed from the beginning. At week 8, the active group applying the 1.5% ruxolitinib cream went down 3.3 on that scale. The vehicle cream went down 1.5. So if you remember the mean at baseline was about 5.1. It was in the low 5s. You can see here how much difference there is between the active and the vehicle.

Now, let’s talk a little bit about the mechanism. This is a Janus kinase [JAK] inhibitor, and it inhibits Janus kinase 1 and Janus kinase 2. We recognize that inhibiting those enzymes has a lot of effects on the cytokines that relate to or that we believe are involved in the pathophysiology of atopic dermatitis. We know that ruxolitinib inhibits Janus kinase 1 and Janus kinase 2 predominantly, which has an effect on itching because Janus kinase 1 mediates interleukin 4, which stimulates itching on nerve endings. There are those JAK receptors or JAK enzymes on nerve endings, and that’s important. JAK 1 and JAK 2 affect other cytokines like interleukin 31 and TSLP, thymic stromal lymphopoietin. That’s a very important cytokine from keratinocytes early on and even later down the line stimulating both eczema and itching. One of the things you see here is you have the continued effect as long as you’re applying the ruxolitinib cream, it will show up early reducing the itching, but it stays the entire time. It doesn’t check out early. It doesn’t leave early because as long as you’re applying it, it will have the effect of inhibiting those Janus kinase enzymes, which reduces the effect of those cytokines on not only eczematous dermatitis but the itching. That’s a significant part of this.

When we look at patients who applied ruxolitinib cream vs. a vehicle, they demonstrated a shorter median time to achieving at least a 2-point reduction in itch. So now picture yourself being the individual patient or watching someone in your family or a friend that has this disease and they’re scratching, they’re really being bothered by it at baseline. By day 3, you’re now seeing them 3 days later, 42% that were applying the ruxolitinib cream had at least a 2-point reduction in itch. The vehicle cream only had a 15% reduction in itch. Then when you get to day 5, it continues to get better with more and more people. More and more people are capturing at least that 2-point reduction in itch, 53% with the ruxolitinib and 13.1% with the vehicle. So it kicks in pretty early in a lot of the people. They’re going to like that and then they’re going to be more likely to keep using it. If something starts working earlier, I’d be hard-pressed to have you show me a study where if everything else is good that patients are not going to adhere to it when it’s working. They’re going to be more likely to use it because it’s helping them.

Now, these are the patients that applied ruxolitinib cream vs. the vehicle which demonstrated a shorter median time to achieving itch. That’s a 2-point reduction in itch, which continued through the first week with a response noted as early as 12 hours. So now we’re looking at the clock and how this is affecting people over the week, but they don’t have to wait till the end of the week. These are people that within 12 hours, you’re showing at least a 2-point reduction in their baseline itch score. That’s about a little more than half of the patients applying the ruxolitinib 1.5% cream vs. maybe 2 out of 10 with the vehicle cream. The ruxolitinib cream kicked in early and over the course of that week, showed substantial improvement in itch.

This is looking at the proportion of patients achieving itch, which was at least a 2-point reduction in itch in the first week. You’re seeing here that graph what I talked about in the last graphic at 12 hours where it’s kicking in. The blue line is 1.5% ruxolitinib. This does show you the response in the lower concentration, which was not the one that was brought to market because you can see here the number is higher in 1.5%, but the 0.75% did very well also. So it shows you the activity of this drug in reducing itching vs. the vehicle, which is the gray line, which is obviously a lot lower. This is over the course of a week.

Now, this is a 4-point reduction in itching. So a 4-point reduction in that itch score was achieved by significantly more patients who applied ruxolitinib cream vs. the vehicle. You can see an impressive P value. This is by day 2. So within 2 days, how many got that 4-point reduction in an itch that high bar? You can see here it’s a little bit better than 1 out of 10 in the ruxolitinib cream and 2% in the vehicle cream. Substantially better kicking in with that higher amount of itch reduction, a 4-point reduction in itch by 2 days.

Significantly more people who use ruxolitinib cream had that 4-point reduction in itch within the first week. So now you’re marching along in both the ruxolitinib cream group and the vehicle group, and you’re seeing by day 3. Now you’re going to day 5. You’re seeing about 1 out of 4 had at least a 4-point reduction in an itch that applied ruxolitinib cream at day 5. Substantially lower in the vehicle cream. Then by day 7, you have about 30% with the ruxolitinib cream that had at least a 4-point reduction in itch. The vehicle cream hadn’t even gotten to 10% of the individuals yet so a substantial difference between ruxolitinib and the vehicle in its reduction. A 4-point reduction over a week.

Now, this is the proportion of patients achieving a 4-point reduction in itch within the first week. This is showing you the lines of how it progresses. You can see the lines continue to go up. So whatever it is they’re applying, as they continue to use it, more and more people are getting to that 4-point reduction in itch. But it’s best in the 1.5% ruxolitinib cream group. You can see the 0.75 was very good but lower. So it made sense to be going with the 1.5% ruxolitinib cream because you want something that’s going to work well. It’s going to reduce itching not only eczema, but the itching and going to do it quickly because these people are miserable. Anybody that takes care of them knows that.

The median time to treatment response. What does that mean? That means that half the people were longer than this and half the people were shorter. It’s that dividing line in the middle. The median time for 1.5% ruxolitinib cream to reach an itch reduction of 4 points was 13 days. The vehicle did not even get to a median time utilizing this metric. Next, improvements in itch 4-point reduction scores remain significant through week 8. You can see here a very impressive P value of .0001 and you have a little over half by week 8. The 1.5% ruxolitinib cream got a 4-point reduction in itch where the vehicle was shy of 20%. So this is that 4-point reduction. Remember there were subjects that got a 3-point reduction and a 2-point reduction, so it’s not as if everybody else didn’t have any effect. This was just a number that got that 4-point reduction.

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