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The Future of Acne Treatment · The Science of Skin

• 0:00
  SPEAKER_00: This episode of the Science of Skin Podcast is sponsored by Galderma.
• 0:12
  SPEAKER_01: Hello and welcome to the Science of Skin Podcast.
• 0:15
  SPEAKER_01: My name is Dr.
• 0:15
  SPEAKER_01: Ted Lane.
• 0:16
  SPEAKER_01: I'm a board-certified dermatologist and your host for today.
• 0:20
  SPEAKER_01: I am joined by a very esteemed colleague, Dr.
• 0:23
  SPEAKER_01: Andrew Alexis.
• 0:25
  SPEAKER_01: Dr.
• 0:25
  SPEAKER_01: Alexis is a professor of clinical dermatology at the Weill Cornell Medicine.
• 0:31
  SPEAKER_01: He's also past president of the Skin of Color Society.
• 0:35
  SPEAKER_01: Today we are going to chat about triferitine cream.
• 0:40
  SPEAKER_01: The brand name is Accleaf.
• 0:42
  SPEAKER_01: It is a novel or new retinoid or type of retin A cream that has been around, Andrew, for gosh, how long now?
• 0:51
  SPEAKER_01: I can't even remember when it was first launched.
• 0:53
  SPEAKER_02: You know, it's a great question.
• 0:54
  SPEAKER_01: I lose track of time, but it's been a few years now.
• 0:57
  SPEAKER_01: It's been a few years now, yeah.
• 0:59
  SPEAKER_01: And really the wonderful thing about Ackleaf is that there's been continued development and investigation about this new molecule.
• 1:08
  SPEAKER_01: So we really understand how it works in the skin and some of the kind of interesting attributes of triferitine compared to its peers.
• 1:18
  SPEAKER_01: Would you would you agree with that?
• 1:19
  SPEAKER_02: I would.
• 1:20
  SPEAKER_02: And you know, we like to refer to triferitine as the fourth generation uh topical retinoid.
• 1:26
  SPEAKER_02: And uh uh so it's it's it's wonderful to see an advance in this uh category of uh of agents that we depend on so so heavily when when managing acne patients.
• 1:39
  SPEAKER_02: And so when we think of the original retinoid of tretinoin, and then the development of uh of adapylene and tazerotine, here we have our fourth generation uh uh retinoid molecule, treferitine.
• 1:52
  SPEAKER_01: It sure is an interesting molecule.
• 1:54
  SPEAKER_01: Remember that tretinoin was all tra or is all transretinoic acid, right?
• 1:59
  SPEAKER_01: So it is a it is a a molecule that binds to all the retinoic acid receptor subtypes.
• 2:06
  SPEAKER_01: So there are three receptor subtypes in all of our cells that tretinoin would bind to.
• 2:12
  SPEAKER_01: But but a cleaf or triferitine is different.
• 2:15
  SPEAKER_01: Uh Andrew, tell tell us how it's a little bit different.
• 2:18
  SPEAKER_02: Yeah, indeed.
• 2:19
  SPEAKER_02: So so cleaf binds to um, preferentially to the RAR gamma um receptor.
• 2:26
  SPEAKER_02: So it's an RAR gamma um uh agonist.
• 2:30
  SPEAKER_02: And it turns out that RAR gamma is uh is the predominant uh receptor subtype uh uh uh in the skin.
• 2:40
  SPEAKER_02: So uh this is highly selective for RAR gamma.
• 2:44
  SPEAKER_01: We know that retinoids, pretty much all of them now, we know that they do amazing things for the skin.
• 2:49
  SPEAKER_01: We we use them a ton in acne because they have such beneficial effects on helping the skin cells turn over more quickly, and by accelerating the cell cycle, we're able to stop the cells from getting caught in the hair follicles, leading to what we call microcomodones or microscopic blackheads, which can then develop into the acne blemish of the pimple or the pustule that we're we commonly see with inflammatory acne.
• 3:18
  SPEAKER_01: But then triferritene, again, through advanced investigation, does a lot more than that.
• 3:24
  SPEAKER_01: And and there's some pretty interesting genetic data, Dr.
• 3:27
  SPEAKER_01: Alexis, that I think we should just kind of do a quick overview of.
• 3:31
  SPEAKER_02: Yeah, so it's it's interesting.
• 3:33
  SPEAKER_02: This molecule, uh, the more and more we learn about it, it's it's it's it becomes more fascinating.
• 3:39
  SPEAKER_02: Uh this there was a recent uh gene expression uh study that you that you mentioned, Ted, um, that uh that uh showed that uh um that there's activation of retinoid modulated processes, including epidermal differentiation, proliferation, stress response, um uh proteolysis, cell adhesion, so a number of different effects.
• 4:05
  SPEAKER_02: And uh we some of this some of these uh identified um differences in gene expression might help to explain some of the clinical outcomes that we've observed with triferritin, including improvements in scarring and post-inflammatory hyperpigmentation.
• 4:24
  SPEAKER_02: So one of the um unique attributes or but distinct attributes of triferritin is in addition to the traditional um comatolytic effects of retinoids, it does have some potent um uh depigmenting, if you will, or reduction of excess pigmentation effects, as well as some effect on um uh scarring, uh reducing atrophic scars.
• 4:49
  SPEAKER_02: And I know we'll be talking about some clinical studies that support that too.
• 4:53
  SPEAKER_01: Yeah, you uh you know, you mentioned the scarring and some of the genetic data that's been been developed.
• 4:58
  SPEAKER_01: I mean, they showed uh what I think 67 unique genes were affected by triferitin, uh, and these genes were related to the migration of cells, um, uh inflammatory response, and extracellular matrix remodeling.
• 5:12
  SPEAKER_01: But then really interesting the way that triferritin affected macrophages, you know, there's there's two types of macrophages, just broadly, there's the M1 and M2 macrophages.
• 5:22
  SPEAKER_01: The M1 tend to be pro-inflammatory, M2 anti-inflammatory, but there's an actual subtype of the M2 macrophages.
• 5:30
  SPEAKER_01: I feel so smart now talking about all this.
• 5:32
  SPEAKER_01: It's called the SPP1 population.
• 5:36
  SPEAKER_01: And uh that one, although it is part of the anti-inflammatory macrophage family, it is responsible for fibrosis.
• 5:44
  SPEAKER_01: And we think that by targeting and downregulating these SPP1 type M2 macrophages, we're able to possibly decrease the scarring.
• 5:54
  SPEAKER_01: And so maybe that's the pull through from what we see in some of the studies that we're about to talk about.
• 5:59
  SPEAKER_01: Uh, kind of we're showing bench top in vitro data that can actually be associated with phenotypic clinical data, which we always love to see.
• 6:09
  SPEAKER_01: Uh, and that's kind of the the investigation I was talking about that that Galderma has really done with this molecule.
• 6:15
  SPEAKER_01: But but Andrew, let's just do kind of a quick overview of the phase three registration program, where it was essentially triferritin versus vehicle, wasn't it?
• 6:26
  SPEAKER_02: Indeed, for the phase three um uh trials, triferitine versus vehicle.
• 6:31
  SPEAKER_02: And yeah, I just want to reiterate the the uh the exciting gene expression data that you mentioned, and as you said, 67 genes that uh primarily involved in cellular migration, inflammation, and extracellular matrix reorganization.
• 6:47
  SPEAKER_02: Um and uh those specific macrophages that you mentioned, SPP1 uh uh positive macrophages, are uh, as you pointed out, a subset of more proliferative macrophages that uh are found in fibrotic tissue.
• 7:05
  SPEAKER_02: And so there is that link between what uh we have come to observe clinically with respect to uh effects on scarring.
• 7:14
  SPEAKER_02: But uh back to the phase three data, yeah, compared to vehicle, um uh triferitine compared to vehicle demonstrated significant uh efficacy with respect to inflammatory lesions, non-inflammatory lesions, uh, investigator global assessment of uh of acne severity.
• 7:30
  SPEAKER_02: But something that makes it quite unique uh in the retinoid class is that not only was it studied for acne involving the face, but also truncal involvement.
• 7:42
  SPEAKER_02: So um efficacy was demonstrated uh in for both uh trunchal acne and facial acne, which is particularly exciting.
• 7:50
  SPEAKER_01: Yeah, I I really love the fact that they investigated on both, and essentially the same efficacy that we saw on the face, we saw on the trunk, which was surprising to me because I I often consider the acne on the trunk as a little bit more difficult to treat.
• 8:04
  SPEAKER_01: The the trunk doesn't absorb topicals as well.
• 8:08
  SPEAKER_01: It's a little bit more difficult to penetrate.
• 8:10
  SPEAKER_01: The hair follicles are more spread out, which is where the acne blemishes arise.
• 8:14
  SPEAKER_01: And so, you know, we may need more uh medication in order to achieve the benefit just because the target is spread.
• 8:22
  SPEAKER_01: Uh, but indeed, the results were exactly the same in terms of reduction of inflammatory and non-inflammatory lesions, which which was surprising, but great because it allows us to use monotherapy for these patients.
• 8:34
  SPEAKER_01: Exactly.
• 8:35
  SPEAKER_01: Yeah.
• 8:36
  SPEAKER_01: Um, you know, I think before before at Cleve, sorry to interrupt, before triferitine, we were kind of using one retinoid for the face and then maybe some other products for the body.
• 8:45
  SPEAKER_01: I don't know if this changed your clinical um regimen at all.
• 8:49
  SPEAKER_02: Yeah, absolutely.
• 8:50
  SPEAKER_02: Uh to your point, Ted, you know, before before triferritin, we didn't have uh um such robust data for uh frankly any therapy for trunchoacne, to my knowledge.
• 9:03
  SPEAKER_02: So uh the ability to use uh a retinoid no less uh for trunchal acne and get this kind of efficacy has yes, has definitely changed my practice.
• 9:14
  SPEAKER_01: You know, and then they didn't stop there, right?
• 9:16
  SPEAKER_01: As I mentioned, we've learned so much more about how triferritin can affect the entire acne journey.
• 9:24
  SPEAKER_01: Uh, because I'm not sure that as dermatologists, we should consider our job done once the acne lesions have stopped arising or have been eradicated.
• 9:36
  SPEAKER_01: You know, I I think there's more for us to do.
• 9:38
  SPEAKER_01: I'd I'd love to get your view on that.
• 9:41
  SPEAKER_02: Yeah, and I think what you're alluding to, Ted, is that you know, in addition to the papules, the pustules, the comodones, the actual lesions of of uh of acne that our patients come to us presenting with clinically, there's a whole other dimension to it, right?
• 10:01
  SPEAKER_02: Uh there are the sequelae of post-inflammatory hyperpigmentation, which can have uh as much of an impact on patients and sometimes even more of an impact on patients than the primary uh inflammatory or non-inflammatory lesions, um uh acne scarring, uh, and then the psychosocial uh impact of having acne.
• 10:24
  SPEAKER_02: And so we have all of these other dimensions beyond just uh narrowly focusing on lesion counts.
• 10:35
  SPEAKER_00: This episode of the Science of Skin Podcast is sponsored by Galderma.
• 10:42
  SPEAKER_01: You mentioned the psychosocial aspect of acne.
• 10:45
  SPEAKER_01: It's it's something I think about pretty much every time I see a teenager with acne because we know from earlier data, again, data that is largely generated by Calderma, um, that when a teenager develops acne and and the effect it has on their self-esteem, it it's not like once you clear the acne, the self-esteem will immediately rebound.
• 11:05
  SPEAKER_01: Uh, unfortunately, we know from this data that the the effect on confidence and self-esteem actually persists throughout adulthood as well.
• 11:14
  SPEAKER_01: Um, so that I always think about that because when I when I have a teenager with significant acne, I think about how it's affecting them psychosocially and now and in the future, and how boy, that that puts a huge onus on us to get them better quickly because the last thing we want is for them to be dealing with the the psychological aspect of acne 10 to 20 years later.
• 11:38
  SPEAKER_02: Yeah, well said.
• 11:40
  SPEAKER_02: And and you know, with that in mind, I think it's uh it's helpful for us as clinicians when we take care of our acne patients, particularly in the initial consultation, but really throughout the acne journey, to take one extra moment and and uh uh ask our patients, assess how how the acne might be affecting them uh in their uh social lives, professional lives, their overall self-esteem.
• 12:08
  SPEAKER_02: And we can glean a lot of that, even if it's not said verbally.
• 12:12
  SPEAKER_02: There are also many nonverbal cues, aren't they?
• 12:14
  SPEAKER_02: Aren't there?
• 12:15
  SPEAKER_02: We can we can we can uh we can see when we walk into the into the room.
• 12:19
  SPEAKER_01: Yeah.
• 12:20
  SPEAKER_01: It's tough to be a teenager in any way.
• 12:23
  SPEAKER_01: And then you add significant acne and it just makes that journey even more difficult.
• 12:28
  SPEAKER_01: Uh I I was lucky as a teenager, I didn't, I just didn't experience a lot of acne, but I remember my friends that did, and what a struggle.
• 12:37
  SPEAKER_02: Yeah, not to overshare and get too personal, but I'll just in in response to that context, I I can say that I I certainly suffered from acne throughout uh my teenage years and even uh through my uh early 20s and uh was uh treated during medical school too.
• 12:53
  SPEAKER_01: So well let's uh let's jump into to kind of I'd love to actually get your thoughts on how you best utilize triferitine in in your just daily practice and where do you find it slotting in and and and it's being the most successful for you because I think that kind of takeaway will be huge for audience as well.
• 13:13
  SPEAKER_02: Yeah, so um first of all, taking a step back, I I still I view retinoids as really the foundation of our uh approach to treating acne.
• 13:22
  SPEAKER_02: And so the ability to use an advanced retinoid, um, this fourth generation retinoid with um RAR gamma um selectivity with facial and trunk data and some other data that we're going to talk about, um, it's really become uh one of my my go-to retinoids when when it when it's accessible for my patient.
• 13:46
  SPEAKER_02: Um so I'll frequently use um uh triferitine, have my patients use triferritine at night, um, and uh whether it's on the face or face and trunk, depending on their involvement.
• 14:00
  SPEAKER_02: And then for the morning, even though the clinical trials demonstrated monotherapy, uh demonstrated efficacy with monotherapy.
• 14:06
  SPEAKER_02: In the real world, of course, we we we will combine uh multiple agents to try to target multiple uh etiologic factors, uh pathogenic factors for acne and increase the overall efficacy.
• 14:20
  SPEAKER_02: So I I might have the patient use a um a benzol peroxide clindamycin formulation in the morning coupled with the retinoid at night.
• 14:30
  SPEAKER_02: They might use a topical azoleic acid formulation if their sensitivity to benzy peroxide or if there's a sort of urgency to work harder on the hyperpigmentation front and having uh two agents working on hyperpigmentation at the same time, the retinoid and azoleic acid.
• 14:48
  SPEAKER_02: These would be some examples.
• 14:50
  SPEAKER_02: Or the uh glascoderone, uh, are another one of our newer agents, and in this case, uh targeting the uh um the sebaceous gland and uh uh inhibiting an androgen receptor there.
• 15:04
  SPEAKER_02: Um that's a also a potential combination of uretinoid at night and glascodorone in the morning.
• 15:10
  SPEAKER_02: So there's there are many different uh combinations that one can consider on a case-by-case basis depending on the uh the clinical severity, the type, the predominant types of lesions.
• 15:20
  SPEAKER_02: And this is not to exclude oral therapies.
• 15:23
  SPEAKER_02: There are scenarios where patients will have more severe uh acne and will combine the topical uh regimen, including triferritin, with an oral uh agent like doxycycline.
• 15:36
  SPEAKER_01: Wow, it sounds like it's really a foundational, like you said, it's variations on a theme, but that theme is triferritin for a lot of your patients.
• 15:43
  SPEAKER_01: Indeed.
• 15:44
  SPEAKER_01: Yeah.
• 15:45
  SPEAKER_01: I I have to agree.
• 15:46
  SPEAKER_01: I think retinoids play such an important role in acne.
• 15:50
  SPEAKER_01: And the more and more we learn, as we're gonna discuss now, the more important they are.
• 15:55
  SPEAKER_01: And you know, in addition to that, the the beneficial aesthetic effects of of triferritine cannot be understated.
• 16:02
  SPEAKER_01: I I use it, I don't have acne, but I use triferritin every night because I think it has amazing benefits just aesthetically to improve collagen production and decrease pore size.
• 16:13
  SPEAKER_01: Um, so I I I like it for the other benefits in addition to its acne fighting benefits.
• 16:20
  SPEAKER_01: But let's go into those phase four studies.
• 16:23
  SPEAKER_01: I mean, I think we've danced around them.
• 16:24
  SPEAKER_01: It's probably time for us to actually talk about them.
• 16:27
  SPEAKER_01: Um, there is a phase four study called the START trial, which really looked at at acne scarring.
• 16:33
  SPEAKER_01: And I think, you know, in preparation for this trial, and and they Galderma had had performed a trial much like this with previous um uh generations of products uh targeted at acne, and they found that not all acne scars, you know, usually we think of a scar as being something permanent, but indeed they showed that through some really interesting data that not all scars are permanent, are they?
• 16:57
  SPEAKER_02: Exactly.
• 16:58
  SPEAKER_02: I I think that, and as you pointed out, there were some previous uh Galderma-sponsored studies with uh earlier generation product that first set the stage for understanding, having a better understanding of the role of topical retinoid uh therapy in uh atrophic acne scars.
• 17:17
  SPEAKER_02: It's it's it's actually remarkable to look at that data and see that we can rever we can reduce the number of atrophic uh acne scar lesions with with retinoid therapy.
• 17:28
  SPEAKER_02: And specifically with with a cleaf, this phase four study with a cleaf was a split face design uh where uh uh half the face is randomized to triferitine cream treatment uh uh once daily, and the other side uh with vehicle.
• 17:46
  SPEAKER_02: And um and the number of atrophic scars uh were uh were assessed at various time points uh over the course of 24 weeks.
• 17:57
  SPEAKER_02: Um and in order to qualify for the study, of course, in order to do a split face, these are patients who have symmetrical uh involvement of uh of atrophic scars uh caused by acne.
• 18:10
  SPEAKER_02: Um and patients had to have at least 10 atrophic acne scars to qualify.
• 18:17
  SPEAKER_02: And so when when looking at the efficacy for this, uh what was demonstrated was statistically significant reductions in uh not just the acne, but also in the atrophic acne scar count uh over the course of uh 24 weeks.
• 18:34
  SPEAKER_02: So at week 24, there were significantly greater uh reductions in the from baseline uh in the triferritin side versus the vehicle treated side.
• 18:44
  SPEAKER_01: Yeah, it's interesting.
• 18:46
  SPEAKER_01: Even prior to this data, they showed that uh about a third of scars are actually transient.
• 18:51
  SPEAKER_01: So not all scars are going to stick around forever.
• 18:54
  SPEAKER_01: But then they also looked at uh which type of lesion leads to an acne scar.
• 19:01
  SPEAKER_01: And it's the post-inflammatory lesions that are that predominantly cause acne scarring.
• 19:07
  SPEAKER_01: So, for example, those post-acne PIE, the post-inflammatory erythema, for example, that we we look at those, those kind of red marks on the skin that are the remnants from the papillar pustule, those are the ones that tend to form eight out of ten scars are derived from PIE.
• 19:25
  SPEAKER_01: So, so I don't, that's what we we were talking about earlier, right, Andrew?
• 19:29
  SPEAKER_01: Like, is our job done when we get to the PIE?
• 19:32
  SPEAKER_01: Um, I think we probably are not done at that point because we know if my goodness, eight out of ten scars derived are derived from PIE, it it we we need to keep going with treatment in order to hopefully prevent that, right?
• 19:48
  SPEAKER_01: And I think triferritin fits right in there.
• 19:51
  SPEAKER_02: Absolutely.
• 19:52
  SPEAKER_02: And you know, I'm so glad you brought this up because it it now brings to our attention the fact that we're probably using these terms as they're probably misnomers.
• 20:03
  SPEAKER_02: We say post-inflammatory hyperpigmentation, post-inflammatory erythema, and and I think uh increasingly we recognize that these are actually misnomers, and there really is sub-clinical inflammation uh uh in these in these areas.
• 20:20
  SPEAKER_02: Um of course with PIE, you see the inflammation, as you can see the persistent erythema, but in the context of post-inflammatory hyperpigmentation, the eye might only pick up what appears to be uh increased pigmentation, but subclinically there's there is histologic evidence of inflammation.
• 20:37
  SPEAKER_02: An old study by Robot Halder uh years ago demonstrated that.
• 20:41
  SPEAKER_02: Uh and uh and knowing the scar data, it makes sense that these very lesions would be the ones that would have a high risk of developing atrophic scars.
• 20:53
  SPEAKER_01: Yeah, and and just to kind of quantify the scar reduction, if we look at that, that side of the face on average had about a 51% reduction from baseline in terms of the number of scars at week 24 versus 23% on the vehicle side.
• 21:08
  SPEAKER_01: So we certainly see a very large difference between the active versus the vehicle side.
• 21:13
  SPEAKER_01: And, you know, what's interesting also is that this is some of the first data where we've seen week 24 data in terms of acneaf efficacy or triferritene efficacy, just in inflammatory acne and IgA success.
• 21:26
  SPEAKER_01: And we from, you know, if we looked at this data, week 12, we had about a 58% reduction in the total lesion count, going down to 70% reduction at week 24.
• 21:36
  SPEAKER_01: So we don't seem to plateau with this drug either, uh, in terms of its efficacy.
• 21:42
  SPEAKER_01: And that I love to, now that we have that week 24 data, I talk about that all the time with patients.
• 21:46
  SPEAKER_01: I don't know if you if if that has has helped you with your discussions.
• 21:50
  SPEAKER_01: Yeah, absolutely.
• 21:52
  SPEAKER_01: You know, it's just it's great to have the data showing continued improvement over time because we know with acne, what it's not.
• 22:00
  SPEAKER_01: A sprint, right?
• 22:00
  SPEAKER_01: It's a marathon.
• 22:01
  SPEAKER_01: We're not curing, we're controlling.
• 22:03
  SPEAKER_01: And uh, and that we can do with with triferitine as shown with that data, and deal with some of the sequelae, such as the scarring.
• 22:12
  SPEAKER_01: Now, now that that is the start study.
• 22:16
  SPEAKER_01: Andrew, the other study, it's called the LEAP study.
• 22:19
  SPEAKER_01: And I think that one's the one that we probably should spend even more time on because that one's associated or focused on the post-inflammatory or acne-induced hyperpigmentation, as you said, misnomered.
• 22:32
  SPEAKER_02: Yes, yes.
• 22:33
  SPEAKER_02: Uh, that terminology is very intentional.
• 22:36
  SPEAKER_02: Um, acne-induced hyperpigmentation or AIH.
• 22:41
  SPEAKER_02: Um, and you know, when when working with this study, we thought carefully of the terminology, and that that's that's not an accident.
• 22:50
  SPEAKER_02: That's acne-induced hyperpigmentation instead of post-inflammatory hyperpigmentation.
• 22:54
  SPEAKER_02: So glad you you called that out.
• 22:57
  SPEAKER_02: So um, so the LEAP study that you mentioned, Ted, yes, it was a um uh a phase four study uh of uh triferritin for act to assess its uh efficacy in acne-induced post-inflammatory hyperpigmentation.
• 23:14
  SPEAKER_02: And you know, we've we have data from in terms of retinoids and hyperpigmentation, we have data dating back all the way to the uh early to mid-90s with with tretinoin demonstrating that tretinoin could improve acne-induced hyperpigmentation.
• 23:30
  SPEAKER_02: But it did so with pretty a pretty high rate of of uh irritation uh in those days.
• 23:36
  SPEAKER_02: And uh since then we've seen some small studies with uh with uh tazerotine, um, some observations of improvement with adaplene, but no formal big robust studies that are vehicle controlled uh uh for acne-induced hyperpigmentation until uh with triferritin.
• 23:57
  SPEAKER_02: So this really builds on our overall body of data for using uh retinoids for hyperpigmentation.
• 24:04
  SPEAKER_02: So um this this study was a six-month study or 24-week study, and uh patients were randomized to either triferritin cream uh plus a skincare regimen that included uh gentle cleanser and a moisturizer containing sunscreen, versus a uh uh the group that got vehicle as well as a moisturizer with containing sunscreen and a gentle cleanser.
• 24:29
  SPEAKER_02: And uh it turns out over the course of the 24 weeks, both groups did show reductions in post in hyperpigmentation, uh, but there was a significantly greater um reduction in at least the secondary endpoint called poppy score, PAHPI, which is post-acne hyperpigmentation index, which takes into account lesion number, size, uh uh, and extent.
• 24:57
  SPEAKER_02: And uh with that uh particular secondary endpoint, there was a significantly greater improvement at week 24.
• 25:05
  SPEAKER_02: The primary endpoint actually was a more sort of general overall uh assessment of hyperpigmentation severity called ODS, which stands for overall disease severity.
• 25:16
  SPEAKER_02: It's and uh in that particular using that particular outcome measure at week 24 was actually a non-significant difference.
• 25:23
  SPEAKER_02: Uh but at earlier time points uh there there was uh um significantly greater uh improvement in hyperpigmentation in the triferritin group uh versus the vehicle.
• 25:35
  SPEAKER_02: So I know that's a very uh long and somewhat complicated answer, but the bottom line is that there were the primary efficacy endpoint chosen in the study was a more of a general uh measure of hyperpigmentation called ODS.
• 25:49
  SPEAKER_02: And at that six-month time point of week 24, which was the primary endpoint, it was a non-uh significant uh difference.
• 25:58
  SPEAKER_02: But using the the secondary endpoint uh of PHPI, a validated uh in uh and uh tool to measure acne-induced hyperpigmentation severity, there was significant uh uh lead greater improvement in triferitine.
• 26:14
  SPEAKER_02: So uh your thoughts, Ted?
• 26:17
  SPEAKER_01: Yeah, you know, I think it's such an interesting study.
• 26:19
  SPEAKER_01: And um, you know, I think the ODS was a relatively new scale uh when when this study was started.
• 26:27
  SPEAKER_01: And so there, I think there was some a lot of discussion, and I'm sure you were involved in that, Dr.
• 26:31
  SPEAKER_01: Alexis, in regards to which is our primary endpoint.
• 26:34
  SPEAKER_01: And it turned out that the ODS probably wasn't the right scale necessarily to use as primary, just because with good sun protection, we saw that that the vehicle, you know, those on the vehicle plus sun exposure, sun protection, I should say, caught up eventually.
• 26:50
  SPEAKER_01: Although we saw a much quicker reduction in the overall kind of gestalt improvement with triferritin.
• 26:57
  SPEAKER_01: In my view, looking at this data, I I really would focus more on the secondary endpoint, the PAPI score, because it does, as you mentioned, include the size of the pigmentation spots, the number and the intensity, which I think patients actually focus on much more than the overall disease severity, because if they have even one spot that's still dark, it drives them crazy.
• 27:20
  SPEAKER_01: And we see that as Durhams, we see that all the time.
• 27:23
  SPEAKER_01: And so by showing you a reduction in that, those three metrics grouped over time.
• 27:29
  SPEAKER_01: I mean, it's significant in terms of the improvement as compared to vehicle.
• 27:33
  SPEAKER_01: As early as week 20, we get statistical significance spread more at week 24.
• 27:38
  SPEAKER_01: And remember, this isn't just against a vehicle, it's against sunscreen as well.
• 27:42
  SPEAKER_01: And we know that that good use of sunscreen will reduce pigmentation.
• 27:47
  SPEAKER_01: It's always difficult, in my view, to get statistical significance against a vehicle plus a sunscreen when you're going after pigmentation.
• 27:54
  SPEAKER_01: Um, and so this is uh this is some really good data uh to show kind of what we said before, which is what we saw with the gene expression, the in vitro data is pulling through now to in vivo human data with this acne-induced pigmentation.
• 28:13
  SPEAKER_01: So, you know, this to me, Andrew, the the start plus the leap data gives me the idea that it is incumbent upon us to treat these patients throughout their entire acne journey, as we've been mentioning.
• 28:28
  SPEAKER_02: Well said, Ted.
• 28:29
  SPEAKER_02: And you know, the fact that the vehicle group plus that the vehicle group that included uh uh a moisturizer with sunscreen uh demonstrated improvement.
• 28:40
  SPEAKER_02: It almost it also supports our our treatment paradigm where we emphasize the the value of photo protection when when treating hyperpigmentation.
• 28:50
  SPEAKER_02: And uh I think it's a case of of uh selecting uh you know, in retrospect, maybe we we could have uh thought uh twice about the ODS being the primary, uh week 24 anyway, being the primary endpoint, uh as the ODS seemed to show a separation early on at week 12, uh there was significantly greater uh improvement in the overall um hyperpigmentation at week 12.
• 29:19
  SPEAKER_02: Um but uh as you said, the vehicle caught up by week 24 because of the photo protection.
• 29:25
  SPEAKER_01: Yeah, I mean it's a good point.
• 29:26
  SPEAKER_01: If it was a week, if it was a 12-week trial, we wouldn't even be talking about BAPI at all because we have such great data with the ODS.
• 29:33
  SPEAKER_01: But uh, you know, I think it's it's good, it's great data.
• 29:36
  SPEAKER_01: And with this, with the SCAR data as well.
• 29:39
  SPEAKER_01: So again, this is my kind of I'm on my soapbox here.
• 29:43
  SPEAKER_01: Uh, but I really feel like the Durham community needs to, you know, usually we say, hey, look, you've got to keep using your creams because you you're controlling the acne.
• 29:53
  SPEAKER_01: But I think it maybe it might resonate more, especially with our younger patients, to say, hey, we need to keep using the cream because all the results of the acne can be improved with this cream as well.
• 30:04
  SPEAKER_01: So we can help you with the brown spots, we can help you with the scars if you keep using the cream.
• 30:10
  SPEAKER_01: I to me, since I've had this data and I've I've changed my narrative with the patients, I feel like I've gotten better compliance through long-term use because they feel like they're still treating something versus trying to prevent something.
• 30:23
  SPEAKER_01: And I think a teenager prevention in a teenager just doesn't resonate.
• 30:27
  SPEAKER_01: Right.
• 30:28
  SPEAKER_02: And you know, honestly, um uh just as an anecdote, what I think, and I'd love to hear your your perspective as well.
• 30:36
  SPEAKER_02: I think that uh once patients are on therapy, even when they're clear or almost clear from an acne standpoint, I think the majority of my patients actually see the overall benefits to their skin uh and are motivated uh to continue using it.
• 30:56
  SPEAKER_02: They're not in a hurry to stop uh when educated about how retinoids work and the potential long-term benefits of using them.
• 31:05
  SPEAKER_02: So uh at the end of the day, they they they do see the the overall improvements in their skin beyond just the um active lesions of acne.
• 31:14
  SPEAKER_02: So they tend to be um pretty satisfied to continue long after 12 weeks or 24 weeks.
• 31:22
  SPEAKER_01: Well, I agree, and I think that's a good way to end.
• 31:24
  SPEAKER_01: So um, Dr.
• 31:26
  SPEAKER_01: Alexis, thank you so much for your time and walking us through uh the plethora of data supporting the use of triferitine for our acne patient.
• 31:33
  SPEAKER_01: Uh my name is Dr.
• 31:35
  SPEAKER_01: Ted Lane.
• 31:35
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• 31:37
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• 31:41
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• 31:45
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• 31:53
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• 32:05
  SPEAKER_01: So uh thank you for listening.
• 32:12
  SPEAKER_00: This episode of the Science of Skin podcast was sponsored by Gal Derma.