Betsey Zbyszynski: Thanks for joining us today. I am here with Dr. Todd Schlesinger, a Dermatologist. We’re gonna talk about some psoriasis protocol design, obstacles and challenges, and what we see for the future. How you doing, Dr. Schlesinger?
Dr. Todd Schlesinger: I’m well, nice to see you.
Betsey Zbyszynski: Yeah, you too. Would you like to so a brief intro of yourself before we get started?
Dr. Todd Schlesinger: Yeah, sure. Hey, I’m Dr. Todd Schlesinger. I am a Dermatologist here in Charleston, South Carolina. Been conducting clinical trials ever since I was in residency at Cleveland Clinic. We have a practice called Dermatology and Laser Center of Charleston, it’s a private practice. There is also a research center called Clinical Research Center of the Carolina which is the entity under which we conduct our clinical trials. Been involved in many of the psoriasis trials to date and some of the medications that are now on the market. We are excited to have been participating in and continue to be involved in development work for future studies. So I’m looking forward to speaking with you and about all the new developments.
Betsey Zbyszynski: Yeah, great. Psoriasis is still a very hot market. A lot of new orals being tested as well as some topicals. What are the common obstacles you typically see in a psoriasis protocol design?
Dr. Todd Schlesinger: So in our trials in psoriasis studies the most common obstacles we see in protocol design have a lot to do with the inclusion/exclusion criteria. Many of them require subject to be naïve to other treatments. And in some case the biologic or other treatment that are on the market. And so, we see less and less patients now who are naïve. Because of the depth and breadth of available treatments now on the market, I think, what do we have? 11-12 maybe approved medications now?
So fewer and fewer folks are not under treatment or have not received or don’t have access to. So we tend to look in many cases to a more underserved population that maybe still doesn’t have access to medical care. So that’s one thing. Which is understandable.
The other thing is that the subjects that typically are looking to be in studies oftentimes have comorbidities that are excluded. So again, we’re looking for relatively healthy subjects for trials ’cause we don’t want to see a lot of adverse events. The companies are looking for clean outcomes and clean research. And many patients that have a more severe case of psoriasis also have comorbidities which if it doesn’t exclude them just on first glance they may get excluded during the screening process. So, the most common reasons people screen-fail in study, in studies are laboratory failures, or EKGs or, oftentimes just the inability to attend all the visits.
So those are the most common things that we see that are obstacles in design. It’s mainly lack of available subjects. They’re out there, some places there are more than others but I think as we have more approved medications it does increase the enrollment challenge.
Betsey Zbyszynski: Yeah, and what I found too lately, patients are so much more educated about their disease state and medications that may have worked for them, may have not. So , the enrollment can be challenging in psoriasis.
Dr. Todd Schlesinger: Yeah, they are. And with everybody being so busy now with the unemployment rate being low, I think in this time with pandemic sort’ve slowing down and people are sort’ve getting busy again, they don’t have time as much that they used to for the studies. During the pandemic they had plenty of time but then when they couldn’t come in due to the pan, you know, we were open but they were less likely to wanna come in. Now that everything’s kind’ve back to normal again or close to it people are busy. So they have jobs, traffic is higher again so coming to appointments is a challenge for them.
And also the other barrier in many cases to studies and people joining them is placebo component. Whether or not there’s a rescue component to that, I mean, good clean data means we get people through the placebo period. Placebo control period without having rescue therapy. Some case it’s necessary. So that can be a challenge.
And then also if you have a study that doesn’t have an open label extension. Many do, which is really nice, it’s good data. But on the other hand it’s expensive to run open label extension studies. But oftentimes that can be a bridge to approval for patients so if they can be told that they’re gonna actually get on active therapy after a period of time it’s, especially if they have severe disease, then it’s more enticing to the subjects to enroll.
So you know, number of reasons, there’s a lot of nuances and, and different protocols. As we get new medication and of course our biologics are very safe, if we branch out into other areas where there’s more risk for adverse events then that may become a barrier as well, but I think those are the main things that keep us from enrolling as quickly as we’d like to in our studies.
Betsey Zbyszynski: Yeah. Completely agree. What is a recent development in psoriasis that has surprised you, and why?
Dr. Todd Schlesinger: We’re very [00:05:00] happily surprised with the depth and breadth of efficacy that we’re getting with our newer medications. It was really nice during some of the early sort of a mid-phase of biologics when we kind of went from good to great. We had our first few drugs that were on the market, they worked pretty well. And then we started getting newer ones that worked really well. And I think that we’re seeing a refinement here in our injectable drugs that work really well and have sustained results so that was really nice to, nice surprise.
Of course now we are looking toward oral treatments, oral therapies that are gonna have similar efficacy as biologics. And that’s very helpful. And I think all that just comes from the constant innovation that our biotech companies are doing to bring us new molecules, new targets. Our biotech firms are a lot better at identifying and exploiting new targets than they used to be.
Betsey Zbyszynski: Yeah.
Dr. Todd Schlesinger: That gives us a higher chance of finding a very targeted molecule that can give our patients excellent efficacy with high tolerability as well. Which is what they’re looking for in good control. I think the holy grail is gonna be for medications that can actually give sustained benefit without actually continuing the medication, maybe not a cure yet but a remission off-therapy. So-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: Of course, most of the medications that we have require continued therapy to achieve long-term control. And they do very well. So, what’s gonna give us long-term without having to stay on medication. And that, may or may not be possible due to the inflammatory nature of the condition but you never know. That’ll be kind of nice.
Also it’s nice to see some of the topicals coming along. Those developments have been helpful in actually getting good control without having to take systemic medication. So those-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: Those are nice surprises. Why we know really going into the topical trials just weren’t sure what the outcome was gonna be. ‘Because each one of the molecules has it’s Achilles heel if you will. Each one of them has their own little side effect that we look for you know, [laughs] that we sometimes see in higher numbers than we want. But I think that’s manageable.
Betsey Zbyszynski: Yes. For instance, Dermavant just got theirs approved and I think Arcutis is next, right?
Dr. Todd Schlesinger: They, they-
Betsey Zbyszynski: For their topical-
Dr. Todd Schlesinger: They’ve actually got their drug approved as well, yeah.
Betsey Zbyszynski: Oh, yeah, So there’s now two… for moderate to severe two, I think, right?
Dr. Todd Schlesinger: Yes. Yeah.
Betsey Zbyszynski: That’s great.
I mean, for those patients that don’t wanna get a shot or take a pill every day, you know?
Dr. Todd Schlesinger: Yeah, and it’s a bridge also to systemics for those patients who kinda on between. So it’s gives us something to offer them besides topical steroids, topical vitamin D, combination of treatments that we’re used to giving our patients which if they can see early efficacy, they’re, they’re going to be more reluctant to actually stay on therapy. So we have to establish that trust relationship with the patient. And then actually seeing an outcome. And then they’re gonna trust the medication, trust the provider, trust the system. That kinda thing.
Betsey Zbyszynski: Yeah. Can you recall when you last changed your mind about a new approach to psoriasis?
Dr. Todd Schlesinger: I think there’s a resurgence in the benefits of thinking about using light therapy. So I think that for a while , for phototherapy, we got away from it. But I think I’ve changed my mind in understanding that phototherapy is very helpful for our patients. It’s more of an access issue than anything. But there has been an improvement in the availability of home uh, narrowband UVB units now. Several firms offer them in various sizes and shapes and forms for our patients. So that can be a nice addition.
There was a time when biologics were becoming popular we really saw a downturn in the phototherapy treatment that we were doing but I think that’s coming back. I’ve changed my mind about that and now I’m offering it more to patients as an adjunct to their other treatments as well.
Betsey Zbyszynski: Are patients open to doing the phototherapy?
Dr. Todd Schlesinger: They are. I think that the home units have made a big difference.
You know, if we can control their treatment delivery, we can deliver in a safe way. I mean, their are many UVB’s that safe. So I think they’re amenable to it at home if they have room for the device. And depending on what psoriasis they have. I think that it’s hard to get them to go to the office and of course, it may be hard for them to get covered on their insurance as well. So, I think they’re more amenable to home narrowband UVB therapy than they would be to lightbox therapy in an office.
Betsey Zbyszynski: Yeah. Hmm, interesting, yeah.
So, here’s a question for you. The year is 2027, what is everybody talking about in psoriasis?
Dr. Todd Schlesinger: Well, I think by then, I’m hoping that we’re gonna have a little bit better genomics. So we’re gonna have a better understanding of the genetics of psoriasis and how to manage our medications with respect to the gene profile. So I think gene expression profiling will become more and more prominent. We’re using it for melanoma, using it for squamous cell carcinoma. But in our inflammatory disease states , I think that will be more important for us.
2027 isn’t that far away from now really so we may see a few more biologics but given the long lead time to get something developed I mean, we may have a few new drugs available by then but, I can sort of see with my research, I can see what’s kinda coming down the road. So I kinda know what’s gonna be coming around then, but I think that we may see [00:10:00] more widespread use of gene expression profiling in inflammatory disease states in a general sense which may help us better select therapies for a patient.
And of course, we’ll get better at targeting. We’ll get better at molecular development of molecules. The creation of new molecules and identification of targets in psoriasis. We may see a few surprises, who knows? But I think by then we’ll see good incremental improvement from where we’re at right now. Will we see revolutionary change between now and 2027? I don’t know. I think it’ll be good. I think it’ll be evolution not so much revolution. But, you never know.
Betsey Zbyszynski: What about those combination JAK [inaudible 00:12:17] products or molecules that are currently being tested?
Dr. Todd Schlesinger: Yeah, I think those are great. And that’s something the folks who are doing the studies and who are looking at the posters of the meetings are already seeing some of the data coming across from those that’s been publicly available. Which is positive so I think those are gonna be a nice addition. Like we’ve seen for atopic dermatitis where there are approved medications now. And-
Betsey Zbyszynski: Yeah.
Dr. Todd Schlesinger: The topical that’s approved also for atopic and for vitiligo. So you already have JAKs in widespread use in dermatology now. So yes that’s incremental improvement in the efficacy for the orals that we’ll see soon.
Betsey Zbyszynski: If you could allocate $250 million dollars to any dermatology indication, which would it be and why?
Dr. Todd Schlesinger: Well, that’s a loaded question. I feel like 250, it’s a good amount of money but in the research world it’s not that much really [laughs]. So it’s really enough to maybe bring one drug to market. I think there’s a huge amount of unmet need in skin cancer. Especially in mild to moderate skin cancer where we’re doing a ton of surgeries on folks even though it’s an important thing to do. I think that if I were able to come up with a non-invasive treatment for skin cancer I think that would be something I would look into. You know, a lot of the other disease states that we see, that are being looked at are rare. There’s a lot of orphan diseases that effect patients in a very high way but a smaller number of patients are effected more severely so some of those severe diseases, epidermolysis bullosa. You know, things like that, that are very severe in a small number of patients. I think that I’d love to see improvement in that because those people suffer greatly with those diseases.
Betsey Zbyszynski: Yeah.
Dr. Todd Schlesinger: But then on a bigger scale, skin cancer is seven, eight million cases a year. Costs the system a lot of money. So if there’s a way to improve the outcomes there while still allowing the dermatologist to be at the forefront of that care, I think that might be something, maybe even a device or something like that. Or an injection, who knows? But I think that would be something I would like to see come to fruition in our space.
And also you know, just… some of the disease states that we see everyday, I mean acne, it’s still a huge problem. You still don’t have great treatments for it. We’re getting a lot better at it. But I think a novel treatment for something like that which is widespread and disfiguring. You know, would be important as well.
So, common things being common, I’d put the money where it’s most effective. Where it can be most used.
Betsey Zbyszynski: Yeah, and especially acne in the younger population it can do so much to their emotional state also.
Dr. Todd Schlesinger: I think the hardest thing is gonna be if I was a pharmaceutical company or an investor with 250 million would be, I’d be looking at the reimbursement market pretty heavily and the PBM system. Because I would be disappointed by investing a large amount of funds in something to get developed to only find it’s not reimbursed and not used. So-
Betsey Zbyszynski: Right.
Dr. Todd Schlesinger: I feel there’s a balance there between making sure that we’re not overspending in the medical care, so you always wanna have good cost effective, improving the value to the system as a whole to make everybody’s life better. But in the other hand you wanna treat, you wanna be able to get access to medications on the market.
Betsey Zbyszynski: Yeah, understood. So the last part of our interview today, I’m gonna do an overrated or underrated segment. So I’ll list a couple of topics and then you can say, “They’re overrated”, or “They’re underrated”. And just a little description of why.
So I’ll start off with, let’s see… how about the microbiome movement.
Dr. Todd Schlesinger: I think it’s underrated. think the microbiome is something we just don’t understand well yet. There’s a lot more research going into it. I’ve thought about it for a long time. Bacteria are such a huge part of our lives. Basically there may be more bacteria cells in our bodies than there are tissue cells. So it is a huge component of ongoing research.
Whether altering the microbiome on the surface of the skin will really make much difference, I’m nor sure yet. So, in that case it may be overrated, it may be too much hype around it. But when it comes to maybe internally in the GI system I think in some cases it could be very helpful. Especially in cases in which the microbiome has been altered by treatments. You know, iatrogenic alterations such as antibiotics, surgeries, whatnot
So I think it’s, long as it’s going fine, it’s, for most people the microbiome is something we don’t think about. But when it gets altered in such case like that [00:15:00] or if you have a biofilm. How are we gonna address things like that? Because biofilms can be very hard for us to address.
So I think it’s underrated and overrated. I think in some cases it might be overhyped and that, that really primarily comes from lack of knowledge. If have something we don’t know about, we don’t think, well, eh, it’s just high, you know, it’s overrated. But once we know more about it, we might be saying, hey, this is something that really can help.
So I tend not to be the one who minimizes something at the outset. I tend to wanna know more information before I say that’s not something that’s very helpful. Some cases, things don’t turn out to be helpful. And sometimes they surprise you.
Betsey Zbyszynski: Yeah. And I know there’s several companies out there. Trying to start studying some microbiomes in dermatological conditions, as well as other therapeutic areas. So we’ll see how that comes down the road.
Dr. Todd Schlesinger: Mm-hmm.
Betsey Zbyszynski: How about evaluator assessment training? So training for the evaluator for grading assessments in the protocols. The clinic process.
Dr. Todd Schlesinger: I think that’s something that’s neutral. , I think it’s something that we have to do. There’s inherent bias built into any study. It may or may not just come from the assessment, there’s selection bias. There’s assessment bias. There’s lots of reasons that could be introduced into studies so we have to just work on different ways to make our studies more robust and try to limit that.
So I think that one thing that we don’t utilize enough is blinded evaluators. That could probably help us a lot more because oftentimes the investigator at a site is the same one who’s evaluating the patient outcome, which can introduce bias. You tend to have an upward bias at the beginning. As an outset you wanna make somebody more severe so you can get ’em in the study. Of course you evaluate based on what you see, right? But there’s an inherent and human bias to upscale, upcode a little bit or up evaluate. And then of course you sometimes tend to down evaluate when the patient’s in the study. “Wow, it’s working great!”, you know?
I feel that’s something. I think the use of blinded evaluators, it’s hard because sites may not have independent physicians to do the evaluations. If doing it by photography it can introduce its own biases. So development of maybe onsite raters which is hard for many sites to have a second physician there to do. But that’s something that’s helpful in studies in which you can do it. And we’re seeing more studies that are using centralized review for inclusion, to run subjects by central review before they’re in, as part of the screening process. That can help to reduce bias as well.
So I think evaluator assessment training is something we all do. Of course it’s pretty standardized, everyone has to have it, you have to be trained before it can be delegated. So I feel like that’s sort of a neutral one. It’s something we have to improve on always, as part of our bias reduction plan. But it’s not something new, unless there’s some type of new training that we’re doing it’s something that we just do.
Betsey Zbyszynski: Yeah, coming from the clinical operations side dealing with sponsors, it’s always one of their key questions of, “How are we gonna manage the evaluator training? How are we gonna ensure they’re trained and grading the same throughout the study?”. So it’s always been a topic.
And I think a lot of dermatologists now are very research experienced. The scales are pretty standard for the most part. And over indication so they’re very familiar with the scales.
Dr. Todd Schlesinger: Yeah, there’s a lot of things that come into play there. There’s lighting, you know-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: The standardization of where the patient’s evaluated, there’s lots of things that can affect it. Of course you have skin type, being able to carefully evaluate different skin types and how that might alter the way you interpret assessments. So that’s something that, it’s important to make sure we train on skin of color as well. So, that’s something that’s important.
You know, maybe better training tools. I think we have good training tools now but we probably could do better with it. So that’s something that evolves as we get better educating folks. Its an ongoing process. But I agree that it’s important. And sponsors do focus on it which is what they should be doing.
Betsey Zbyszynski: Mm-hmm. Okay our last topic for overrated/underrated and then we’ll wrap up, is decentralized trials.
Dr. Todd Schlesinger: So I think this means different things to different people, [laughs] you know? What’s the definition of a decentralized trial, right? We kind do that now. We’re not doing trials in one location we do it in multiple sites around, around the country, around the world. I’m not even sure how to define that term. Is it something where there’s more assessments being done at home by subjects? Maybe it’s a home-based type thing where-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: Investigators that go to people’s homes and do assessments. There’s a lot more data being captured electronically with patients, subjects. So I think that’s something, you know? But we already are doing that now just to some extent.
But what does it mean to you? When you think about decentralized trials, what do you think of?
Betsey Zbyszynski: Well typically it would be less office visits. , when we’re asked do we do decentralized trials, are we [00:20:00] involved in any decentralized trials, it’s less office visits. Which I think can be incorporated but for dermatology it can be difficult because the primary endpoint is an investigator grading typically in most dermatology indications. So that needs to be done in person.
We do use electronic patient reported outcomes on a device or on an app. Which I think the patients like having that as part of their participation in a study. So that could be part of decentralized trials too.
Dr. Todd Schlesinger: You know, the other piece of it is real world evidence studies. Which-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: I think this decade, are coming around. And those I think are very helpful because they can give us more data on the use of a medication that we just couldn’t, that you can’t gleam from the registration site. Putting the medication to use in a practice. Doing some assessments and capturing a lot more patient-reported outcomes. And it capturing a lot more of what’s happening in real life as far as what other treatments the patient’s receiving. So instead of excluding that or forbidding other treatments you now wanna see what’s actually being done. How it’s being reduced to practice if you will.
So I think that in that vein, if you wanna call a decentralized trial a real world evidence study it would be considered phase four where maybe it’s done in a larger number of sites. And it could be more in practices that are not trial centers, but they’re a community place for academic practices. And these studies are starting being done in the clinic-
Betsey Zbyszynski: Mm-hmm.
Dr. Todd Schlesinger: Alongside standard of care. I think that can create some very valuable data. In my world, if I were to think about a decentralized trial I would think we’re a real world evidence study.
Betsey Zbyszynski: Yeah that’s interesting, I’m just learning more and more about real world evidence trials. We used to call them in-use studies but now it’s a fancy word-
Dr. Todd Schlesinger: Yeah.
Betsey Zbyszynski: But I think it’s’ a great way to collect data in the market as patients are using them. Well this has been really great to talk to you Dr. Schlesinger.
Dr. Todd Schlesinger: You as well, I enjoyed it! Very helpful.
Betsey Zbyszynski: Yeah. And thanks a lot, have a good afternoon.
Dr. Todd Schlesinger: You as well.
