Best of AAD 2025: The Hottest of the Hot Dermatology Data

[music] Welcome to Derms on Drugs. A video podcast brought to you by scholars and medicine, the best educational platform of dermatology, and totally free. Derms on Drugs is where cutting edge derm meets at her mis-comedy. Mad Cyrus in each week, I'm joined by my residency buddies, Dr. Laura Ferris and Dr. Tim Patna, where we use our 60 years of combined derm experience to discuss, debate, and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of derm, and to be the most fun you've had while actually learning something useful. New episodes drop every Friday on scholars and medicine, Apple podcasts, Spotify, and any other somewhat major podcast platform where you might get them. Alright, so let's go ahead and jump into our special post-AAD episode where we are going to get into our favorite late breaking research, and I'm going to kick it over to Dr. Ferris to get us off the ground. Alright, so I am going to talk about the iconic lead study. So this was the first release of results for the Phase III study of the targeted oral peptide that blocks the IL-23 receptor called Icochirachinra, which has something that kind of means IL-23 in Greek. So this was a Phase III study. So I have talked before about the Phase II study. I do kind of like this study, so I promise this might be maybe my last time talking about it for a while, but this is the Phase III. Icochirachinra 200 milligrams once a day, which was not in the earlier phase studies versus placebo. So primary endpoint at 16 weeks, then patients who were on placebo did cross over to the Icochirachinra. So this was adolescents and adults, but mostly adults in the study. So they actually presented Week 16 and Week 24 data. So these patients were kind of typical like psoriasis clinical trial patients, BSA around 25%, about a third of them were bio-experienced. So what were the top line results? Pazzy 90 at Week 16 was 50% of patients interestingly at Week 24. That went up to 65%. Pazzy 100 was 27% at Week 16, but 40% at Week 24. IGA 01 was 65% and then it was 74%. So kind of similar to what you saw in the Phase II, but maybe a little bit slower to get to those results. They also had scalp specific IGA. So 01, clear, almost clear 80% of patients who came in with scalp disease were clear, almost clear at Week 24. Nothing new, safety wise. So you know, I think this is interesting. I think it's going to be interesting to see how this works in special sites, psoriatic arthritis, all kinds of stuff. You know, it was kind of bold to go forward with the dose that they had not looked at in Phase II, but it just seemed like it worked as well as BID dosing, which I think is going to be important for an oral drug. Do you think the results will keep getting better when we go out to 36 weeks and at this point, what existing drug would you say it's mo-- if I-- I keep in my head like here's how good I think. What would you think it's most at the moment just efficacy wise? Yeah, so I don't-- we talked about the Phase II data and the closest I came was Cocentix, but maybe this is-- this data you would say this looks like Cocentix but slower, but it's once a day oral drug. Yep, okay. All right. Looks good to me. All right, Pat, go ahead. All right. Efficacy and safety of oral duke, gravacitinib and patients with cutaneous manifestations of lupus, arthematosis results from paisley, CLE, a global Phase II randomized double-blind placebo controlled trial data was presented by Victoria Worth. I didn't even know that there was a study in 2022 that looked at duke and SLE. That shows you how much I'm in the literature. I'm involved. They had some skin cores in that study, but this study, the paisley, CLE study, was specifically looking at cutaneous lupus. Patients could have systemic, less fewer than 50% of the patients did in this particular study. Adulter randomized in a one-to-one fashion placebo, duke or 3-milligrams, BID, and duke or 6-milligrams, BID. There was a crossover from placebo at week 16. The primary endpoint was mean percent score change from the baseline in CLASI-A at week 16. For placebo, the mean percentage change was 28.4%. For the two duke groups, it was better, 47 and 50, for the 3-milligrams and the 6-milligrams respectively. Secondary endpoints were mean improvement from baseline and then CLASI-50. They were also better for duke group. CLASI-70 was a post-hoc analysis and that was better for the two duke group. The CLASI-70 numbers were odd. The placebo group, like 15.9% reached CLASI-70. The lower dose duke, 3-milligrams, BID, it was 49.5%. So 15.9 for placebo, 49.5 for duke or 3-milligrams, BID. That's a huge difference. The higher dose duke or percentage was lower. It was 29.5. It was like 20% difference. The p-value was 0.273, I guess, not statistically significant. That 70 data was weird, but overall, looks like duke group could be a good option for CLE patients. I included a little -- there was actually a review about small molecule biologics in lupus. There was a meta-analysis and duke group came out on top. I mean, granted meta-analysis and all the things that go along with that. But -- So duke group, yeah. It's hard for me to get that. Like, duke is a pretty effective drug, but like if you're going to study something that's expensive, why not study the Jacket Hibiter that's going to be -- but I get it. I guess I get it. Better, maybe, better, more acceptable safety. I mean, it does -- it does make sense that it's the interferon alpha pathway, right? So it totally makes sense for lupus. And I'm looking at -- I was at that blightbreaker. Like, the pictures are pretty impressive. Like, you know, sometimes you look at lupus studies, you're like, "I guess that works." But you're like, "That looked better." I guess that's true. I have no sense of what classy 50 looks like, right? You have a sense in your head what classy 90 looks like or easy 75. But, yeah, classy. We're not used to any end points in. Okay. All right. We're going to move on to my first article. This was QY201 in adults with moderate to severe atopic dermatitis, 12-week results from a dose finding phase 2 trial. So here's what was interesting. This is a Jack-1 tick-2 dual inhibitor. So this seems that it would be the equivalent of giving somebody both subbincot and so tick-2. So, right. So, Bincot is highly Jack-1 selective. And obviously, so tick-2 is a tick-2 inhibitor. So 200 patients, 1-1-1-1-1, 50 people in each arm. And what was impressive, this had by far the best results I've ever seen for any study. So if these results are reproducible in phase 3, they're highest dose, 20 milligrams BID, got over 80% of people to EZ75 in 12 weeks. Normal data, so like high dose, RINVOG gets about 70% of people there. So this is meaningfully better than high dose RINVOG. They got about 70% of people to IgA01. Again, in RINVOG, that number is more in the 50 to 60 range. So this would be the, if these numbers were real, it would turn out to be the most effective thing we've got. And it makes me think maybe some of my super challenging patients, maybe the key thing to do is have them on subbincot, which has appeared Jack-1 inhibitor and given some so tick-2 samples on top of it or something. But we'll see. But that was just most impressive data I've seen. Any comments? No, I think it's going to be interesting to see where these drugs end up and who knows, maybe that'll also work in things like lupus. I think we're just seeing the tip of the ACE barricone. What this combination can do. It's interesting just that we're not, we still haven't really seen a whole lot of progress in atopic dermatocacy from when Dupy came out. It's just interesting on how different it is from psoriasis. And usually things work better in phase two than phase three. So we'll see you have this phase three. True. All right, Dr. Ferris, let's go on and give us our tick-2 inhibitor update. Okay. Tick-2, the molecule of the podcast. So this, so I'm going to just quickly go through three. So first one, efficacy and safety of ESK 001, a highly selective oral tick-2 inhibitor, moderate to severe plaque psoriasis, phase two results, presented by Andy Blowvelt. And so basically the dose that they looked at was, you know, was 40 milligrams BID. sort of the pharmacokinetics behind that was that while so tick two, you know, has partial inhibition of tick two activity throughout a 24-hour period, this their claim is with this dose, you know, 24-hour full inhibition of tick two. So maybe it'll work better. So what did they see? Pazzie 75 at week 12 was 64%. They did, they had an open label extensions of we look at week 52 data that Pazzie 75 response was 77.5%. Pazzie 90 61% Pazzie 139%. So how is that, you know, it's pretty good if you look at to do the matzirus, what how does it work like so tick two? Pazzie 75 similar for so tick two is 72%. So so tick two Pazzie 90s about 45% versus for this drug is about 61%. Pazzie 100 is not really published for so tick two. I think it's, I think I've seen it presented and it's sort of, I mean, I guess it's around, it's like around the 20% level. So don't quote me on that. So about double that Pazzie 100 of 39%. So, you know, it kind of kind of interesting that, you know, there's a lot of people working on tick two inhibitor. So there was another one. It was inventus bio from China D 25 70. So patients randomized it, you know, three different doses. And basically, if you look at Pazzie 75 in that group, it was like up to 90% versus placebo was 12%. Feel like at Pazzie 100, they were 39 to 50%. Pazzie 90 70 to 77%. So also looking pretty good. And then it's hard to understand. So if, if the idea is that the one right before this, the ESK drug is above the whatever threshold for 24 hours, how the hell could another drug be meaningfully more effective? Yeah, it's hard to know. I mean, I don't know if it's hitting. You know, one could argue one might be less selective. One might be more selective. You know, I think they're all allosteric inhibitors. But yeah, bioavailability. I mean, you know, who knows? Like those are generally in vitro things. So, so that was kind of interesting. And then the, not last one was I know care pharma, which is also Chinese ICP 488. And so they had, you know, Pazzie 75 results that were like 78%. They're Pazzie 90s were like 35 to 50%. Pazzie 100 was more like 11%. So I would say this is a little bit more like so tick two in efficacy. So lots of, you know, development around tick two. We'll see which one wins. Yeah, that's it. So be an interesting race. Hopefully it's on a race to the bottom. Hopefully it's a lot of energy. A lot of energy. A lot of investment. Yes. All right. Dr. Patten, let's go on. Do the doopee for BP? Yeah, efficacy and safety of the Pilibeb and patients with bulless, hemphagoid results from Liberty BP adept phase 23 study data presented by Fredrick Carl. I'm not sure if you pronounce that ex. He was French. He was very French. The design of this trial was published in advances in therapy at March 24. And so that's kind of what I would show during this slide. It's a double blind placebo controlled 52 week study of doopee plus steroids. I think it's very important. I mentioned it was doopee combined with steroids, dose in a very specific and well controlled way. And adults with moderate to severe BP primary endpoint was proportion of patients achieving sustained remission at week 36. It was a tough endpoint, right? Patients had to be in complete remission. So no active disease at week 36. No steroids after the initial taper at week 16. No relapse once steroids were discontinue. No rescue therapy through week 36. They had to meet all of those endpoint. And it was reached by 20 about 20% of patients on doopee versus four on placebo. So that doesn't seem like a huge number. But I think that primary endpoint was challenging. Were they using any topical steroids? What? Do you know if they were using any topical steroids? I don't. I want to say it was probably not allowed. But I don't know that for sure. Yeah, probably not. But I couldn't I couldn't find anywhere. I look. Yeah. Yeah. There were other endpoints greater than 90% improvement in BP diet, peak, peritis scores that the doopee group did better at cumulative prednisone dose was mentioned. It was kind of interesting. And the doopee group, it was 1,678 milligrams lower over 36 weeks. That works out to 6.6 milligrams a day if I did my math, right? It doesn't seem like that much of a difference, but maybe over 36 weeks that would be a huge difference. I don't know. Do you know what the average prednisone dose would was for the people who were done on it? Like how much of a reduction was that? Yeah. They did present that, but it wasn't in the little abstract. And I'm not one of those persons that takes a picture of every slide that put up the thing. Not a nerd like Ferris. I love that. My camera rose full. It's very well. It's very odd looking. I don't know. It's dystopian to me. Everyone's pretty. I have that confidence. We're good. So I think doopee will help physicians manage BP patients. But you know, when you have BP patients, you're like steroids will get the suddener control. We know this. How do we get them off steroids? These are old people. They have comorbidities. If 80% of the patients are still on steroids, did you really like kind of get you to your main goal? And you know, with retuximab out there, which may allow us to do it better. I don't know, but doopees easier to administer. Side effect profile is nice. I think more people will use it. It'll be interesting to see where doopee fits in for the treatment of BP. I just I don't know. I think it will help us manage these patients. But yeah. But people know how on like a high enough dose to clear and then say, now let's taper or did you have to they did do that. They did come to totally clear on steroids. So six weeks of of corticosteroids like at a moderate dose to shut BP down. I can tell you from seeing a bunch of BP patients that have been managed by other dermatologists, nobody does that. Nobody keeps their their patients on 30 or 40 milligrams of prednisone for six weeks. That was how the study was done. And then they tapered it more rapid than I think what you would have done in clinical practice. But I think they had to to see if doopee worked. You know what I mean? So maybe there's room for this like with slower tapers and would do we have any idea how doxycycline and in medicine work in BP like is because that would be the obvious combo is put upon that in doopee and it's all very safe and blah blah blah. I'm tying flammatory matrix metalloprotein nine inhibition by docs. I mean, I don't think we know. Okay. Fair. Fair. So do you think this will be like seeing the picked I don't if they had pictures of the thing or whatever you but they're going to show you the best pictures. So who who the who the heck knows if I have you used much doopee off label in in Bempoquay? I decent amount. It's it's plus minus. I mean some people absolutely respond and other patients, you know, they come back and they're like, I stopped that shot. It wasn't doing anything like I still have all these blisters. Yeah. It'll maybe a Tesla of BP. Or maybe they'll find biomarkers. So in the erdicarious space, it looks like there are it's going to be definable like this will be a good doopee patient. This won't that data should be coming out pretty soon. Yeah. All right, we're going to jump on a mine which I I love this idea. So three phase adaptive clinical try to evaluate the human factors of patient-led patch testing protocol for the diagnosis of allergic contact dermatitis. So this is one of the most timely interesting things. I think I've seen somebody really try and do. So the basic idea here is they have this thing called the patient journey which is like the patient. I don't know what they're doing. Answering questions something. And it helps individualize allergen selection. And then rather than putting like 80 or 100 or 120 patch test allergens on somebody's back, you put 20 on and both you know 10 on each of their roller four arms. And then they develop the app that the patient then after they take them off in two days. Two days later they do this AI deep learning visual thing to interpret the patch test spots. And so I will tell you literally nowadays with camp 2.0 the contact allergy management program from the American Tech Derm Society and AI between those two things most patients once they figure out what their allergic to can probably figure it out themselves. And this you know if you're just testing people to 20 allergens you could literally be like hey put this app on your phone. You know do the stuff for the next month and come back or tell us what to test you to we'll put the test on and go on your way and enough to come back again. It could make it so much more patient friendly. Now you're not going to get into like occupational cases and stuff like that. But for routine patch testing this could be a really big breakthrough. And I You did go back and look because as a patch tester, you always talk about where you want to put it on their back because that's where we developed all the allergens for in your skin's different in different places. There've been a few studies looking at that and it, it, not a ton, but a few like literally two or three. And it does look like putting allergens on your volar for arms is fine. You don't get too many false positives or false negatives. So this, this is feasible. I'm interested to see where it goes. I don't, you know, I don't think it's time you go out and start doing the Morrow, but next year this could have developed to the point where we're able to do it. So one question from this, because I, I thought that through this and I was like, I thought it was kind of cool for the AI aspect, but like half of these patients had an allergy to propolis. Yeah. So what, what's up with that? So that was the, with propolis, which for our listeners, propolis is a component of beeswax is basically theoretically processed out of the beeswax and whatever come from the pollen, that kind of stuff. But you see a ton of propolis patch test reactions. If you're patch testing full panel, and in my opinion, the vast majority of them are false positives. They are real positives, meaning there is clearly a reaction on your arm. And it clearly looks like allergic contact dermatitis. But I just, I never saw clinical relevance to it. It can be a marker for fragrance allergy and theory. It can be a marker for beeswax allergy, but I never really saw any clinical relevance to it, meaning I didn't see the people get better. But that's, you're right on the money. It's, it, it, you saw a lot of positives, but I think they were not truly indicative of allergic contact dermatitis. All right. All right. Let's go into our next one, Dr. Ferris. All right. My last one that I wanted to talk about was totally different. This was laser assisted drug delivery to treat non-melanoma skin cancer. So I just thought this was cool. This was not like, and this was, you know, sometimes like you get all these big, farma studies. I also like this was sort of a single center training program where they present, they did this study and presented it. So biopsy proven basal and squamous cell carcinomas that were under two centimeters. They had 30 cancers and 23 patients. This was not a randomized study, but what they did was they had this dual wavelength, and I'm not a laser person, but not a blade of laser, which I kind of know what that means. And so they treat, they did like a little pulse with the laser, 15, 50 and 19, 27 nanometers. And then with a one to one and a half centimeter margin, then they put, um, Turbinebulin, which is claciri on first dose in the office, then they had them do it for four more nights at home. And then they saw them back in like rebiopsy and re evaluated at one, six, then 12 months. And so what was kind of cool was like, there was a 100% response rate. These were, you know, there's their skin cancers that were lower risk. They bend, shape biopsy, but they did like the, and they showed pictures like the cosmetic outcome looked really good. And you know, the moderators said, well, you should have done, you know, laser alone, Lycereal alone. And then the two together should have been a three arm study. I totally get that. But, you know, kind of an intriguing idea that maybe there are ways that we can deliver drugs and we can do things more creatively to do to deliver, you know, topical agents into skin cancers, whether it's laser or injection. And, you know, I think deserves more, more work and also kudos to like, you know, people in training for doing clinical trials. It's not always easy. And being up there against, you know, the big pharma companies. Why the hell they have to use a laser? Why couldn't they have just used like a, or a hyphurcator and like, okay, here's some terminal fuel to put on there. Yeah. I mean, I think that the idea is that that kind of targets your, your, you know, like these little, like, like little holes, but not, you know, not obliterated into like, you get an epidermal and dermal penetration. So it sort of lets you open up and target drug into those areas. Yeah. Could you maybe get this another way, like, like the little smallpox vaccine things that they used to use? Like, maybe there's another way to do it, but probably a bunch of that laying around. We got a bunch of them. Exactly. Right. Knees and stomachs, smallpox is probably going to come back. I'm really one old enough to have gotten vaccinated against smallpox. My mom tried to get a fine doctor to give me smallpox vaccine, but they weren't given it anymore. She was actually just trying to give you smallpox. She could tell early on. Yeah, exactly. All right, Pat, and what do you got? All right. Also, skin cancer, PD1 directed, intratumural immunotherapy for cutaneous carcinomas, interim results from an ongoing study of intacil pH 7.62, data provided by Mary Spellman. It is intacil pH 7.62. It's a proprietary compound by phyopharmaceuticals. It delivers a silencing RNA. Silencing. To sell through some sort of spontaneous delivery, which I guess is kind of a unique for SIRNA technology. The self-delivering molecule enters the cell. In this case, it would be a T cell. It's used to an RNA silencing complex risk, RISC, which then goes and finds the messenger RNA that is going to make the cell make PD1. It destroys that messenger RNA so that T cells won't express PD1. It serves the same function as a PD1 blocker. Patients got four doses of intratumural injection over three weeks and then underwent surgical oxygen two weeks later. Six patients with SCC, two complete responses, two partial, one of which was like a 90 percent. Two non-responders. For intratumural stuff, is this good? Is this bad? I don't think we really know. Small study. One patient with metastatic melanoma had no response. Just a kind of a neat molecule, I guess, but I don't think we have any big intratumural data out of the PD1s or anything like that to see how these numbers compare. No, we just have to. Do you have ongoing trials and there's been some early phase data for intralesional submiplimab for basal cell, carcinoma, and squamous cell? I think that the response rate was better than this for intralesional submiplimab. We got that TVEC and then two more TVEC stuff coming. I got a little stuck on one of the slides I was reading it and I was like, "Cos it shows the two strands of DNA and then it's what is the GUIDE strand?" I was like, "GUIDE, I've never seen what's GUIDE." Then turns out it's just the guide strand. Yeah, and it's RNA. Yeah. Okay. Moving on to our last two here. It's getting late in the podcast. All right. So initial results from the signal AA study randomized. We'll see if we can control phase 2A trial of BEMPIKA BEMPIKA BABART. Sure. BEMPIKA BART. You got it. You got it. You got it. IEL7TSLP, Bifunctional Receptor Intagonist and Patients with severe spherospherialitis. So basically, this is a monoclonal antibody that blocks that binds to one thing, but kind of like Stilara, binds to one thing, but blocks to this binds to one thing, but blocks both IEL7 and TSLP. And basically, it turns off autoimmune T cells without having much effect on normal T cells. It's the basic idea. So it does seem to have some element of blocking response to a totally new antigen, but it doesn't really mean a suppression. You don't see people getting opportunistic infections. This is a very small study. 44 patients kind of a proof of concept. In the salt, 20 scores were not great, but I could tell you that as an investigator, it's really hard to enroll this trial because the Jax had just come out. So everybody with alopecia areado was going on Jax. And what was really shocking was that there are a number of patients who continued to regrow, get better and better for six months after the end of the study. So this could be our first biological phrylopecia areado and it could be something that really has a long-term effect of turning around the autoimmune process. So it's an interesting new mechanism of action. They're going to be pursuing it a number of other things, including Vidaligo. So right, two diseases, we don't really have any biologics in yet, but just an interesting the long-term effect was what was coolest. And then the other study, similarly, the long-termness is what's important here. So this is Roca-Tinlemab. This is an amgen molecule. So Roca-Tinlemab significantly improved clinical size and symptoms by targeting oxporti, receptor positive T cells and patients with moderate-sphere topical metitis, results from the phase three rocket horizon trial. And so this is a monoclonal antibody that targets the oxporti receptor and blocks, oxporti and oxporti ligand from co-stimulating each other, reduces memory T cell population. regulations. This was basically a normal atopic term study except the end point was 24 weeks instead of the usual 12 or 16 and The results were not like mind blowing so easy 75 they got about 33% of people at week 24 IJ 0 1 versus placebo got 13% IJ 0 1 they got 19.3% Versus 6.6 for placebo. I'm gonna tell you my experience when the trials I thought the drug worked better than this In the trial so but the the big takeaway is it had not plateaued at 24 weeks and there are because of its depleting memory T cells There is real belief that this could be long-term disease modifying where you take this for six months or a year and then you're able to be off therapy for Long periods of time perhaps indefinitely So that's kind of the interesting thing the other cool thing with this drug or interesting thing Small number of patients, but I say small maybe 20% will get fevers and chills After the first dose and it's pretty impressive like whenever they come back and tell you about it They're like growing up in bed like shaking and sweating Which I'm wondering if that's a marker for efficacy if those people you know have a better outcome But nobody's cut the data that way yet, but so this just an interesting new pathway that will be on the It's on the horizon for a topic germ and again the main benefit doesn't seem to be rapid efficacy. It seems to be potential for long-term remission Is the big takeaway? I don't either if you have any Comments on either of these I Think that's I thought the pick-up art or however you say it study was super interesting and it's T. S. L. P Say you could imagine like it's maybe not just a topic or you know that could work in a topic That could work and you know, it's interesting for a a the safety look good and you know again like we talked about Jackson and A a like six months is still kind of an early end point, right? So yeah, yeah, no I agree in this and you're right So this has both because I'll seven is more in the TH1E pathway So this has got kind of a TH1 and TH2 slant to it and so really is broad what it could work in I think they're going after Some pulmonary indications as well. Maybe you send a phylicusophageitis that kind of stuff maybe BP Maybe BP maybe we'll finally get something all right That sums it up for the late breakers that we hear at Derbs on drugs slot. We're the most interesting this year at the AAD so Thank you for joining us if you've got questions comments ideas for topics We should cover on the show shoot us an email Questions at Derbs on drugs calm again questions at Derbs on drugs calm and we hope you learned a few things We have to laugh once or twice and mostly we're hoping you're planning to join us next week Until then I'm Mads Iris. I'm Tim Pannan. I'm Laura Ferris and we are Derbs on drugs