← Derms on Drugs
Loading summary
Transcript205 lines
- [00:04]
A
Welcome to another special episode of Derms on Drugs, a video podcast brought to you by Scholars of Medicine. The best educational platform and dermatology and provided at no cost to medical providers. Derms on Drugs is for cutting edge dermies, hit or miss comedy. I'm Dr. Matt Sierra from Docs Dermatology, and each week I'm joined by residency buddies, Dr. Laura Faris from the University of North Carolina, Dr. Tim Patton from the University of Pittsburgh, and we use our 60 years of combined derma experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be in the cutting edge of derm and it actually have some fun listening. New episodes drop every Friday on Scholarship Medicine, Apple Podcast, Spotify and other major podcast platforms. And I highly recommend you download the Scholarship Medicine app to access the full podcast video archive and explore what is quite literally the best derm educational content out there. We're talking real, active, actual education, not pharma pushed crap, right? Coverage of all dermatology, core curriculum, what's hot, what's new, all kinds of good stuff. And it's supported by an amazing AI clinical consultant called Ask Simon. So this week we've got, as I said, another special episode back into the aad, Late Breaking Abstracts and let's get right to it. Actually, before we get right to it, I do want to say last week I finished on Vel bellumab for pytorm gangrenosum. And then I did want to say that was presented by Dr. Ben Kaffenberger from the Ohio State University. The Ohio State University, who years and years ago was one of my residents. I would like to say that I trained him, but mostly it was just that when he was a medical student, I was like, man, this guy's going to be the best doctor I've ever met in my entire life. And I was able to recruit him into Durham and then stay out of his out way while he became a much better dermatologist than me. So now we're ready to get into it. Dr. Farris, what do you got?
- [01:54]
B
All right, so my first presentation was ixakizumab plus tirzepatide for patients with psoriatic arthritis. This is together PSA A Phase 3B randomized trial 15.
- [02:08]
A
Wait, wait, wait, wait. Why? Why PSA? Why did they do this in psoriasis?
- [02:11]
B
They are doing it in psoriasis as well.
- [02:14]
A
Okay, okay, okay.
- [02:15]
B
But this is the first one, and this one actually was published like the day that the embargo lifted. So you can actually find the whole paper. Okay, so what did they look at? They com. They looked at efficacy and safety of ixacizumab plus tirzepatide. So TALTS plus a GLP1 and compared to ixekizumab alone in adults with active PSA who were also either overweight with at least one comorbidity or obese, meaning BMI over 30. Primary outcome, which is a little funny, like, yeah, of course you're going to win. This one was at week 36, the achievement of both ACR 50 and greater than 10% weight reduction. Okay, so like one group I starved and then the other one I did not. Which one lost more weight? So, okay, so 31.7% of participants achieved that outcome versus points eight achieved the. You know, with ixakizumab alone. So you don't lose weight on ixakizumab. You do on tirzepatide.
- [03:19]
A
Now that is the best, you know, how they like to present the ratio of like or the treatment was five times more likely. It was 8,000 times more likely.
- [03:32]
B
Right. To achieve. Okay, but I will say this, that there was. They did just look at what percentage of patients achieved ACR 50 and. And for the combination it was 33.5% versus for ixakizumab alone it was 20%. So that is kind of a significant difference.
- [03:54]
A
Wait, like twice as many got it on the combo?
- [03:57]
B
Yeah. So definitely CR50. That's not just weight loss. So I thought that that.
- [04:03]
A
Did they say, was there a direct correlation between how much weight you lost and how much better your. Your. Your psoriatic arthritis got? Or were they.
- [04:13]
B
If they did, they did I. That from it. Yeah, it may be like dug in the paper somewhere.
- [04:19]
A
Okay.
- [04:20]
B
So, you know, and if. And it kind of like it achieved. So yeah, it was really like. They also looked at like, what about ACR 20 plus 5% of weight reduction and that was like 10% talts alone, 69.7% of the two drugs together. So, yes, it does look like it impacts that. Now, interestingly, looking for a little bit of psoriasis data in the paper. So, you know, realize this is a PSA paper, so not everybody's got psoriasis. And but they did measure it in the people who did have cutaneous involvement, and they actually did show that the reduction in PASI score was greater in the group that got both drugs. So a reduction of 4.3 versus 3.3 for the patients who got talts but not tirzepatide. And again, these Were not people starting with a PASI of 12 or 20. You know, they may have had a PASI score of like 4. So. Or 5. So I think it's going to be really interesting when we see the dedicated study.
- [05:22]
A
Agree. This is, this could be a bombshell for Lily. If it's like if that. If the psoriasis data shows that it works twice as well with. I mean. Well, it's not. You couldn't. Right. It's already getting like. It was twice as well. People. 130% of people would, would get to, you know, passy 90. So that seems, seems unlikely. But if anybody can do it, it's Lily.
- [05:45]
B
That's right.
- [05:45]
A
Anybody can do it, it's Lily.
- [05:47]
B
Yeah. So interesting, I thought, I mean, the ACR 50 alone being that different. 20% versus 33.5. That was, I thought, kind of provocative.
- [05:59]
A
Yes. All right, here we go. Hold on. I had AI look it up. The short answer. The data suggest the PSA improvement is at least partially independent of weight loss. Merola noted that ACR 50 began to improve as early as week four, before there was any meaningful weight change between the groups, which he flagged as a sign that maybe there's impact beyond the weight loss. Okay.
- [06:21]
B
All right.
- [06:22]
A
Interesting. All right, Patton, what do you got?
- [06:25]
C
Povor sitinib in hydride 90 supper sitting up is a jack one inhibitor. Probably more so than either UPA or ABBA or. Not probably. I mean, it is. Right.
- [06:38]
A
Abro is also super Jack one specific. They're probably, probably.
- [06:41]
C
I think this is even, even more so.
- [06:44]
A
Abro is 10,000 times more Jack 1 than Jack 2.
- [06:48]
C
This is 30 million. All right, let's go on this abstract reported the data from two phase three HS trials. Stop HS1 and stop HS2. That's a great name for a trial. That's the best HS trial name ever. This was a big phase three HS study. Moderate to severe H. Povor 35 versus Povor 75 versus placebo.
- [07:14]
A
They call it Povo. Povo is. Is how the company refers to it.
- [07:18]
C
I don't care. I don't work for them. I call Povor. And then they. So they did 45 versus 75 milligrams versus 12 or I'm sorry, versus placebo for 12 weeks and then a 42 week extension of the 45 versus the 75. Both doses met the primary endpoint at week 12. They didn't give specific numbers in the abstract. Long term 54 week data is reported as pooled data between the two groups. So high score 50, 58 to 66% of patients reached it. High score 75, 41 to 54% of patients reached it. And like a high score 100, which I don't think any biology, any HS treatment has given us. High score 100 numbers. 20 to 27% of Povo people had that. Those are all pretty good, I think. Decreases in inflammatory lesions, draining tunnel skin pain, fatigue, dlqi. That was all reported statistically significantly better. In the POGO group, there were three embolic events, one MACE event, one death. They actually went over the death. Not a terribly healthy person, it sounded like. So yeah, I mean, I think POVO looks pretty good, right? I mean those, those numbers are pretty good. And it's, it was phase three data. It's not like a phase two or whatever is that.
- [08:42]
B
Didn't we have, didn't we have, high score 100 responses for Bimakizumab when we did the paper a few episodes ago. I think there's like a low rate, but it was in like long term extension and things like that. So. But yeah, so it be interesting if this is an oral medication that has the efficacy of bimakizumab.
- [09:01]
C
Yeah, I want to say it was like 10 to 15% for Bimmy.
- [09:05]
B
Yeah, yeah. Interesting.
- [09:10]
A
It is, it's going to be, it's, it's going to be cool to have lots of at least multiple drugs that work for hs. It's going to be cool.
- [09:22]
B
Yeah. And I think what'll be interesting is seeing if you can like reduce the formation of tunnels and scarring and all that stuff.
- [09:28]
A
So window of opportunity.
- [09:31]
B
Window of opportunity. It's all about the window, my friends.
- [09:34]
A
All about the window. That's right. Got to keep the window open.
- [09:38]
B
That's right.
- [09:38]
A
All right.
- [09:39]
C
Yes. So with the window of opportunity, they were like, okay, if they have a high score of 4, that's moderate to severe disease. So you'll get, you'll get them down to one nodule and that'll be your 75%. That'll be high score 75%.
- [09:55]
A
Right on. Yeah, that's right on. Right.
- [09:58]
B
Although they will not get into a trial with that.
- [10:00]
A
Just FYI, they. Right, they need five to get into a trial. All right, so my first one for this part blew me the heck away. So this was, and I forgot to take a picture of the title slide, but this was a laser for hair androgenic alopecia or pattern alopecia, whatever the heck you want to call it was like a 1562 or a 1565 laser. Or something like that. And 1565 laser, I don't think it's commercially available on the market yet, but basically it is powered to, like, heat the hair follicle up enough to be stimulatory, but not enough to, like, kill anything. And son of a gun, the data was pretty impressive. And they showed before and after pictures, and it was pretty impressive. And this was monotherapy, so these people were not getting, you know, oral minoxidil, finasteride, spironolactone, topicals, prp, like, any of it. This was exciting. So this is one of the first things that I could imagine being a procedure for hair loss that is feasible for normal patients. Right. Because I always think, like, I mean, it depend on the pricing more than anything else, but I always. I always feel like PRP is too pricey. Hair transplants are too pricey. Like, the majority of my patients are not going to do any of that. But, you know, if it's 400 bucks to get this laser and you get six treatments in a year or something like that, I could see patient, and then, you know, you need one or two a year to maintain. I could see patients doing that. So this was. This was pretty cool. This is new and new and important. So, yeah, that's it. I'm still a fan of the red light therapy. The, you know, the. The red light helmets. They still sound ridiculous, but I do think they work. So, yeah, that's it. You guys got anything interesting to say?
- [12:11]
B
No, I saw the pictures look good. I mean, it's interesting.
- [12:14]
C
It's interesting.
- [12:17]
B
I understand. I mean, I. I heard the explanation of, like, it warms the hair follicle, like, just enough, but. Yeah. Feels like that's not usually how lasers work, but it is interesting.
- [12:28]
A
Patton, did you schedule your first appointment yet?
- [12:32]
C
I'm very happy with my receding hairline, thank you very much. You could.
- [12:36]
A
You could probably get a discount if you're like, hey, I'm on this podcast.
- [12:40]
C
I'll talk about it.
- [12:41]
A
And if I come and give you. If I show up with, you know, Fabio, like, hair.
- [12:48]
B
That's right.
- [12:49]
C
I can get Fabio hair. I just choose to keep it short like this. What I want is, like, down on the forehead. So that fair. Like, I just. I want this less of a forehead.
- [13:02]
A
Three quarters of your forehead gone. Okay.
- [13:06]
C
Yeah, they get a 3.2 head.
- [13:12]
A
I can't believe I've never heard that before.
- [13:14]
B
God. Anyway, moving on to them.
- [13:17]
A
All right, what do you got, Ferris? What's next?
- [13:20]
B
So this next one is Zaza, sit nib for psoriasis. So two randomized multicenter double blind placebo active comparative controlled phase three studies, latitude three and three. So each, you know, these were pretty big studies. 693 and 1 and 1108 and two. So this was Zasoc, known as a next, another next generation tick 2 inhibitor. AI optimized to have a very high affinity for tick 2 and high levels of inhibition compared to placebo and our old friend apremolast CO primary endpoints PGA01 or PASI75 at week 16. So what did we see at week 16? About 70% of patients on Zazzo reached a PGA0 or 1 and in a Premolas that was around 30% similar. Pazi75 it was about, you know, low 70s percents for Zazo and it was 12% for placebo and a Premolast around 37 and 33%. They did a Pazi100 numbers and those were 33% and 25%. In the Zaza sitib group reached Aazi100 versus placebo, it was 0.7 and 1.1 and in a Premast it was 2.9 and 4.3%. At week 16, AES that they saw were uris, nasopharyngitis, kind of a high amount and then acne as well. If we look at they had some week 24 data, Pazi 100 was like 42% and for Zaza sitinib 32% for premolastin. Right. No. Am I reading that right? Pazi 100 at week 24 was. Yeah. Zaza civnib 42% of premolast 5%. So now you're going to ask me which one's better in voodoo? I don't know. I still don't know. I don't have the answer. I mean it's still like not huge study size or. It's not huge. I mean the, the Zazzo study is definitely a bigger study. And I don't know yet what I think. I mean the numbers versus the Premalast, I mean they're kind of similar. Right. There's not enough for me to say it's 100% this. Do you have a feeling?
- [16:16]
A
Well, no, I do not. I like Takeda. They're. They're kind of their cool company. They're super old company from Japan. More my thing that I want to discuss.
- [16:29]
C
I.
- [16:30]
A
So this is going to be a controversial take, unlike most of what my takes are.
- [16:33]
B
Yeah.
- [16:34]
A
So I think that icotide is going to be a disappointment. I think that the take on an empty stomach is going to make it and the pharmacokinetics of it, I think are going to make it so that if people are not 100% compliant like perfectly, that I think we're going to not See the Phase 3 results replicate or, I'm sorry, the real life use replicate face to face three results. Now this is, this is a Steve Feldman question.
- [17:07]
B
Yeah, withdrawal rate, like if you look at the loss of response when you stop iotide, it's not like it drops off like this. It's pretty gradual. So, you know, there is still some aisle 23 effect. One, two, not taking it on an empty stomach, you know, it will decrease absorption a little bit if you take it with caloric foods. So like you could take it with a little black coffee and you'd be fine. And it's 30 minutes. Right. So is that the end of the world? I mean, like, do you really get up and like stuff? Like I definitely get up and have coffee within 30 minutes, but I don't know that I get up and have like a meal within 30 minutes. So maybe you reduce absorption by 20%. It's not like you blow up or something. Like you don't explode if you have food. So it's not like, you know what I mean? Like, I don't.
- [17:58]
C
That would be.
- [17:58]
A
Are you, did they. Was that an adverse event of special interest?
- [18:01]
B
It was, yeah.
- [18:03]
A
They showed no explosions.
- [18:05]
B
So here's what I would say. What do we always say a premolast is? Otesla does so. Well, because you don't have to check any labs, right. Icotide is now approved. You don't have to check any labs. So if you have a better drug where you don't have to check any labs, I still think it's going to be. People use a ton of a premolast for not checking labs and it does not work very well.
- [18:29]
A
That'd be the one. If I was, if I was in a clinical trial for otesla, I would be hoping to get placebo so that I didn't have to worry about the nausea and the, in the diarrhea. You got basically equal odds of getting nausea and diarrhea as you do of having it work. It's just crazy. Crazy. All right, moving along. Patton, what do you got?
- [18:53]
C
Sonalikumab. So sonalikumab is a nanobody. It's like I, it's like Bimzel X, It's I, anti IL, 17A and F. But it's like, it's like loosey goosey. Like bimzelics is rigid and stiff, and it can't, like, make tight corners. And sonalikumab is smaller, and it's like flexible.
- [19:18]
A
So it's like you and me. You're. It's kind of like the bimselics is a patent in the sonolikumab is a zyrus.
- [19:27]
C
I don't know. I think I'm pretty loosey goosey, but fine.
- [19:31]
A
Isn't it also smaller? Is it not smaller also?
- [19:35]
C
Yeah, so it is. So it is like you. Yeah, it is. It is smaller. Yes, it is. So not smaller. Like, I want to say the flexibility. I don't know. I just like the idea of like this wavy, flexible. But you're right, it's also smaller. So the. The linking thing is something that binds to albumin, and that's a big part of it. So with a small molecule, what you'd worry about is it would get filtered out of the kidneys pretty quickly. But by binding it. But because it kind of piggybacks along albumin because of that center portion of the nanobody, it doesn't get filtered out by the kidneys. And albumin tends to also get to sites of inflammation. That's just a thing albumin does, I guess.
- [20:21]
A
But doesn't the albumin keep it from getting out of the blood vessels? Doesn't it need to get out of the blood vessels and into the tissue?
- [20:27]
C
Not apparently. Like, not when there's inflammation. Which is why, like, you think of serum and plasma, like, that kind of leeches out when you. Yeah. So kind of neat technology.
- [20:37]
A
Okay, is it? Didn't you say this comes from a weird thing like a.
- [20:42]
B
A camel?
- [20:44]
A
Oh, I was thinking. I was. For some reason in my head, it was an octopus.
- [20:48]
C
Okay.
- [20:49]
A
It's a camel.
- [20:49]
B
I don't think that's because of my make antibodies. I'm just gonna go on record of saying that I could be wrong. But what.
- [20:56]
A
How could.
- [20:56]
C
You couldn't live without an antibodies. All right, so sonalikumab in HS dosed every two weeks up to week six, and then every four weeks. And then the placebo group crossed over at week 16. This is data from week 40. This was the Vela 1 and Vella 2 trials. So, I mean, so just, you know, going through the numbers. 50 reached by 75% high score, 75 reached by 60% high score, 90 by 35% high score, 100 by 25%. So on the higher end, high score, 100. That's pretty comparable to what they saw with the POVO study. But the high score 50 numbers. The high score 75 numbers. I mean, little bit better than what the POVO data showed. So just to go back, the high score 50 on the povo was 58 to 66. And for sonolicumab, 75.
- [21:48]
B
Whoa.
- [21:49]
C
And I. What? I'm sorry, go ahead.
- [21:51]
B
Oh, that's just impressive. Yeah. Whoa.
- [21:53]
C
Yeah. No, and. And it, I mean, it technically was a little bit shorter too. Right. It was 40 weeks in the sonalicumab, and they looked at it at 54 in the povo, but just like really impressive numbers. And again, this is. These are phase three trials. This isn't the early stuff. And. Yes. So I think sonolicumab. That one looks pretty excited. Rates of oral candidiasis weren't reported in the abstract, but AI looked it up for me. And if I believe AI, which I do because I'm too lazy to verify anything, it tells me 7.3% saw oral candidiasis compared to 0.4 on the placebo.
- [22:32]
B
But that's better than BIM is, than bimakizumab. Right. I think with bimmy. Right. It's oral candidiasis or candidiasis of any area. So I. I don't know. I. I thought that that was pretty interesting. And I remember when we looked at. We reviewed a network meta analysis and Sonalocumab was also in there, and they basically said, like, it looks like it's the most effective one, but it's not really powered like that. The P value wasn't significant, like, as it was smaller studies. Now that we've got phase three data, if somebody reruns the nma, it'd be interesting to see if it comes out.
- [23:16]
A
Yeah.
- [23:16]
C
I remember sonolikumab being at the top of that nma and I had not even heard of sonolikumab at that point when we reviewed that earlier.
- [23:23]
B
So I think I'm gonna call it Sona Locumab just to stake our claims on pronunciation of everything.
- [23:30]
C
Sonil Locamab. Yeah, that's what it looks like.
- [23:34]
B
Okay.
- [23:37]
A
To me, it's not. It's no longer a nano body, It's a camo body.
- [23:40]
B
That's a camo body. All right. They're probably not going to hire us for marketing for this.
- [23:46]
A
This.
- [23:47]
C
This is early draft stuff. This is brainstorming. This is whiteboard stuff. We'll refine this and they will be coming to us asking what's the best plan?
- [23:57]
A
So next one. I don't think I told you Guys, I was going to do this one because I forgot it was out there. Dupilumab reduces keloid dimensions and halts fibrosis. So first, I'll tell you the part that I think is exciting. So, weekly DUPY versus placebo for 24 weeks, followed by crossover. And so people got up to 52 weeks of dupy, and it was statistically significantly better than placebo from week eight on. But the total percent reduction in the height of the keloids, 12.9%. So not like, ooh, it makes your keloids melt away. And so I don't think this is going to become a monotherapy for keloids. But what I could see is, you go on doopie, get your keloids excised, injected, like whatever else we would do to a keloid, and we might see that combo therapy makes a lot of sense. Like, this is the other. The other drug. Just if. No, people haven't seen this before, there's some data out there for pentoxifylane as sort of combo therapy to help prevent recurrence, which is cheap and easy.
- [25:15]
C
AI it.
- [25:16]
A
And you'll find everything you need to know about it. But that's an interesting cheap and easy one. But doopie, right? People have been talking about doopie for keloids for a long time, and this was the first to me, quality data that says, yes, it definitely does something. Doesn't do enough on its own, but it definitely does something that might be good as combo therapy. That was. That was kind of my takeaway of it. All right.
- [25:37]
B
Okay. And it is. They gave it systemically. They didn't do it intralesionally, right?
- [25:43]
A
Correct. They gave it systemically. Yes. That is my. I'm 99% certain of that.
- [25:52]
C
It was. Yeah. I mean, it's. That's way impractical. I mean, I. The pictures were impressive as monotherapy, it's like, yeah, it seems to treat keloids. I. I couldn't imagine the keloids spontaneously getting the response in the pictures.
- [26:07]
A
Practical, though, what that. What's impractical about a weekly injection once a week?
- [26:12]
C
It's. It's $400,000 a year.
- [26:16]
B
No.
- [26:16]
C
What would it be? It'd be a hundred and it'd be $120,000 a year to get a response that you could get with intral Tack. Like, when I saw the pictures, I'm like, il Tack would do the same thing.
- [26:29]
A
Okay, fair.
- [26:31]
C
I. It's like, I. I never thought of keloids as a. As a th2 like thing. So that was interesting.
- [26:39]
A
I don't think it is a TH2 thing. I think fibroblasts have the io13 receptor on them. I think io13 directly activates keloids. It activates fibroblasts. So it's not. Now, maybe that's part of the th of th2ness or whatever, but I don't think it's a general inflammatory thing. I think it's just IL13 receptors literally on fibroblasts. All right, let's move along. Ferris, what do you got?
- [27:04]
B
All right, I'm gonna double up, which means you can skip me on the next round. So this is. These were two abstracts basically by the same company, looking at the performance of something called Derm Plus. What is that? It's an iPhone program. Basically, it's an iPhone with a dermatoscope on it. And you get the dramatoscopic image and it classifies lesions as benign or malignant. There is this device called Derm, which is used in the uk and they state that this is actually. It has more advanced. That one has more advanced AI than Derm Plus. So this was a, like a. These were like US and Italy based studies. So the first study was like, how precise is it? Meaning how re. How repeatable and reproducible is this for AI detection? So what they did was they used Derm plus to assess lesions that were already scheduled for biopsy. So everything got biopsied. It's a prospective cross sectional multicenter study. This one was actually done in the uk sorry. The next one was done in the US and Italy. So each lesion was basically multiplied, was imaged multiple times by three different operators using three different smartphones. And the images were assessed by Derm Plus. And their aim was to show, you know, and so there's a little bit of like, how accurate is this too? Not just how reproducible is it? So they're, you know, the endpoint that they were trying to reach was to. Was to demonstrate the average positive agreement for repeatability and reproducibility possibility of greater than 80% for malignant lesions and the average negative agreement for. Of greater than 50% for benign lesions. So 115 patients recruited. They 6. They had 61 malignant lesions. And those were, you know, mostly basil and squams. But there were 11 melanomas. There's only one Sep K here. I thought that was interesting. So the. So the APA was 100%, so detected all the cancers and it was re. Repeatable and reproducible. And then the. The negative, the average negative. The ANA was 80.8%, which was. And, no, sorry, the. The repeatability ANA was 80%. The reproducible ANA was 64%. So it didn't, it wasn't quite as much agreement there, but it was achieved a sensitivity to malignant lesions of 100%. The specificity was 18%.
- [29:48]
A
So wait, wait, wait, wait, wait.
- [29:49]
B
Do you want me to re. Explain APA and ana?
- [29:55]
A
Yes, but I also just want to make sure I understand specificity. So that means it was wrong. It called things malignant, things that were benign. It called the malignant 80% of the time.
- [30:08]
B
Yes. This is the problem with most of the devices out there. So it will pick up the malignant things. The problem is it doesn't. So it's high sensitivity. It doesn't have a lot of specificity.
- [30:18]
A
Okay, and what's APA and a what?
- [30:20]
B
Absolute positive, average positive agreement and average negative agreement. Like, how much do we all agree? Yes, this is a cancer. Or how much do we all agree? No, this is not a cancer.
- [30:33]
A
Okay.
- [30:33]
B
Yeah.
- [30:34]
A
Okay. That's okay.
- [30:35]
B
Okay. Okay. So that was like re. So. So sensitivity, 100%. Specificity, 18%. Second study, clinical validation study. This is done in 16 dermatology clinics across the U.S. and Italy. And so they're sort of threshold, and there's a word for this that's escaping me, but looking for. They wanted to see a sensitivity for melanoma of greater than 90% and a specificity for all malignancy of greater than 20%. This was over a thousand. Over 1100 patients, over 1200 lesions. 513 of those were cancer, 126 were melanomas. SEBK number here was interestingly, 77. Okay, so they looked at sensitivity. How often did it accurate, accurately. If something was a cancer, did it call it cancer? For melanoma it was 93.7% and for squamous cell it was a hundred percent, for basal cell was 99. And the specificity here for non malignant lesions was 24.4%. So they did use a, a panel for a dermatopathologist for the pigmented lesion. So, you know, dermatologic dermpath A's melanoma is not always dermpath B's melanoma. Little more agreement for things like basal cell. And so, you know, their goal is to try to market this in the US for, you know, evaluating pigmented lesions. The way they use this in the UK is in, you know, in this slightly different version is you go to a gp, you got A skin lesion, they put it through. If it says, nope, that's benign. They do not refer you to dermatology. If it's positive, then you get referred to dermatology. So I don't know. I don't know what their goal is. If it's like they, they want dermatologists in the US to use this. There's a little bit less regulatory hurdle if you have a tool that's a decision support tool for a dermatologist, you know, than if it's like a standalone diagnostic device.
- [32:40]
A
So if I, if I'm a dermatologist, I'm getting this immediately. 80% of the time, it tells you to biopsy. Think of all the money we can make.
- [32:49]
B
Big study in the U.S. dermatologist, selected lesions. The specificity was higher as 24.4%.
- [32:55]
A
So 24 in that case. Well, fine.
- [32:57]
B
So it's going to tell you to biopsy 75% of the time. So you use these original studies on melafine. The specificity was 10%. So it told you to biopsy 90% of the time.
- [33:08]
A
Well, I remember we were in that hotel room drinking. Not just the three of us, it was a whole group of people. And we told Pat he had a melanoma.
- [33:17]
B
I don't think I told him he had melanoma. I think the device said suspicious lesion,
- [33:23]
C
but said, cut it.
- [33:24]
B
Still alive.
- [33:25]
A
So did you get it removed? Did you get it removed?
- [33:28]
C
Yeah, man.
- [33:30]
B
Yes, I know.
- [33:33]
C
It was benign, by the way. Matt didn't even care what it was.
- [33:37]
B
Yeah, Just.
- [33:38]
C
It was benign.
- [33:39]
B
You're going to be a wolf no matter what. But yeah, so, yeah, this is going to be the challenge.
- [33:46]
C
Thanks for your. Thanks for your concern.
- [33:49]
A
So you're trying to tell me your hair loss is from chemo? That's what I was. It would have made sense.
- [33:55]
B
Yeah. I mean, so the problem is going to be how do you use this if you're like, let me put this on everything that the patient is worried about. You're going to do a ton more biopsies. If you say everything I'm planning to biopsy, I'll use this on. Maybe it will reduce your biopsies by 25%.
- [34:12]
A
No, we got to use it on everything. We don't think we're going to biopsy.
- [34:16]
B
If that's. If your goal is to do a lot of biopsies, that is the intended use, then yes, but probably not the best way to do it.
- [34:23]
A
All right, so now what about the Amer? Wait, did you already cover the American Study.
- [34:28]
B
Yeah, that was that. The second one was UK. I'm sorry, was US, Italy, the one that had the 1100 plus patients in it.
- [34:37]
A
So how close fares? I know you're like world expert on all of this. What's the one that's coming that is like the full body polarized dermoscopy, is that making its way towards utilization?
- [34:56]
B
I think it's not commercially available yet. So basically the robot that can go around, look at all the moles and do such high, high, you know, resolution, close up imaging that you get what looks like dermoscopy. I think that will be interesting. I don't know where it is in terms of being available. I know that it is being worked on to be a commercial product. I mean, to me, then you can have AI that can, you know, pick out the most atypical lesion it can you can do. To me, these are going to be helpful as serial images, right? It's not just what it looks like now. If it's not changing, it's not a bad cancer. We could leave it. So if we only look for things that change, we might be able to actually find biologically relevant tumors. That's my hope for our future.
- [35:41]
A
Yeah, change. That's change. Right on.
- [35:44]
B
Change where it's at. Yeah.
- [35:46]
A
Yep. All right, Patton, what do you got next?
- [35:50]
C
LP003 for CSU. This was presented by.
- [35:59]
A
You don't care who presented it. Just tell us what happened.
- [36:02]
C
I know, but they got up there and spoke and I think they want to be acknowledged. I'm still going, right?
- [36:07]
B
Unless Matt. Unless they happen to be Matt's resident. Then it's important.
- [36:10]
C
Yeah, right. I mean, you really singled out your residence. We were supposed to be an unbiased dermatologist, like someone that listeners can trust. And you're blowing it, blowing it, blowing it.
- [36:25]
A
All right.
- [36:25]
C
LP003 is an anti IgE antibody with enhanced affinity, enhanced FC epsilon R1 inhibition and longer half life compared to OMA. So this was data from a phase two trial. Three doses of LP003 compared to placebo and the 300 monthly dose of UMA. So there's lots of numbers I like. I always like the proportion of patients reaching UAS 7 at zero. Right. That's what you. You want the patient to come back and be like, I don't have hives anymore. So those numbers, 44.4% for the 100 milligram every eight weeks of this new drug, 66.7. If for the 200 milligrams every eight weeks, 57.5 for the 200 milligrams every four weeks. That was a little bit odd that the, the 200 milligram every four did not do as well as the 200 milligram every eight. Little bit odd. How did OMA compare? 43.6. So it was better than omalizumab. Placebo was 50% better.
- [37:28]
A
Yeah, 50% better.
- [37:29]
B
That's pretty big, right?
- [37:32]
A
Yep.
- [37:34]
C
Yeah. So similar sorts of numbers for the least squares mean change from baseline, blah blah, blah. Week four data seem to indicate that this superior response happened pretty quickly. So there's a new shiny anti IG antibody. Kind of interesting. This is like deja vu, right? There was a phase 2 trial, legolizumab bound to higher affinity anti IgE. Phase 2 data looked really, really good. And when they came out with the phase 3 larger study, it was really no better than omalizumab. And whoever made legolizumab, I forget who it was, they, they stopped pursuing that indication based on the phase three data. So we'll see what happens. But preliminary stuff looked pretty good.
- [38:17]
A
Okay, fair. That's good stuff. Okay, so let's see my next one. Efficacy and safety of abrasitinib in patients with chronic hand eczema. Ray noise double blind multicenter placebo controlled trial. And I will give you the takeaway. It works really, really, really, really, really, really good or well. Yeah, 80, 80% ish of people do like 80, 90% of people do phenomenally well. So basically I would say it's just as good in hand eczema as it is in atopic dermatitis. And that's, that's interesting because hand eczema is primarily irritant dermatitis. And then there's some contact derm in there and there's some atopic derm in there. But so this is, this is it. It is interesting because the way that you, that we should think about hand eczema, you need broad spectrum anti inflammatory that does not impair the skin barrier. Because that's the problem with steroids is you take steroids for three days, you use a topical steroid for three days, your skin barrier is dramatically impaired. And so it helps bring down the non specific inflammation from the irritation, but then it's making the barrier worse. You use a JAK inhibitor topically or orally and you can break down the inflammation without destroying your barrier. And so it's just, it's interesting what you would have predicted. But still interesting though that's, that's where we Are. And it's. So I think the numbers are certainly better than for an topical jack, which was interesting. I would have predicted that oral topical jacks would have worked better, but it does look like. My guess is the orals are more effective. So where we are.
- [40:11]
C
My summary. Yeah, My summary of this is chronic hand eczema is atopic derm. Abra works for atopic derm. Abra works for ch.
- [40:21]
A
That's. That's. So that's. Pat. You're giving a logic class now?
- [40:27]
C
Yeah.
- [40:28]
A
Okay.
- [40:29]
C
The che thing is driving me crazy. I'm like, this is atopic derm.
- [40:34]
A
No, it is not.
- [40:36]
C
It is. Here. You know what?
- [40:38]
A
I'll go.
- [40:39]
C
I'll go full zyrus. And don't ever. My advice to anybody. Never go full zyrus. Yeah, but my fool's iris is. Yeah, if my. My fool's iris is. If a. If you diagnose your patient with chronic hand eczema, you are a dumb and bad dermatologist because you have taken a whole host of medications that work really, really well for things that are atopic derm and taken them out of the picture and allowed your patient to get one FDA approved therapy. You diagnose that patient with atopic dermatitis. Hand exit, hand, predominant atopic derm. You have 12 medications, and when amlatilmab gets approved, 13 medications that you can give your patients that'll make their hand eczema better.
- [41:25]
A
Patton, that's actually reasonable. See, that's. You went full Cyrus. That's the most sense you've made to
- [41:33]
C
me because I don't feel good about this at all. I wanna. I wanna go take a hot shower.
- [41:43]
A
Cold shower. That's what you really mean. What's your next patent?
- [41:50]
C
I do not. Oh, we're skipping fares because she did, too. Okay, fine. Let's go. Brepo. Sitinib. Brepocitinib is an oral tick two slash jack one inhibitor. It's like a molecule that binds to both. It's kind of neat. It's like a horseshoe.
- [42:09]
A
This is insanity. That. This is nuts.
- [42:12]
C
Abstract Presented data from the Valor trial, which actually was published, I think the same day that Dr. V was presenting this data. This was a study 241.
- [42:23]
A
Is it Vloigels or Vlugels? I actually don't know.
- [42:27]
C
She won't talk to me personally, so I. I never get to ask her what her name is. So this was 200. 241 dermatomyositis patients underwent randomization. 30mg Brepo, 15mg Brepo and placebo. Primary endpoint was something called the mean total improvement score or TIS. Higher scores meant greater improvement. So 30 milligram breau group statistically significantly better than placebo, 46.5 TIS to 31.2. The 15 milligram group was numerically but not statistically significantly better than placebo. There were nine other secondary endpoints. I'm not gonna go through all those. The Breo 30 milligram group was superior in all of those nine endpoint points. There were two skin related charts. So I, I actually went through the New England Journal Medicine. This wasn't covered specifically in the little abstract, or maybe it was, but the two skin related charts in the New England Journal of Medicine article. The least squares mean change in C. Dassy, which we, we had a, a rheumatologist on and Matt called it the Cadassi and she laughed really hard at that one. One, I think. So the chain. The least squares mean change in c. Dazzy was -11.7 for breo versus -7 for placebo. In patients with moderate to severe.
- [43:53]
A
What do those numbers mean? Like, I have no sense. I know what like easy 75 means. I know what passing 90 means. What the hell was that?
- [44:03]
C
I think what she said when she was on is if like a difference of three or four, which that wouldn't seem like that much of a difference. Like that's, that's clinically meaningful. Okay, I, I think I remember her kind of saying that.
- [44:17]
A
Yeah. Yeah, go ahead.
- [44:21]
C
Okay. In patients with moderate to severe skin disease at baseline. So these are patients that had a C. Dazzy A Of greater than 14, 44% reached cutaneous clinical remission at week 52 compared to 21% of placebo patients. So big difference. Side effects, serious infections. That one kind of stood out. Serious infections occurred in 10% of the Breo 30 milligram group compared to 1% of the placebo. They made a note in the, at least the New England Journal article that they, they didn't have to stop therapy, they have to be treated through that. But it was classified as serious infections in those patients. So brepocitinib, I mean for a tough disease, a bad skin disease, these were patients with both skin and muscles. So it wasn't just skin. They didn't have like a clinically amyopathic dermatis myositis group in this study. But pretty, pretty impressive numbers. I'm kind of excited about this one.
- [45:24]
B
Yeah, the pictures looked really amazing since we're simple dermatologists. Pictures are good, but yeah, it looked, they looked really good. This is exciting. This is such a tough disease.
- [45:36]
A
Yeah, agree. This is like if there's a disease.
- [45:43]
C
Yeah. These were not patients naive to other therapies. Right. I mean, a lot of them were still on pregnancy, so it wasn't like a true placebo group. It was patients that were on other therapies that had failed, like ivig, Rituximab, like if they were naive to any other therapy that excluded them from the trial. So these were patients who were had, you know, been on therapy or currently on therapy through the study, but they just weren't responding to the therapy. So these were, these were the patients that we see. You know, they're on the Plaquenil and the Ritux and the IVIG and they're not getting any better. So this is pretty nice.
- [46:21]
A
Yeah, agree. All right, last one. Radmicobart. This is a next generation IL4 receptor alpha inhibitor. So binds to a different part of the IL4 receptor alpha than Doopie, has a higher affinity for it than Doopie. And they have finished their phase three studies. They're for ad. Their asthma studies are ongoing. Their COPD study, phase two is ongoing. But actually, so this is a drug that I've not been following terribly closely because I'm like, like, how much better could it be? And so it's, it's probably better than doopie. The 52 week numbers, 96.6% easy 75, 87.1% IGA 01, 85.3% easy 90. Now the 52 week data though is we don't have any comparator arm and I'm not certain if those are as observed numbers or if they are, you know, modified or NRI numbers, because when you see a number like 96.6%, like that usually means to me that there's something weird with the study. Like, like nothing. You just don't see numbers like that.
- [47:57]
B
So I'm, and that wasn't maintenance of response. That was actual response. It wasn't like, oh, if you had a PAs or EAs, see 90 at week 16 and you continued it was true response.
- [48:13]
A
I, I think like it's the abstract and I want to see like the whole paper and the whole thing. That would make way more sense if it was maintenance of response. Like it just, it's, it's hard to believe because whenever you look at Doopie and you say, okay, what if we give DUPY every week instead of every two weeks, it is statistically no better. And that shouldn't. If it was just that you're binding more if you double the dose. Like you should see a big thing. Maybe it is the fact that it's a different epitope. But yeah, I'm excited now to see the full article come out to, to really dig into this and see if I can figure out why they are somehow tricking me for how good this drug is.
- [49:14]
B
I like how they're probably tricking you. That's, that's, that's probably what it is.
- [49:20]
A
I mean I'm easy to trick. True, I'm easy to trick. I'm very. If I want to, if I want to believe it, I'll. I'll find a way to believe it. That's. This I don't want to believe, but I, I'm so far I'm believing it. Let me see here. I've got AI running in the background. Let's see if it will tell me if that was a maintenance of response or a total response. Let's see here. Come on. My computer's not running slow. There it is. That's what I need. Let's see. Based on the available reporting, total Response at week 52, not maintenance among 16 responses, ZAO the presenter framed it. Responses continue to improve over time with IG0 and 1 in easy 75 rising to 87.1 and 96.6 respectively by 52. And that language rising to implies a cumulative rate.
- [50:17]
B
It does.
- [50:18]
C
Okay, we'll see.
- [50:20]
A
Right.
- [50:20]
C
Did you have AI record the sessions?
- [50:24]
A
I was. It was how he was quoted in,
- [50:27]
B
you know, some other non dermatological or something like that.
- [50:32]
A
Yes. Okay. Yes, one of those spammy emails. All right, go fares, what do you got?
- [50:39]
B
Okay, I have intralesional PD1 intratumoral therapy. So this is a dose escalation study. So this is Int Ph762. So what is this? You're like oh, another interlegional PD1. It's actually a small inhibitory RNA that goes into the tumor cell and silences PD1MRNA inside the T cell so that it doesn't prove it doesn't express PD1. So interesting the different than an antibody binding to the surface and it is you know, in like a cholesterol backbone so that it gets endocytosed inside the the cell. So phase 1B dose escalate. They just basically did like dose escalation study and they looked at three different cohorts and they could have squamous cell carcinoma which was the Majority of the patients melanoma or Merkel cell, and they got weekly doses for four weeks and then they had their tumor excise and then they could look at things like pathologic response as well as clinical response. So 22 patients received the drug at different doses. There was, they did not reach like, oh, this is our, you know, our dose limiting. There's no dose limiting toxicity. So they could have gone higher. 20 of these patients had squamous cell carcinoma. 10 of them actually had a complete pathologic response. So no viable tumor. Four had a path partial response. There was a patient, one patient with Merkel cell who had a partial response and one patient with metastatic melanoma who had no response. If you look at the higher dose cohorts, they did look like they numerically did better. So when they used, you know, injectable resist response criteria, they only saw 15% complete response. But this is kind of what happens with, you know, sometimes with like more neoadjuvant treatment or intralesional treatment is that you get this robust immune response. So the tumor looks bigger and more inflamed, but it's really the immune cells that are in there, not the tumor. But this was, I thought, really interesting. So basically 50% of the cutaneous squam patients had a pathologic complete response. This is intra tumoral therapy. It should really only go into the T cells and you know, knock down their PD1 expression. So early phase. But interesting, interesting.
- [53:08]
A
This intra tumor stuff is going to be, it's going to be cool. It's going to be cool to see how good they can get it to be. I'm excited about the varic has got one come in. We did the, we talked about the sepal sep, some apple map. Some of the map one. I feel like my grandfather now, my grandfather could never say the word hippopotamus. I can't, can't say the names of any of the drugs. Now he'd be hip, hip, hips. Now I'm doing the same thing now.
- [53:40]
B
That's you.
- [53:41]
A
That's true. It's in the genes. So that's it. So for our listeners, you are now caught up on the real nitty gritty of everything interesting that happened at the AAD this year. least everything interesting that happened with, with the, the data for the drugs. I mean, there was a lot of interesting stuff that happened with me after 9pm but in terms of the drugs, you're all cut up. All right, well, I want to thank our listeners for joining us this week. I hope you learned a few things. Hope you laughed once or twice. And mostly I'm hoping you're planning to join us next week. And until then, I'm Matt Zyrus.
- [54:19]
C
I'm Tim Patton.
- [54:20]
B
And I'm Laura Farris. And we are Derms on drugs.
- [54:23]
A
It.