Vial Presents: Challenges in Hyperhidrosis Trials with Dr. David Pariser

hyperhidrosis trials

Dr. David Pariser, Senior Physician and Principal Investigator at Pariser Dermatology, and Betsey Zbyszynski, VP of Dermatology at Vial, dive deep into the current challenges in hyperhidrosis dermatology trials. Follow Vial on LinkedIn for to stay up-to-date on our latest conversations.

Betsey Zbyszynski: I’m Betsey Zbyszynski. I’m from Vial Health Technology. I’m the Head of Clinical Operations here. And today, we are talking to Dr. David Pariser. We’re gonna talk to him about hyperhidrosis and how it’s being used in the clinical research trials in the industry. How you doing, Dr. Pariser?

Dr. David Pariser: Doing great. Looking forward to this.

Betsey Zbyszynski: Yeah. Do you want to introduce yourself and say a few words first?

Dr. David Pariser: Sure. So I’m David Pariser. I’ve been a practicing dermatologist for 45 plus years in Virginia in a practice that was started by my father in 1946. We had our 75th anniversary just recently. What I’d really do si- since we have a big, large private practice of about 26 providers, I’m- I do clinical trials. I’ve been the principal investigator in over 600 clinical trials in my career including just about everything in there is in dermatology. And today the topic is hyperhidrosis. I was the founding President of the International Hyperhidrosis Society, and have been on the board member since its inception, oh, 15 or 20 years ago. And, really, that’s enough.

Betsey Zbyszynski: That’s great. [laughs] Is th- oh, is that all? [laughs]

Thank you for joining us. We really appreciate having you. have a couple questions to ask you about hyperhidrosis and protocols. The first one is, what are some common pitfalls in hyperhidrosis protocol design?

Dr. David Pariser: Okay hyperhidrosis protocol designs a- all the studies that are b- currently done are predicated a- after the original Botox studies that were done way back in the stone age of the 2000s or maybe 2010-ish. And th- the studies were designed for axillary sweating only. Not sweating on any kind of other body areas. Palms and soles, face an- and scalp under the breasts, groin, any other areas. Just the h- just the axilla.

And the criteria which we used as primary endpoints in- in that study were two. One is a patient reported outcome. And the other is the gravimetric measurement, the actual measurement of sweat production. Now the problem is that because that’s the way that study was done, all sponsors who have devel- developed studies since then have had, have decided that they were just going to follow that path, instead of trying anything new or different, because they knew and they assumed that if they did that, and they met- met their endpoints, that they would get they would get approval. And if they tried to study a, either another type of sweating other than palm, other than the armpits, such as the palm or any other area, or if they tried to use any other kind of endpoints then they would have to, reinvent the wheel. And nobody’s been willing to do that.

And the problem is, that in the world of sweaty patients, hyperhidrosis patients, sure, axillary hyperhidrosis is a problem, but the biggest problem is the hands, sweaty hands and sweaty feet. And people who have palmar hyperhidrosis have the worst quality of life measured by the DLQI evaluation. Worst quality of life than any other diseases that dermatologists treat, including the worst psoriasis, the worst eczema, or anything else you want to talk about. But it’s not something that people are very comfortable with and they’re not very, there’s not very much in the way of treatment for it, until recently.

Last couple of years there has been a flurry of some degree of activity. So the pitfalls in the, in trials are you have to either follow the leader or take your chances. And the problem with, of, following the leader is two things. First of all, the PRO that was used in the Botox studies back in the, in, back in the day, or the HDSS or Hyperhidrosis Disease Severity Scale, is not acceptable anymore by the FDA as an endpoint for registration. The reason for that is because of the way that the questions are asked. They’re asked two part questions, and that’s not s- satisfactory. And also it was never subjected to the rigorous evaluation and that current current one current PROs have to do.

Every sponsor has to develop their own PRO. And that is expensive and time consuming, and, it delays the development process. And that’s a big- big pitfall. And of course once the company developed it, develops it, it’s proprietary and they don’t want to share it with anybody else. and so everybody else has to do their, has to do their own.

The International Hyperhidrosis Society is has a PRO which has not been used in clinical trials yet it’s going to be, and this is one soon which hopefully will become a standard that everybody could use and not have to develop their own every time. So that’s the first problem. Okay now I know [inaudible 00:05:11] you- you asked for the problem. So the second problem is the gravimetric measurement of sweat. Sounds really simple. You should be able to measure the sweat.

How do you measure the sweat? The only way that is described in the literature and considered valid is the underarm sweating. And there’s two ways to do that. One is you take the patient, put them on the table, put the arms up above [00:05:00] the head, take some gauze and tape it to their armpit for- for five minutes. Weigh the gauze before the five minutes and then weigh the gauze afterwards. I’m simp- I’m simplifying, but that’s how you measure how much sweat came out in the last five minutes.

And that’s fine, but it’s extremely variable, because people with hyperhidrosis don’t sweat exactly the same 24/7. And you may get a patient on one particular day that’s sweating a ton. and you may get that same patient who comes b- back the next day and they’re still sweating as much. But, they at that particular moment they’re not sweating much at all. So it makes those values very soft, if you will, very- not very accurate. And you have to have a lot of data to- to to wipe out the noise, of the, of those different …… So- so those are the, in, in high level, and believe it or not that is the high level, not the details there, those are the big pitfalls.

Betsey Zbyszynski: Yeah, that, using using gauze, it sounds archaic. Nowadays there should be a better way to- to measure and realize that people do sweat differently.

Dr. David Pariser: There are lots of other ways but none of those are, have been used in a clinical trial that was done for registration.

 everybody does what the ones were before. I mean there are instruments that can measure the degree of sweating. You know there are other things, but th- that’s, they’re not acceptable. The the- the antiperspirant industry, [inaudible 00:07:00] antiperspirants, measure sweating by putting people in a 105 degree room with- with gauze under their arms. Their arms folded up in there for five minutes, and that’s how they measure sweat, the effect of over-the-counter, cosmetic antiperspirants.

Betsey Zbyszynski: Interesting. Yeah, that’s so challenging to, to start a new study design, or- or introduce a new measurement, or even a new PRO, if it hasn’t been done yet. It’s, there’s a catch-22 there. it’s so expensive for a pharmaceutical company, but yet it’s such a big need. And I’m seeing that in other indications as well.

Dr. David Pariser: We’re hoping that this International- International Hyperhidrosis Society PRO as I said can be i- it’s in a final stages of- of validation and can- can become a standard, which could be used by multiple companies in developing pro- products.

Betsey Zbyszynski: How do you advise sponsors who are concerned about their hyperhidrosis recruitment?

Dr. David Pariser: What I would advise you is talk to somebody who sees a lot of those patients, and, y- and it’s not hard for me. I, you know I’m a been known for this many years and w- we recruited a 120 patient clinical trial by ourselves in six months in the middle of the pandemic.

There, use the standard ways that anybody recruits patients. You do advertising, you, … One interesting thing we tried one time was putting up billboards the highway. Had an interesting response to that. We- we do a lot of TV advertising. Our, we’re not in an expensive TV market. So we do, we have a generic video of sort of doctor things, and we do a voiceover, [inaudible 00:08:48] whatever trial it is. And that’s the way we do it. But there’s no magic way to [inaudible 00:08:52] to- to enroll hyperhidrosis trials [inaudible 00:08:55] any kind of clinical trials, unless you have a stable of- of patients.

Betsey Zbyszynski: And I would think too, with this type of indication some people might- might not even realize that they even have a specific disease called hyperhidrosis. Maybe think they just sweat a lot. Is that true?

Dr. David Pariser: It’s very true. And the- the classic story for [inaudible 00:09:18] hyperhidrosis is the teenager who starts sweating. And, you know m- most axillary hyperhidrosis begins usually around puberty. And so the typical story is the teenager starts sweating, and they go to their parents and say you know, “Mom, dad, I’m sweating like a horse!” And they say, “Oh, come on, you’re just normal, everybody starts to sweat. It’s part of your- your adolescence.” They may even go to their pediatrician who blows them off like that.

And, but then they realize that they’re smearing their schoolwork and they’re their hands are dripping and shorting out their keyboard and their computer. And- and that’s- that’s you know that’s just one of the many things that can happen. Palmar hidrosis actually starts at a younger age. Often in elementary school aged children, or even earlier.

Betsey Zbyszynski: Wow.

Dr. David Pariser: And sometimes people [inaudible 00:10:06] realize that their kid has hyperhidrosis when it’s the first day of kindergarten and mom or dad is taking the child and holding hands, and the hand is really sweaty. “Wow, what is this?” so- but, there are some people just sweat a lot. And there’s no real line to draw. When- where does heavy sweating end and hyperhidrosis start? There are some specific clinical diagnostic criteria. But, you know somebody who is sweating a ton may, who may not have the- the specific diagnostic criteria, still deserves some kind of treatment.

Betsey Zbyszynski: Yeah, it’s sad. I’m sure for a lot of people it’s frustrating out there, not- not really knowing why it’s happening to them, maybe because they’re stressed. They might think it’s something like that, and not something internal. 

Dr. David Pariser: They do. And what happens is, they go online and there’s there’s some very good information, and there’s some very poor information online. the best place to go online to get information on hyperhidrosis is the International Hyperhidrosis Society website, sweathelp.org. Sweathelp.org and if somebody spends half an hour on that website, they will know more about sweating than most doctors do.

Betsey Zbyszynski: [00:10:00] Great, thank you for saying that, sweathelp.org. What is the most exciting development in hyperhidrosis that you did not expect?

Dr. David Pariser: I- I get involved in development of protocols in- in an early stage, so there’s not, nothing much gets sprung on me. Oh, there was a- a, the newest thing just approved a couple weeks ago was a orally disintegrating tablet of glycopyrrolate. it’s called Dartisla. Glycopyrrolate has been used a long time. It’s an oral agent off-label, of course, because it’s not a FDA-approved. In fact nothing, no systemic agent is FDA-approved for treatment of sweating. But this medication is is one which glycopyrrolate [inaudible 00:12:12] for years. The orally [inaudible 00:12:13] disintegrating tablet does have some advantages over the old over the old tablets. And we’re actually- we’re starting a clinical trial with the new one to see how it’s going to work.

Betsey Zbyszynski: What about devices? Have you ever used any devices outside of injectables?

Dr. David Pariser: Yes, there’s, there are several devices. The- the one that’s in most common use right now is microwave thermolysis called MiraDry, which is a procedure that’s used for underarm axillary hyperhidrosis only. And it’s a device that basically fries the sweat glands with microwaves in a very controlled way, c- cooling the surface of the skin, so it doesn’t burn the skin, but it literally, permanently eradicates the sweat glands. That’s only for use in the underarms.

There’s another device called iontophoresis that’s been around for years, probably decades, which is used to treat palms and soles. Iontophoresis is used for other things in medicine, but, by putting your hands and feet in these trays of water, plain water out of the sink and passing a specific kind of electric current through the water that is very helpful for palmar and plantar, palms and soles, hyperhidrosis, if you keep it up. But you got to do it couple times a week.

Betsey Zbyszynski: So basically everything’s just a treatment, nothing’s permanent?

Dr. David Pariser: The MiraDry, the microwave thermolysis is permanent. There are some other, there are some other treatments. There ultrasound has been used. Lasers have been used. Anything that destroys the sweat glands, theoretically from the underarms or anywhere actually would be helpful. There are some, some local surgical procedures excising the sweat glands, but those are not done much anymore, because of the better medical treatments that we have.

Betsey Zbyszynski: So the year is 2027. What is everyone talking about in hyperhidrosis?

Dr. David Pariser: Everybody’s talking about how we still need something better for hands and feet. I- I really hope that’s going to be forthcoming. And really, for hands and feet, probably it’s going to be systemic treatment. There’s at least one systemic drug in the pipeline that’s probably two, three years at least from- from coming out, which may be very helpful. For the, hopefully somebody will do clinical trials on- on some of the older agents that we have, but really there’s no incentive for anybody to do that, because they’re all generic.

Maybe- maybe there will be some better devices to ablate the- the microwaves. Maybe some more specific lasers, maybe the microwave thermolysis can be refined a bit.

Betsey Zbyszynski: And biologics aren’t in this realm, is that correct?

Dr. David Pariser: That is correct. There’s really no reason why a biologic should be effective or could be effective in- in hyperhidrosis. We- we save those for psoriasis and atopic dermatitis for now. but there will be are many other indications [inaudible 00:15:16] be useful for as well.

Betsey Zbyszynski: Yeah. On a scale of 1 to 10, how optimistic are you about the current therapeutics in clinical trials for hyperhidrosis?

Dr. David Pariser: I’m- I’m optimistic about what is currently in clinical trials, is that the question?

Betsey Zbyszynski: Current, yeah.

Dr. David Pariser: The development program for at least one of the of the agents that I’m aware of was stopped, which I’m not sure why. There’s not a very robust active pipeline right now. There’s one that I mentioned that- that’s on hold, but will come back for, two- two or three years from now. It’s pretty good.

I- I’m- I’m hoping that what we’ll be able to do is to get the indication expanded to palms and soles, because not having that in- indication is often a reason why insurance companies will deny [inaudible 00:16:16] cut and deny coverage. So my hope is that the FDA will realize that this is really, hyperhidrosis is really a quality of life thing, more than it is a medical, I mean it’s a medical disease, more than it is a physiological problem. Nobody dies of hyperhidrosis. But you certainly can, affect your employment, your social relations, your- your friendships your- your daily life. And- and so what I would hope would be, that the FDA would eventually say, “Okay, the heck with all this gravimetric measurement. Let’s use a PRO only and see what we get.”

The- the study that I mentioned that we did 120 patients in- in six months in my site alone, was a PRO study only. Now, it’s not going to get anybody a label change, but it’s going to get some good information on uses of this particular product on the palms, which is what- what we studied.

Betsey Zbyszynski: Yeah, I think [00:15:00] across the board in a lot of dermatology indications, PROs are being used more and more. I mean I’ve been in dermatology, almost 20 years now, and initially we didn’t h- use the quality of life forms. And now, more and more, it is being incorporated into protocols. I think people are realizing that these aren’t necessarily life-threatening diseases, but the quality of life of these people is- is very compromised.

Dr. David Pariser: I- I agree with you completely. The problem is that the FDA doesn’t agree with you or us, or anybody about this. And although, you’re absolutely right, is that most sponsors are- are using quality of life measures in their in their protocols, it doesn’t make it to the label. It doesn’t make it to the packaging, to the prescribing information package insert. The FDA doesn’t they probably look at it, but they don’t view that as a metric that is acceptable for registration. So that- that’s, that ends up being something that gets gets a publication or a poster or both, and- and gets, presented from podiums and lectures but doesn’t [inaudible 00:18:32]-

 … doesn’t make it to promotional promotional setting. Which you have to be on the label to do it, of course.

Betsey Zbyszynski: Yeah, that’s- that’s too bad. Especially, I know with psoriasis the suicide rate is high. I’m sure it’s something like that in hyperhidrosis too, with people with severe. 

Dr. David Pariser: We don’t really know that statistic because nobody has ever done a study that’s asked for it.

 We certainly, the Hyperhidrosis Society gets emails every week from people with hyperhidrosis who are contemplating suicide now, if they completed the suicide, they wouldn’t be sending emails. But so it- it’s- it’s a significant psychological issue, for sure.

Betsey Zbyszynski: If you had 250 million dollars, and could allocate it into a therapeutic development, where would you put it?

Dr. David Pariser: For hyperhidrosis, or for anything, you’re asking me? For hyp-

Betsey Zbyszynski: For anything.

Dr. David Pariser: For anything? Okay, we’re talking now, I’m- I’m going to skip out of hyperhidrosis and go to to psoriasis. Now you might think that there’s not a whole lot of need for treatment for psoriasis. We have 11 biologics for psoriasis. We have some JAK inhibitors that are currently in clinical trials. We have other agents that are oral, small molecule, and other biologics, in the treatment of it. Why, so why do I want to spend my 250 million dollars on that?

Here’s what I want to do. And this could, this is applicable to atopic dermatitis too, but more so psoriasis. Some people who have psoriasis, really bad psoriasis, it goes away by itself. Why? Something happens that interrupts that inflammatory cascade, and the psoriasis goes away. It may stay away for a long time, it may come right back, but it does go away. What if we could have a drug that would somehow do whatever it is the body’s doing, and shut it off and cure psoriasis? Okay? You know maybe it’s just one of the biologics we have in some kind of megadose. Maybe it’s something new. But that’s my moonshot for n- number one moonshot. I have other shots that are going just into suborbital space, but that’s my biggest one.

Betsey Zbyszynski: Yeah. People wouldn’t have to keep coming back, I know the biologics work, which is great, but that’s forever, if they’re coming once a month, because they don’t want to go off it in fear that their psoriasis will come back.

Dr. David Pariser: That’s true. That’s the worst fear that people have with psoriasis. I had patient on one of the psoriasis clinical trials one time. It was one of the long-term trials, and the patient had been completely clear, 100% clear, for two years. And the guy came in one time and said, “Doc, the stuff isn’t working anymore.”

“What do you mean it’s not working?”

“I’ve got a spot the size of a quarter on my knee.”

I said, “What are you telling me? Do you remember when you used to have more than half your body with this on it? What are you talking about it isn’t working anymore?” and then I always tell him we always want you to have a little bit of the psoriasis, that way we know we’re not giving you too much medicine.”

But he- he wasn’t too happy [inaudible 00:21:47]

Betsey Zbyszynski: I know. Thank you so-

Dr. David Pariser: That’s the fear. [inaudible 00:21:52]

Betsey Zbyszynski: Yeah.

Dr. David Pariser: The fear is, when is it going to come back?

Betsey Zbyszynski: Of course. Oh my gosh, of course. And I guess if they see just a little bit, to them, it’s it’s all your perception. 

Dr. David Pariser: That’s going to, that little bit, and then what’s it going to be? Am- am I going to go back to that awful stage I used to be? [inaudible 00:22:08]

Betsey Zbyszynski: Thank you so much, Dr. Pariser. This has been a pleasure. I’ve certainly learned a lot more about hyperhidrosis and the current market, and I do hope that some of these studies and protocols that you’re working on will make it to the market, and will be successful.

Dr. David Pariser: That’s what we do. I- I used to say when a treat- because the hyperhidrosis patient has the worst quality of life of anything. And when you treat them depending on, this- this was a study that was done when you treat them with Botox, their DLQI, the change in their DLQI is greater than the change in the DLQI of anything else we do. Now, I can’t say that anymore because the biologic for psoriasis also now do that much. But it used to be, and s- and still is, a great improvement in people’s quality of life.

Betsey Zbyszynski: Yeah. [00:20:00] Yeah. Thank you again for joining us. We really appreciate it.

Dr. David Pariser: Okay. All right. Thank you very much.