← Derms on Drugs
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- [00:03]
A
Welcome to a special episode of season three of Germs on Drugs, a video podcast brought to you by Scholars of Medicine. The best educational platform in dermatology and provided no cost medical providers. Germs on Drugs is where cutting edge dirt meets hit or miss comedy. I'm Dr. Matt Zers from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on a cutting edge of derm and you'll actually have some fun listening. New episodes drop every Friday in Scholars of Medicine, Apple Podcasts, Spotify and other major podcast platforms. And I highly recommend that you download the Scholars of Medicine app to access the full podcast video archive and explore the best derm educational content out there. Real free pharma independent coverage of everything that is exciting happening in the world of derm. There's a fantastic core curriculum if you're new to this, if you're relatively new to derm, and it is supported by an amazing AI clinical consultant called Ask Simon. So I mentioned that this is a special episode and the reason that makes it special, me, Pat and Ferris sat in on the late breaking abstracts at the aad. And if you don't know, this is like where all the drug companies try and they competing to get in their best new data. They have like a whole gazillion submissions and they have a panel that picks like the most interesting, coolest, hottest stuff and it's just all day on Saturday. So we sat in a dark room, watched this all day Saturday and we're going to tell you what we thought were the high points for late breakers. So let's go ahead and get into it. Dr. Ferris, kick us off.
- [01:47]
B
All right, so I'm gonna start with a. The abstract I'm going to start with was reflumalast and kids. So this is the Integum, an infant study. So this is reflumelast, 0.05% cream I E. Zorif cream in infants 3 to 24 months with mild to moderate AD. So this was an open label study. It only lasted for four weeks. They had to have at least 3% BSA. Mean age was 61 weeks, which I think is a little bit over one.
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A
That's impressive, Paris. That's good.
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B
Yes. Math on the fly.
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A
Math on the fly.
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B
So although they Only had to have 3% BSA. The mean BSA was actually 30%. But you know, they're little. That's still not a lot of cream. So how did they do? Among those patients, about half achieved an IGA of clear, almost clear at four weeks. And 58% of infants reached in easy 75. Um, and if you looked at two week data, that was 34%. So again, this was open label, so we don't have placebo numbers. Notably among those infants who had scalp involvement, like 2/3 of them achieved a scalp IGA success, like 0 or 1. So they made the point that this was anatomically even better in the scalp. Kind of fits with what we see with Z foam and scalp psoriasis.
- [03:13]
A
Agree.
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B
You know, they looked at things like, yeah, so you know, maybe there's something magical about this drug in the scalp. I thought maybe it was the foam. But since babies don't have a lot of hair, you can do the cream on the scalp too. You know, they did things that are like cute for me, not as a pediatric dermatologist. Like they've got like itch scores. You're like, how does a 50, a 61 week old baby tell you how itchy they are? But apparently the parents give you that score and you know, rapid itch improvement.
- [03:41]
A
Okay, how young did they study it down to?
- [03:46]
B
So they were down to as low as three months. So this is three to 24 months.
- [03:50]
A
So I do. I assiduously avoid taking care of young children. Is this, Are there any other ad drugs approved this young? Like is Ucrissa, but I mean, I don't really consider Ucrysa a drug. But is it approved down to three months?
- [04:09]
B
Chrysa is approved down. I don't know. I'd have to go look. It's approved down to a young age. I can't remember if it's down to three months or not. It's good because again, I also studiously avoid. I think that the only thing I would use is like protopic 03% or something is down to maybe six months. I don't know. Don't take my word on that. Look it up. But the babies did get interestingly most common adverse events, diarrhea and 3% or more.
- [04:37]
C
So I know that's the thing. Like kids, little kids poop so much. Like you do it one day and you're like, oh my gosh, diarrhea is a side effect. The, the Z is giving them diarrhea. Like I can see that.
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B
We don't know.
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C
Yeah, yeah.
- [04:52]
B
So it's true.
- [04:53]
C
But I could see that happening in real life if you're like, well, side effect of diarrhea. And after two applications, the parents will be like, oh my gosh. Yeah, this totally caused diarrhea.
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B
Right. But that's just what babies do.
- [05:05]
C
Yeah.
- [05:05]
A
Let's see. And I'm looking it up right now. According to AI, our cutest plan to submit the NDA second quarter of this year, subing standard 10 month review. It's probably early 2027 that this will become FDA approved and prescribable would be my guess. Okay.
- [05:24]
B
Right.
- [05:25]
A
We need it.
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B
But not by any of us because we don't see anybody.
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A
We hate seeing kids.
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C
Don't see kids.
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A
We don't like kids.
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B
That's right.
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C
Yeah. Don't even care. Don't even care about kids stuff.
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A
Both of you have like a lot of kids, right? Pat, how many do you have?
- [05:40]
C
I have like 13 kids.
- [05:42]
A
That's what you're Catholic? That's right.
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C
I have four boys.
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A
So you will be depending on somebody to take care of you when you're old because your boys will do nothing.
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C
Yeah, right. My sons are not gonna help me.
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A
Yeah. Fairs. How many you have? Three. Fairs.
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B
Three kids, two girls. I'm in good shape.
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A
Yep, you're good. You're good. Okay. I got. I got two, but they're both girls, so I'm in good shape too. Okay.
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C
Yeah, fair. Can I borrow one of your daughters? That sounds weird. Never mind.
- [06:16]
A
All right, Patton, what do you got?
- [06:19]
C
I. The first one that I took was from the AM session. Molecular Signals in Skin Aging. So tape strips were collected from the face and inner arm of 156 patients whose age ranged from 20 to 85. Actually, we should kind of say so that the integument infant. That was one presented by Lawrence Eichenfeld. Who the hell. And then I did this. Who the hell cares? Because they worked hard. Molecular signatures of healthy skin aging. Highly potential interventional anti age targets using state strips. That was Helen. He.
- [06:55]
A
All right, so I'm glad you're doing this one because I paid no attention, don't care. But most people care, so I'm glad you're doing it.
- [07:01]
C
That's not nice. Yeah, they work. They should get some sort of columns.
- [07:05]
B
Not listening to this. Yeah.
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A
All right.
- [07:08]
C
156 patients whose age ranged from 20 to 85. And RNA seq analysis was performed. Molecular signature of aging containing over 1200 genes was identified. Skin aging was associated with. With increased melanogenesis. I mean, that's Not a surprise. NF Kappa B pathway activation increased inflammation. Not a big surprise there. Increased oxidative damage, decreased collagen. I mean everything you would expect. Kind of interesting. They, they, they reported differences by race. And so blacks and Asians increased cornified envelope genes. Black skin was the, had the most significant downregulation in lipid synthesis. Asian skin genes that regulate reactive oxygen species senescence earlier immune activation peak. White skin increased inflammation more than the others. Females had increased androgynization compared to males. Like a change, I want to say like between sun protected and sun exposed. So the, the kind of, what they were getting at is with this individualized skincare recommendations. That's where I wasn't sure. I mean, you know, reactive oxygen species, inflammation. If you put on sunscreen, that'll probably help take care of that. Apply antioxidants. That's probably going to be across. You know, no matter what your tape strip says, I don't see the recommendations really changing that much. So I don't know, I'm not sure what the, you know, ultimate application of this will be. But I mean kind of a neat study I thought does suggest maybe sort
- [08:42]
B
of differed by age. Like there was like this acceleration of changes in the, like in the 40 to 50 group relative to like the 20 to 30 group, right?
- [08:51]
C
Yeah, right. Like that was where the big changes seem to happen. Like in the 40 group and that's where you saw the biggest difference between that group and like, yeah, younger than 40, that's where you saw the biggest differences.
- [09:02]
B
So it was all intuitive 50 people to tell me that.
- [09:07]
A
But yeah, yeah, I thought I wrote, I remembered earlier this year there was, or maybe last year there was some research in general for aging that there were like two state. Aging isn't like a smooth thing. It's like you age a lot in like your 40s and your 60s or something. Like not so much and then you hit 40 and then you're kind of okay through your 50s and then like 65, you start aging fast again. I think I remember seeing that somewhere. Or I could be making it up.
- [09:38]
C
Either way I, I could definitely see like some cosmetic derm spa person being like, we will individualize your skin care regimen. We're going to do this tape strip. It's going to cost you $1,000. It probably costs like $5 to do. And then they'll put together a regimen that it will cost an additional $3,000. Like I could see it.
- [10:03]
A
You're right. That sounds like a good business model to me. Yeah. All right, let's move on to mine. So I'm going to talk about. I actually don't even remember the name of it. It's the Amla Telemab study which is the Sanofi's ox 40 ligands blockade which was advertised heavily, heavily at the meeting. So basically this is a fully human non depleting OX40 ligand monoclonal antibody blocks OX40 ligand, which fundamentally this conceptually is totally different from any biologic that we have because it's not blocking a cytokine, it's blocking the co stimulatory signal between antigen presenting cells and memory T lymphocytes. And that is an upstream effect that can block lots of cytokines did this. So both it and Rokatinlumab, which is this one box to Oxford ligand rokatinlab binds to OX40. So the basic takeaway here, the data is not impressive. So it's not, at least at 16 weeks, not as good as dupy, it may pick up steam later. The main potential benefit is that it may lead to a long term alteration and trajectory of disease. So if you do well on it, remission, remission or even even cure, although that's pie in the sky. But the problem is we're never going to know because none of us are going to prescribe it because it causes cancer. So this was a well known thing. So first there's cancer studies looking at stimulating this pathway which is like, oh say if you got cancer, we're going to stimulate this and it's going to cure you, but if we block it, no problem. Right. So specifically the cancer that it causes is Kaposi sarcoma and this was a well known thing. Like I, I was stunned whenever I found out that companies were developing this because it's a well known thing. Human herpes virus 8, which is what causes Kaposi sarcoma, OX40 pathway plays a very important role in suppressing it. And so if you've got HHV8, human herpes virus 8 and we block this pathway, probably it's going to activate and you're going to get Kappa Z's and son of a gun, it turns out that is the truth. So I do hope this comes to market because we do need additional options in somebody once they have failed Doopie, Adbri, Ebglis, Rinvo, Nimluvio and Sabinco, after they have failed all of those, then there would be a good role for this one that causes cancer. So that's where we will leave it. I would anticipate in each city there will be literally one dermatologist who prescribes this drug and they'll have like four people on it. But it might also have lots of other indications. So that's the other beauty of this pathway. It should work in vitiligo and alopecia areata and psoriasis and lichen planus and pretty much any inflammatory disease you could think of. So that there might be more to it than we would think. But main takeaway, probably not as good as doopie causes Kaposi sarcoma, but might give a long term cure. That's where.
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B
Because it specifically targets activated T cells.
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A
Right?
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B
Activated T. It's. Yeah.
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A
Yes. It targets activated memory T cells.
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C
Yeah.
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A
Yes. All right, next Faris, what do you got?
- [13:37]
B
Okay, this next, this next presentation was on Res pal des leukin.
- [13:43]
A
You know, I think of this as the, think of this as the Rumpel Rumple Stiltskin drug.
- [13:48]
B
Yes. We're going to call it Res Peg, which as did the presenter, David Rosemarin, because nobody could say that name throughout an entire presentation. Anyway. What is this? It's an IL2 receptor. It. So it's an antibody that targets the IL2 receptor complex to stimulate regulatory T cells. So it's not like, as opposed to your OX40 ligand drug that is depleting or inactivating activated T cells. This actually stimulates the regulatory T cells, you know, the cells that won somebody the Nobel prize in medicine this year. Okay. By activating these, then you can actually bring the immune system back to balance. So that's, that's sort of the mantra of this drug, as you may have guessed, because it has peg in it. It's pegalated. And so that gives it an extended half life.
- [14:39]
C
First time. I really, I would not have guessed.
- [14:42]
B
Okay. Resolve AA study. This is a, a randomized control trial. 92 patients got randomized to one of two doses of ResPeg or placebo. Primary outcome was 36 week. Week 36% reduction in salt score. So on average these patients did have know moderate to severe AA. So salt scores at baseline was around 80. So 80% of their hair was gone and about a third of them had a Salt score of 95 to 100. So these are like the, the people who basically have no hair that we know that these are the hardest people to get a response in. At week 36, the respeg group had a 30% reduction in their salt score, whereas the placebo group only had an 11% and about 15% of the entire population that was treated went down to a salt score of 20 or less, whereas that only happened at 6.7% in the placebo group.
- [15:43]
A
15%.
- [15:46]
B
So, so the average improvement in salt reduction in salt score in the res pay group was 30%. Okay. Um, however, among the group who did respond, 15% of them had an assault score of 20 or less. Okay, so they had a good response.
- [16:08]
A
So no, this is no JAK inhibitor.
- [16:12]
B
Well, it's week 36, right. That's not like the Jacks. Phenomenal.
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A
30% ish people to salt 20 at 24 weeks.
- [16:23]
C
So that's what I had.
- [16:25]
B
Yeah, yeah, yeah. Okay, you're right. So it is not a JACK inhibitor. But you know, I guess the question is like, might this have a little bit better durability given that what you're targeting are the regulatory T cells? Right. So could this have off drug effect?
- [16:43]
A
And so it's, it's both the plus and the minus, right, that it's not a JAK inhibitor. So like, look, dermatologists have shown like we prescribe O Tesla. That makes us the worst doctors in the world. Right? We, we prescribe a drug that does not work, is terribly tolerated, but we don't have to do any labs or talk about any side effects. So if you don't have to do any labs or talk about any side effects, we don't really care if it works is what we have shown as dermatologists. So this. Well, yeah, I'm obviously trying to make. Try to be a smart ass.
- [17:15]
B
A jerk. Yeah, we know. So speaking of side effects, they did point out that there were no in. There were no, there was no evidence of increased mace. There were like no mace thrombotic events. There was not like a high rate of, you know, malignancy, Jack signals, infections, things like that. They did notice some eosinophilia in the res peg group. Nothing really stood out. Adverse event rate in the resp group was a little bit higher as 97% versus 70% in the placebo. They did also notice some improvement in eyebrow and eyelash growth, but they didn't see any in the placebo group. So suggesting that there could be something there. So might it be effective but slower? And the, you know, the, the results did not like, they had not plateaued. So they were still sort of going up at the end of the study.
- [18:04]
A
Didn't like 70% of people get injection site reactions.
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B
I think that there was a pretty high injection site reaction.
- [18:11]
A
That's what. Because I, yeah, I looked at this somewhere. Else, like a ton of people.
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B
I kind of blow that. I sort of blow that off, but yes.
- [18:19]
A
Okay.
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B
Was it.
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C
Don't. Weren't T regs studied? Like, in the cancer world, where if you gave mice a bunch of T regs and then gave them cancer, like, their cancers were way worse because you had all these T cells basically shutting down the immune response, like, that would be my concern here. Like, you are expanding.
- [18:43]
B
So. Worried about malignancy? Yeah.
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C
Yeah.
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B
I mean, because this is not targeting specific regulatory T cells. It's going to target all.
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C
Yeah, yeah.
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A
So.
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C
So if you had a basal cell and you got res peg, I think the basal cell would go crazy.
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A
Oh, my God. Whoa. So 0.0001% would die instead of 0.00001%.
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C
So then make it melanoma or squamous cell.
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A
Okay, fine.
- [19:14]
B
Yeah. Injection site reaction rates were like 91% of patients on res P. But interesting. 30% on placebo, which. Who knows what was in that placebo?
- [19:25]
C
I think he said, like, it doesn't. It's just like, it's impressive to look at, but the patients don't complain of pain or itch. I think that's what he said.
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B
Erythema. I don't know. Injection site reactions don't really get my hackles up that much.
- [19:37]
A
So if they just. For our listeners, there's some interesting. There's some interesting old data that if you want to stimulate T regulatory cells, you also can just give people low dose methotrexate. That's one of its primary mechanisms of action, is stimulating T reg cells at low doses, higher doses, I think it does all kinds of stuff, but that's just interesting older data. All right, let's move on. Patton, what do you got?
- [20:04]
C
All right, my next one is the efficacy and safety of dursamelagon and epp. This was presented by Amy Young. So EPP patients have a defect in the final enzyme of heme synthesis. Guys, remember that from residency? Ferrochelotase.
- [20:20]
A
Oh, yeah.
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C
Which chelates the iron into the heme molecule. It's also the enzyme that doesn't work as well in cancer cells. That's why PD is more cancer cells specific, because Protoprofora 9 like builds up in cancer cells because they don't have that. That ferrochelotase enzyme doesn't work as well. What was.
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A
What was the name of this drug again?
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B
Review ever. Go ahead.
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A
Yes, it is.
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B
Yeah.
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C
What's that.
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A
What's the name of the drug again?
- [20:43]
C
Dursum Melagon. That's how I'm saying it.
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A
So wait, that's a character in the Lord of the Rings, right?
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C
It is. He was the. The head L. I have no idea.
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B
Sounds like one losers.
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C
It could be easily. Yeah. So X linked protoporphia is also due. Well, not also, but it's due to a gain in the function of like one of the first steps in heme. So EPP and xlink protoporphyria, they both have the issue of building buildup of Protoperion 9, which makes them very photosensitive. All right, so dersamelagon is an oral MC1R agonist. It stimulates melanocytes to make eumalanin, which absorbs visible light. The study presented was a randomized placebo controlled phase 3 trial. Patients 12 and older were given oral duressamalagon or placebo. Primary endpoint was the average daily sunlight exposure time to first prodromal symptom and it was increased in the Dirsi group. I'm calling it dirsi. Secondary endpoints of global impression of change. Number of sunlight induced pain events. Non prodromal phototoxic reactions were all better in the Dirsy group. Side effects, as one would expect, hyperpigmentation and moles, you get increased nevi. So it's, it's kind of a treatment that works similar to afomelanotide, which is also FDA approved to treat EPP and xlp. That's an implant that you get like every three months or something. And it's like a peptide analog of melanocyte stimulating hormone. So kind of the same effect that an MC1R agonist would have. Although the alpha melanotide is less specific. Just kind of cure. You know, I'm getting all these emails for EPP and xlp. This was one of the drugs. Why I think I'm getting that the. There are some other ones by top per bytopertin and port 77. So we're gonna like getting these new drugs for EPP, which I mean I've only seen one case at like a grand rounds. I think when we went down to West Virginia or something. The I, I, that was not.
- [22:51]
A
He's not kidding.
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C
West Virginia. I don't want emails for what we.
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B
Literally one in Pittsburgh too. Also.
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C
Okay.
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B
Residents, they have like the fluorescent diapers, right?
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A
We used to go down.
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C
Yeah.
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A
We would go down to remember that
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C
EPP is not in the urine.
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B
Oh. Oh, yeah. Okay. No PP Robin Garrett.
- [23:12]
C
So actually for the residents or anyone out even attending, listening, if you think your patient has ep xlp. The screening test is free red blood cell protoporphyrin. That is the test you order. That's how you screen. And if that's positive, then you do the gene testing to see whether they have the ferro ketase ferruchelitase deficiency or they have that a. What did I say it was? ASA, alas. 2 gene deficiency. Really cool. So.
- [23:40]
A
Right.
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C
I mean, just neat science. Interesting aside. Was that the presenter? She's a pulmonary and critical care medicine attending, I think at Massgen. She actually has epp.
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B
So now we've seen two people with epp.
- [23:57]
C
That's true.
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B
There we go. I was right. It was two people.
- [24:01]
A
So these have got to be the dumbest companies imaginable. So they're studying this drug for a ridiculously rare disease when what they should be doing is asking Abbvie to purchase the company and bring it to market as a combo treatment for vitiligo.
- [24:20]
C
Right.
- [24:20]
A
You give them a little. You give them a little.
- [24:23]
B
Or to be tan or full of nevi. Yeah, right. Like, what have I always wanted? I wish I were Molier and Tanner.
- [24:31]
A
I wonder if you could get a mole in just once if you like injected it intra lesionally.
- [24:36]
B
If you wanted like the Marilyn Monroe
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A
beauty mark right there. Right.
- [24:40]
B
Oh, yeah. No, I don't want to make fun of them. It is good to have people working on drugs that can help rare diseases and I think it's kind of cool,
- [24:49]
C
but it's not like it's somewhat incompatible with any sort of normal life. Yeah, right.
- [24:58]
A
Yes.
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C
Yeah, yeah. So. So any help that these people.
- [25:02]
A
That's the commercial market for this drug should be in Vitiligo. Vitiligo combined with the JAK inhibitor. Speed it up. Speed it up.
- [25:08]
B
If you keep. It's. It's an immunologic reaction against the melanocytes. I don't know that you can do
- [25:13]
A
it, but it's a better to use it with Rinvoak. So Rinvoak to protect the melanocytes and then this stuff to like kick them in the ass and get them proliferating and migrating.
- [25:26]
B
Okay.
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C
Because the. The biggest.
- [25:28]
A
Yeah.
- [25:28]
C
Renv. Vitiligo treatments take forever. Like you tell the patients you'll be better, but it may take two and a half years, right? Yep. Okay. Maybe something like this.
- [25:39]
B
Hopefully they're listening. Hopefully they're listening.
- [25:41]
A
Okay. All right, let's move on here. My next one was Kate, so my next one is actually what Patton's wife will be known as in 20 years when the AIs are running everything. KT621 is Patton's wife's nickname is KT
- [25:57]
C
for he's that far down on the list.
- [26:00]
A
There were 620 before her. KT21. KT621 first evidence demonstrating clinical activity and safety. So this is the breakthrough in my opinion for atopic dermatitis. So this is a stat 6 degrader. So you take it and it basically makes your stat 6 get metabolized and broken down. And so it is basically the equivalent of a JAK inhibitor but with a perfectly clean side effect profile so far. So as far as we know like amazingly clean side effect profile. And to when I look at the efficacy I think jack efficacy. So 30 milligrams of Rinvo, 200 of Abro but with a clean safety profile. So I cannot remember the name of the company. Chimera. It's Chimera. Chimera. If I was a healthcare investor I would which I do not ever invest in anything healthcare because that would be insider trading. But if I was, I would be trying to get money into Chimera because this stuff is going to kill it. So just super effective drug, really interesting science first like degrader of a protein that I've ever seen. So just cool drug and I have no conflict of interest with Chimera but I'm trying to get one, trying to get one but don't have one yet. So Chimera, if you're listening, great drug, good work. All right, all right, move on to our next, our next one. Fares, what do you got?
- [27:32]
B
Invuticitinib in psoriasis presented by Andy Blauvelt. So what is Invuta Sitinib. It's a next generation allosteric tick two inhibitor. So you can think about it as like next, next generation. So TIC2 it provides, you know, each one of these has like a little claim to fame. Maximal inhibition of tick 2 over a 24 hour period. So studies were two parallel phase 3 studies, onward 1 and onward 2. And they were head to head studies with both a premolast and placebo and, and vasitinib 40 milligrams twice a day. These were typical psoriasis phase three, you know, Pazi 20, BSA 25% BMI 30 kind of people. Okay, what did the data look like? Pasi 100. That wasn't really their primary endpoint but it's think the most exciting primary endpoint. P100 scores were in vuda citnib 29.4%. What's that?
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A
Not bad. Not bad.
- [28:35]
B
Yeah. 29.4, 27.7. There's two parallel studies. A premast that was like 4 to 8% and placebo was less than 1%. Actually maybe P100 was their primary doctor. Ignore me, that's at week 16. At week one. At week 24 it gets a little bit better like around 40, 41% for invuda sitinib and it still hadn't plateaued at that point. A premolast, it was 8 and a half and 13%. So I thought that was, you know, pretty good. They did show scalp data. 75% of patients had a scalp IgA of clear or almost clear clear. About 48% in the premolast group did. And they, you know, showed better itch reduction within Buddhist, better DLQI01 scores. Safety, they had higher rates of nasopharyngitis and acne and interestingly actually headache. So about 10% of patients on in buda sitib had headaches and that was actually higher than what was even seen with the premolast. No death, no mace, no TB, no cytopenias, no significant lab abnormalities. So another type 2 inhibitor, but one that seems to work better. That's a pretty decent PASI 100 response rate so far.
- [29:55]
A
2 thoughts here. Number one, like scalp, genital, all that stuff when people are like difficult to treat sites. So far, as near as I can tell, every single drug that has ever been studied in a difficult to treat site works just as well in the difficult to treat site as it did in general psoriasis. Meaning that they're not actually difficult to treat.
- [30:18]
B
Am I missing for patients to have? I guess.
- [30:22]
A
Oh, so maybe not difficult to treat. Maybe more just like high impact.
- [30:27]
B
Yeah, I, I think of them a little bit more as like high impact sites. Now that being said, a 01 of 48% with a Premalast for the scalp. I mean that's better than what we see for like 01 for a premalast on the body. Right? Y So I, I do think that there's little differences. It's funny, I was just looking at this for another thing I was doing and you know, there's things like palmo like if you look at the. Geez, what am I. I'm blanking on the iotide at their special site data. Like they did well on the scalp, they did well in the genitals, but like palm oil plantar or what they call hand foot disease, which we assume is palm plantar, didn't really reach statistical significance. So I don't think that they're all created equally.
- [31:17]
A
Okay, interesting. And it's affairs. Just foreshadowing. I hope you're going to do the Zasso data and when you do the Zaso, I want to hear your thoughts on which one of these is going to be a better drug. But we can wait till we get to the Zaso.
- [31:31]
B
You're just going to have to wait.
- [31:32]
A
We'll wait. All right, Pat, Pat. And what do you got?
- [31:35]
C
All right, this was another rare disease, recessive dystrophic EB. So the. This was ABCD5 cells and recess, recessive dystrophic EB. This was presented by. I can't read because this is so Kirill Dimitrov. All right, so RDEB patients, they have biolic defects in the collagen 7 gene. Just like a horrible disease. Right? We all know this is terrible. They showed three pictures and one was like a young kid and it looked like he or she had like no skin from like the neck down. Mitten deformities, like terrible therapies are limited. We actually covered one of the therapies in one of our prior episodes. So there's vilsuvas, which is like a plant derived gel. There are two gene therapies, Vijuvic and Zevaskin. We covered Zeva skin and that was where they took the patient cells and they transfected them so that they would make collagen and then they, they made sheets of these transfected keratinocytes and put them in wounds. I mean, the, the results from that study was pretty impressive. So anyway, this is just maybe another therapy. So abcb5plus refers to a subpopulation of human skin derived mesenchemal stromal stem cells that express ATP binding cassette sub, sub family B, member 5. That's what ABCB5 stands for. When these cells are administered IV, apparently they can have these anti inflammatory effects and I guess that's the point of these cells. It was a phase 3 placebo controlled trial. Patients either got 2 million of these cells on days 0, 17, 35, and at month 3 and 5, they're followed out to month 6. Patients receiving the stem cells had improvement in wounds and a decrease in inflammatory markers like IL6 and stromal cell derived factor 1 alpha. So I mean, that's pretty much it.
- [33:26]
A
I could not figure out the science of this at all. I was like, why, why would. You're still not going to make any collagen 7?
- [33:36]
C
Yeah, right. I didn't quite Understand it either. And it was like, okay, well these cells are helpful for wounds. So they're not fda, they're not approved anywhere to really treat anything outside of. I was reading that there's this center in Germany where you can put them into like chronic venous ulcers and because I guess these chronic wounds have these high inflammatory markers, these cells like given systemically tend to migrate to these chronic wound areas and they take these pro inflammatory sort of environment and they calm it down so that eventually you would heal. But. Right. I mean it's not like, it's not like the cells turn into keratinocytes that can make collagen 7. So I don't know. Yeah, it's, they're, they're all, they're allogenic, like they're from a non RDEB donor,
- [34:33]
A
but still they're not going to make any 17.
- [34:36]
C
I, I was confused. I thought it was something, oh, these cells make collagen 7. But it didn't seem like that was the, it seemed like it. I, from what I can gather it was this technology was felt to be something that can help heal chronic wounds. And so they've been looking for, they've been looking for patients with chronic wounds and RDEB patients certainly get that.
- [34:59]
A
Okay.
- [35:00]
C
Yeah.
- [35:00]
A
All right, moving on. My next one was Zuma Licobart. Zoom Zoomy Locobar. Zoomy Locobart. So for short we're all going to call this one Zoomy and think about little tiny dogs running around the house like crazy after dinner when the little dogs get the zoomies. So Zoom Zoomie is a extended half life IL13. So we're all going to be hearing a lot about this mechanism. So basically Apogee and it has a sister company called Aruka. They take basically existing antibodies. So I think this one is like basically Lebri that they make this yte amino acid thing that makes it bind to the neonatal FC receptor. And what that does when the antibody binds to the I think the liver cells normally it gets taken in and chewed up. And that's why antibodies have a half life. When it binds to this receptor, it goes into the cell and then it gets recycled and spit back out. And so this is an extended half life. You can basically think of this stuff as EB glis with a 77 day half life. So it'll be likely a might be a Q3 to a Q6 month injection is probably going to be somewhere in there. The question is, you know, when you look at their data, I, my guess is it's not going to be any better in terms of efficacy than Lebri or Doopie. The data looks very similar to me. The main benefit is going to be you'll only have to get a shot, you know, two to four times a year. But the concern for me is, you know, we know DUPY causes arthralgia. That can be awful nuanced psoriasis, it can reveal ctcl and if you give a. We haven't seen much of that with Lebri so far but it might just be that it's too early. If we have the same side effects from blocking IL13 as we get from blocking IL4 and IL13 then with this extended half life it could mean that oh, if you get the arthralgias or the psoriasis with a red face, we're going to stop the drug and it's going to take a year and a half for your side effect to resolve because of the extended half life. So it's, you know, it's going to be interesting to see what this drug is going to like, what their data is going to play out to be. If the extended half life, fewer injections is worth the in potent, possibly increased risk of side effects being long term or the conjunctivitis for example, we've got the conjunctivitis, maybe it's going to be a year and a half. So it's, it's an interesting thing. I think. I'm not sure that this is the perfect thing for ad drug, for the ad drugs that we've got. But psoriasis, this stuff is going to be kick ass. That is, is very true but. So that's, that's pretty much it. Extended half, basically. Extended half life. Libry and I can't decide yet if I think this is going to be good or bad but they're starting their phase three up late this year. So it's probably still three or four years out before it gets to market.
- [38:24]
B
Did they have data for things like psoriasis or arthralgias that, did they see that or conjunctivitis or anything but it's, it's small and early.
- [38:34]
A
But yeah, I think, I think this was maybe their. I can't remember if this was a phase one. I think it was a very small number of patients from what I remember because this is the first data I've seen for it. So it was a small, let me see here. I think I've got the numbers of patients here.
- [38:53]
C
It was a phase two, 123 adults, 123 adults.
- [38:56]
A
So, right, you would only expect to see two or three cases of nuanced psoriasis. So if you saw none, you wouldn't like, that's 50, 50 chance you would see none, essentially. So, you know, we'll find out in the phase three. We'll find out in the phase three.
- [39:14]
B
Just starting up the phase two one. I'm here. It's basically like Skyrizi with the same modifications. So, you know, that would be potentially, you can treat psoriasis once a year, once every six months. I just don't know how much, you know, I mean, I'm interested in it. I'm wondering if we'll have, you know, other like impacts. IL23 we think is important for maintaining memory T cells, so maybe blocking it very, very consistently will help to have more of a remote effect. I think it'll be interesting, but I don't know if patients, if you're like, here's a great drug, but you have to inject it four times a year or you can have this twice a year. Like, do they care? Is that enough?
- [39:58]
A
I think the bigger thing with their iO23 is that they are giving it like triple the dose of Skyrizi. So I am anticipating that literally 100% of people will get 100% better. Like if. Because it's, you know, there is data as they did what the knockout study, if you give people a massive dose of Skyrizi, basically all of them get better. So like n, you know, now we get what, 75% to Passy 100 or something or Passy 90. I don't know. But I think because they're going to give such a massive dose, it might be better. That's the.
- [40:37]
B
Might be better.
- [40:37]
A
Yeah, might be better. All right, what do you got, Ferris? What's your next one?
- [40:42]
B
Okay, my last one for this episode is zupatib and vitiligo vi up. Yeah. So two was two phase three studies of upavacitin of 15 milligrams for non segmental vitiligo. 48 weekend point. Primary outcomes were tvazi 50. So it's like a 50. The vazi is like the vitiligo pazi. T is total and F Vazi 75, which is facial vazi. So what percentage of patients had a 50% improvement in their total VASI score and a 75% improvement in their facial VASI score? 300. About 300 subjects per each study. So 600 total. A little over 600. About 20% of patients on UPA achieved TVAZI 50 versus about 6% on placebo, and about a quarter achieved the FVAZI 75 versus 6% on placebo. Responses again, looked like they had not plateaued at 40. At week 48, it did hit all its secondary outcomes, like patient and physician, global impression of change. Usual Jack side effects. Acne, uri, no mace, no vte. Because these are generally like younger, less obese patients. There were a couple cases. Disaster. You know, I think, you know, this probably is not actually, like, as good as what we see with topical ruxolitinib. And. But I would also say, like, you know, in real life, I would use this with UV light with a little heliocare. You know, these are mono. Maybe with even, like, a topical steroid. But these are monotherapy studies, so maybe there's room for improvement here. And it was the UPA 15 milligram dose. They did not look at going up to the higher dose to 30.
- [42:35]
A
What did you. Sorry, did you say what their facial. How many people Got F V? 75.
- [42:43]
B
Yeah, that was 25%.
- [42:48]
A
Oh, that is not a great number. At 48 weeks.
- [42:52]
B
Yes.
- [42:54]
A
Yeah, that's definitely not as good as Otesla, I think, which would kind of make sense since high. Not a Tesla. What the hell is it? I think Opsura does better than that. I don't know if it does a ton better. I think it gets a third of people there at 48 weeks, roughly. So. But, yeah. Interesting. Okay. All right, Patton, what do you got?
- [43:17]
B
Yeah. Yeah,
- [43:21]
C
that's a good question. What do I have? I think I moved in. I'm moving into the afternoon one. So. Early. Early.
- [43:27]
A
Early. Memory loss. Is that what you have?
- [43:30]
C
I've had that for a while. It's late at this point, by the way.
- [43:35]
A
Had a great joke this week in honor of Easter. Whole line of rabbits. Whole bunch of them. 30 of them, and had them hop backwards. What do you. What is that called?
- [43:51]
C
Hairline retreat?
- [43:52]
A
No, a receding hairline.
- [43:55]
C
Yeah. Oh, gosh, that's so close.
- [43:58]
B
Yeah. All right.
- [43:59]
C
Anyway, I thought you were gonna say one of the benefits of having Alzheimer's is you can hide your own Easter eggs.
- [44:09]
A
We're cutting that, actually. No, we're not. It's patting your.
- [44:12]
B
No, keep it there.
- [44:13]
C
I'm suffering from it. I think I'm allowed to make jokes about it. All right, so mine was. Or desiccumab. This is an anti IL15 medication.
- [44:25]
A
This is exciting.
- [44:25]
C
It was given. This was a study looking at vitiligo. Yeah.
- [44:34]
A
Yes.
- [44:35]
C
Yep. Okay.
- [44:37]
A
You're losing a lot of credibility here, Patton. Yeah, a lot of credibility looking at. I can't remember what they were studying.
- [44:45]
C
The thing where you lose the pigment, it's the vitiligo. This was presented by Brett King. So in the anti IL15 medication is given subq 300mg every two weeks for six doses. Primary endpoint was F. Vazi 35. At week 24 there was no significant difference from placebo. So this was 40 patients that got the orab or desicumab however and then 20 patients that just got placebo. So the primary endpoint, week 24, F Vazi 35, no difference. Any patient who didn't reach the primary endpoint got narrow band UVB until week 48. And so the OR sikumab light arm did better than the control light arm. The numbers aren't listed in the abstract and if they were in presentation I didn't take any photos so I. Wait, you so you did. So I guess you deplete CD8T cells. That's what I. I'll. That's what these anti IL15 medication does is it depletes these CD8T cells and then you can give UVB and the CD8 cells won't be around to attack the melanocytes.
- [46:00]
A
I don't know patent by so the reason you didn't. For anybody who doesn't know Pat and the reason didn't take any pictures, he actually has a jitterbug phone. Doesn't even flip. It was pre flip phone case. That would be a step up in his tech.
- [46:21]
C
I have a Google Pixel, thank you very much.
- [46:24]
A
Okay.
- [46:24]
C
Just because I'm not Apple, you guys are such.
- [46:28]
A
I can't believe I get screen texts from you. It's awful.
- [46:33]
C
Your phone stops?
- [46:34]
A
Yes.
- [46:35]
C
I'm not giving. I'm not giving into the peer pressure. I'm my own man.
- [46:38]
A
Okay. Fair. Okay. All right. Throughout my so that's disappointing. I was excited about this I.O. the I.O. 15 drug for vitiligo. Disappointing shoot. Was hoping for better. All right, last one for me. Villobelumab. Vilo bellumab. Sounds like a beautiful antibody. Anything, anytime there's a Bella, it always makes me think beautiful. So vilo belumab. Treatment for a very ugly disease. Ulcerative pyodermic anguinosum. Results of a multicenter randomized placebo controlled phase three trial. And this is a cool drug. So it is an anti C5A. So it blocks some part of your complement cascade and seems to have very little immunosuppressive Effect. So now you don't make neutrophil extracellular traps, and that should help with piderm gangrenosum. And it seemed to. So people had about 80 to 90% reduction in the volume of the ulcer, but placebo had about a 40% reduction in the volume of the ulcer. And now that wasn't really placebo, though. It was active control. So everybody got 20 milligrams a day of prednisone at the start of the study. And then they had a required weaning. And it was just shocking how well the placebo group did, to be quite honest. But it looks like the drug does something. It's just a matter of we don't know. It's like PG is a hard disease to study. Like it's a hard disease to study. Think this drug does something. It'll be interesting to see if it. If they develop it further. I think they're also studying it in HS where I've heard that it is very good preliminary efficacy. I'm going to throw this out there to Abbvie or to Aruca. One of you should be studying IL23 inhibition for pyoderma gangrenosa. And then instead of us all, then when we complain, oh, you guys charge so much for these drugs. They're whatever. But we did a study in people who have this horrible disease and there's only like this many of them. See, are we ethical? Yes, yes, you are. But, you know, so I want to see the IL23s get in on this disease, but if they don't, they'll the. This drug will hopefully go further.
- [49:21]
B
You want them to get in on the aisle just for the sake of having an aisle 23 indication or do you have some mechanism of action that makes you think.
- [49:28]
A
It's been preliminary. So there, there are reports, a number of case reports, and I think even some case series of aisle 23 for PG and it works. I actually think it'd be a better thing for Aruka to study using the ultra High Dose IL23 because I think that would probably work great.
- [49:52]
C
One of the things that you can do though is say that I'm really not sure if this is cutaneous Crohn's or PG.
- [50:02]
B
Oh, there you go.
- [50:05]
A
Right. Because TNFs work great for this stuff. Oh, yeah. But Sky Reese is a proof of Crohn's too, huh? Yeah, yeah, yeah, I forgot about that. Okay.
- [50:14]
C
And there is a JAD article within the last two years about like a Delphi consensus of how do you diagnose cutaneous Crohn's. A bi, a skin biopsy is not one of the major criteria. So you could tell the insurance, like according to this group of experts, I the skin biopsy that I did, yeah, it doesn't show those granulomas. That is not one of the major criterias that this Delphi panel came up with. This could be cutaneous Crohn's. I just don't know. I'm not, I'm dumb. I'm not a good dermatologist. And that's very, anyone, any insurance person that's talked to me knows that that's totally believable. I'm dumb.
- [50:48]
A
And it's, well, it's good. It'd be a good, you know, you talk about this group of experts said if anybody ever quotes terms on drugs, they're going to be like and these three idiots said, sorry, we're the, we're
- [50:58]
B
the anti Delphi consensus panel.
- [51:04]
A
The Delphi non on that note panel,
- [51:06]
B
we're the dummy consensus panel.
- [51:10]
A
I want to thank everybody for joining this week, joining us this week for AAD late breaking abstracts. And join us next week. We're going to cover another group of late breaking abstracts. So if you want to be on the cutting edge and know what's coming in the field with no baloney, join us again. So we hope you learned a few things. We hope you laughed once or twice and mostly we're hoping you're planning to join us next week. Until then, I'm Matt Zyrus.
- [51:37]
C
I'm Tim Patton.
- [51:38]
B
And I'm Laura Ferris. And we are derms on drug.