Hi, this is Pamela Jones, and thank you for the introduction on Stelfonta, and I'm gonna talk to you about Stelfonta seeing is believing. Thank you for joining us today. I have the honour of taking you from the Rainforest Discovery to the clinics and sharing you with the hard work of many field veterinarians and many researchers before that, as well as some dedicated owners and their pets.
So to Gilletigley. It is a small molecule novel diterpe ester, and basically it's a signalling molecule. So it's a little bit different than any of the anti-cancer agents you've seen in the past.
It is isolated from the seed of Fontaineia pier sperma, which is a rainforest plant, and it's unique in that it is injected intratorally, and that's much different than most of the previous anti-cancer agents that we've known in veterinary oncology. It does activate protein chinaC and I'll talk a little bit more in detail about that in a moment. But it causes direct inflammatory and oncolytic effects within the within the tumour.
And the interesting thing is you will see changes within hours and typically in most cases, the tumour is destroyed by 7 days. It was approved earlier this year by the European Medicines Agency for non-metastatic mast cell tumours. So I'm gonna talk now about probably the most important thing, and that is the mode of action.
Again, I mentioned it's a unique drug. This drug really is a paradigm shift in many ways over what we've learned in veterinary medicine and what we will learn in the future. So first of all, I look at day one and I think of mass cell tumours or any tumour for that matter.
We sometimes think it's just a cluster of bad neoplastic cancer cells. The truth is, is tumours are made up of a lot of other cells as well. You'll see stromal support cells here in, in green where they kind of look like little pseudopodia.
You also see the cancer cells there in brown, but as well, there's inflammatory cells within the tumours as well as blood vessels, and you'll notice these blood vessels are kind of tortuous and a little bit abnormal as they are in most tumours. So we inject the drug intorally and the first thing that you notice is just within hours, you notice this oncolytic and inflammatory effect. And what happens is upon injection, there's an initiation of a rapid acute inflammatory response that causes swelling and erythema within the tumour that extends out to the margins of the tumour.
This essentially isolates the tumour mass and restricts blood and oxygen supply. It also in the same process, you actually get recruitment and activation of innate immune immune cells, which is principally the neutrophils and macrophages. And so within that mass, you're getting nitrogen species, proteases and cytokines released.
Concurrently along the needle tracks where you have the highest concentration of the drug, you get actual induction of tumour cell death by oncosis. And this is actually independent of protein china, but you get organelle swelling and you actually get catastrophic cell death within those cells. So again, within that day 1 to 3 window, and again, these are all happening concurrently, you get start to get loss of that integrity of the tumour.
The vasculature becomes leaky and you get hemorrhagic necrosis. This is all due to activation of protein kinaC, specifically the beta 2 isoforms. And again, it results, results in swelling as well as leaky vasculature.
Very soon, as I mentioned, within that 3 to 7 day window, you start to get tumour necrosis and you can see from the picture on the left side of your screen that you see the tumour is starting to pull away from the healthy tissue. Somewhere by day 7, by day 14 at the latest, you will start to see that tumour slough off. You'll get full tumour destruction and what's left behind is granulation tissue in that deficit.
The really unique aspect of this drug is it not only destroys the tumour, but it stimulates wound healing. And so there's a lot of cytokine signalling going on there. You get suppression of some of the microbial activity, and you get facilitation of healing.
Specifically, this drug stimulates keratinocytes and also stimulates the fibroblast response within that wound. And then you'll see healing. And generally, again, most healing happens within the 1st 28 days.
But you'll notice also with this drug, one of the unique properties is the scar tissue isn't proliferative. It's not a prominent scar. In fact, in most cases, you end up having normal healthy tissue with very minimal scarring.
And ironically, one of the unique things too is most patients will have normal hair growth over that area. So again, just a pictorial what happens prior to treatment within hours and all the way up to day 42, is an acute localised inflammatory response, cell oncosis of the cancer cells, and finally leaky vasculature. So the European indication, as I mentioned previously, is for non-metastatic mast cell tumours and specifically mast cell tumours that are non-resectable, non-metastatic, and specifically when we talk about cutaneous or subcutaneous, it's indicated for all cutaneous mast cell tumours located anywhere on the body and subcutaneous mast cell tumours located at or distal to the elbow or the hack.
There's another caveat to this, and tumours must be less than or equal to 8 cubic centimetres in volume and accessible to intratumoral injection. We'll talk a little bit more about some of these details, but the first thing I want to talk about is this designation of non-resectable. Now, I know at the hands of some veterinary surgeons, every tumour in, in any patient is resectable or surgical or amenable to surgical incision.
However, there's a lot of factors that I think of every time I approach a patient and I have some pretty great veterinary surgeons that work with me. I myself don't, I not resecting most of these tumours. But when I think of every individual.
Patient, I think of 4 different factors, that I'd like to evaluate. One is the tumour factors, and specifically, what features of that tumour may make it more difficult to perform surgery and not only perform surgery, but obtain adequate surgical margins to where surgery is essentially a cure for that patient. Some of those tumour factors include location, distal extremities, interdigital tumours, even some on the head around the, around the face and the ears can be, not amenable to a complete surgical incision.
Size also plays a factor, of course, cause if you have a large tumour in some of those locations, even if you're the greatest of veterinary surgeons, you may end up leaving residual tumour cells behind. And finally, the couple of things that are tumour factors that we think about as well, which linked to prognosis are the grade of the tumour, either low or high grade, and as well what stages that is the patient. So does the patient have a solitary mass or does this patient have metastatic disease?
The second thing that I think about in every tumour in every patient or the patient factors. You know, certainly some patients undergo anaesthesia and they have no problems. They have, they heal well, they don't have adverse things happen after surgery such as wound dehiscent.
But then there's those patients that no matter what you do, And no matter how much care you take, they can have an adverse response to surgery or to anaesthesia, or they have higher risks due to comorbidities. And specific comorbidities that I think of are concurrent chronic diseases, or even, for instance, brachiocephalic breeds, which may be more of a risk for overall for anaesthesia. The third thing that I think of is owner factors, and we all know how pri, you know, every dog and every pet that's out there has an owner linked to it.
And, you know, owners have concerns, rightfully so. I have concerns for my own pet when I take him into to my friend, the veterinarian. But owners are concerned not only about their pet, but they're concerned about cost, and they're also concerned about what's my pet's quality of life gonna be post-surgery.
And then as well, some owners are constrained by abilities to bring their pet for surgery or recheck exams and such, so we always need to consider owner factors. And then finally, veterinary surgeon factors. Most veterinary surgeons are very talented at surgery, but I just admitted that I am not a veterinary surgeon at all.
I tend to turn to one of my, one of my cohorts and colleagues, to remove tumours for me. As well, some places may not have the facilities to perform the surgeries that we want to when they're aggressive surgeries. So one of the important factors about this drug, remember, we're going to be injecting this directly into the tumour.
So, what do we know about mass cell tumours? Well, mass cell tumours like to degranulate. In fact, any manipulation of a mass cell tumour can lead to degranulation.
I often say that if you look at it sideways in the clinic, it might swell up and bruise on you. So one of the important factors with using this drug is the concomitant medications. And I can't stress this enough because, you know, in most mast cell tumour patients, the risk of degranulation or systemic degranulation signs is probably pretty low.
But remember, we are directly irritating this tumour, so it's important that we have these concomit medications on board. And you will see they consist of prednisolone, a steroid, an H1 blocking agent, and an H2 blocking agent. H1, cymetidine, or famotidine are probably the most common that are used and H2 blocking is diphenhydramine.
And you'll see that Once we have diagnosed the mass cell tumours, 2 days prior to our intratumoral treatment, we wanna start that prednisolone. And then the other 2 medications are started concurrently on day 0, on the day of injection, and you can see they follow out for an additional 7 days. Now, the, the dose of the steroid, the prednisolone is anti-inflammatory.
You see in the beginning it's twice a day and then the last 3 days are tapered off on day 56, and 7 to only once a day. And then the drug could be discontinued thereafter. One of the other unique aspects of this tumour is the intratumoral dosing.
So first of all, we calculate the tumour volume based on what's called a modified ellipsoid measurement. And remember, you know, every time I measure a tumour, I think it's length times width times depth. And if you think about that, that really is the area of a rectangle or square.
It's not the area of a squished out, rounded off tumour or sigmoidal shape or ellipsoid shaped mass. So one of the things we do when we do a modified ellipsoid formula for tumour volume is we do length times width times depth. And then we multiply it times 1 half.
And that gives us the, the tumour volume. And then as we go on to the next step in dosing, it's 50% of that tumour volume. So we take the tumour volume and multiply it times 12, and that gives us our dose in mils.
As I mentioned previously, this drug is injected directly into the tumour. We usually try and hit a single injection point and fan that throughout the tumour mass. Pulling our needle back as we inject and injecting again into multiple areas of the tumour.
So, quick synopsis, you know, the drug is concentrated at 1 milligramme per mL. Again, our dose volume is 50% of the volume. Again, very unique because in most patients, we're either dosing on a milligramme per kilogramme basis or alternatively, we're looking at milligrammes per body surface area if we're talking about some oncology drugs.
This is specifically looking at the individual tumour volume. There is a maximum dose on the label of 4 milligrammes or 0.15 milligrammes per kilogramme, and the dose frequency is usually a single dose, but it can be repeated in 28 days if necessary.
So let's go on and talk about efficacy of a drug such as this and as well safety. Now there was a pivotal study, an efficacy and safety study done in the United States and specifically to look at FDA approval as well as EMA approval. The primary study objective was to look at the efficacy and secondary objectives were to look at safety along with tumour responses, disease-free intervals, and then looking at the overall healing at the wound site.
As another secondary objective at the tail end, we looked at owner assessment of quality of life. Because again, if you've seen the, the previous pictorials on how this drug works, it causes necrosis, it causes a wound, and we wanna know how owners are dealing with that kind of con confronting wound. The study's design is very typical of an oncology study.
It was 11 sites within the United States. It was randomised and it was investigator and owner mast. So multi-center investigator owner mast.
It was a 2 to 1 ratio with Two patients getting the treatment to every 1 dog being in the control group. And then, as in most oncology studies, dogs that are in the control group are allowed the opportunity to cross over when they're unblinded at 28 days, which is the initial checkpoint for complete response. These are pretty typical inclusion criteria for most oncology studies being age and, and life expectancy.
One of the things I wanna highlight is, first of all, it was it, the disease labels were specifically designed to the label of the drug which is cutaneous anywhere on the body and subcutaneous at or distal to the elbow and hock. The stage 1A and 3A were specifically non-metastatic tumours. And if the patient had more than 1 tumour, only one tumour was treated or injected and monitored for treatment response.
And finally, when we look at tumour size, the resist criteria of greater than 1 centimetre was to facilitate evaluation of efficacy. And an important thing I want to point out is the tumour volume was less than or equal to 10 centimetres, where if you look at the European label, it's less than or equal to 8 centimetres. So a little bit larger in this study.
And the final point here is tumour without significant ulceration, and that's important because when you're injecting a drug intratumorally, you don't want to have leakage of the drug or the product because then that could lead to reduced efficacy with less drug available for for treatment response. I won't belittle all the exclusion criteria, but very typical, the exclusion criteria are there to prevent any confusion between a drug reaction versus part of the systemic disease of a mass cell tumour. So Look at vomiting and diarrhoea and inappetence.
Those can all be part of the normal, normal disease in these patients, the naturally occurring disease of degranulation. So none of those could be included if, if the, dog had those clinical signs. And then the other ones, as far as concurrent treatments and such, again, we wanted to evaluate the efficacy of the drug directly.
And finally, the immunosuppressive doses of corticosteroids or some of the anti-atopic medications such as Apaquil or cyclosporin, we didn't, we, we excluded those specifically because we didn't know how they may or may not interfere with the local inflammatory response. Again, we didn't want to muddy the waters as far as efficacy evaluation. And finally, just some other exclusion criteria which are very typical of any clinical trial and that is basically patients that would have confounding variables or anything that would not, that would prohibit them from completing the clinical trial.
I've already mentioned the concomitant medications and these are the ones that were followed in the clinical trial. Again, an anti-inflammatory dose of steroids for 7 days, twice a day for 7 days, and then once a day for 3 days, famotidine and diphenhydramine. The tumour volume was measured with that modified ellipse, and then once we found the modified ellipsoid by that one half times length times width times depth, the patients were treated with 50% of that per tumour volume, so 50% of the volume of dose per tumour volume.
And again, I want to point out again that in this study, because it was in the United States, the label dose of maximum of 4 milligrammes was exceeded. They were allowed a maximum dose of 5 milligrammes. And finally, there is a minimum dose of 0.1 milligrammes, and that's for those very small tumours.
The reason that was followed is because if you dose much less than that, it's very hard to get this injected accurately into a tumour. Again, a single injection point and fanned throughout the mass, to disseminate the drug entirely throughout the entire mast cell tumour. So let's look at these results.
And the first thing I want to point out is the dramatic efficacy rate. So when we look at a single injection, those patients at 28 days, 75% had a complete response to this drug. And I want to point out as a medical oncologist, the first response to this I had was there's no drug on the market, there's no treatment out there besides surgical excision that has this kind of response rate.
Additionally, if we add in the patients that had a partial response, that brings our overall response rate or to 80%. And if you compare that to the untreated control, which is the lower bar, it's very dramatic, the difference in response rate. I also want to highlight here that one of the things that people will ask me is about the steroids, cause we know that mast cell tumours can respond to steroids.
And the first thing they ask me is, well, how are you measuring tumour volume? And I want to point out that the tumour volume and dose is measured on the day of injection. So that's how we measure response from day 0 is truly, truly the volume and the response day that we measure from.
They are screened 2 days prior to the injection so they can start their prednisolone and such, but they are, the volume itself is measured on day 0. Now, if we look at those patients that did not respond, were partial responders or were that, that were in that first group and we offered them to have a second injection. If we add those in, so those 18 of those 20 dogs that did not achieve a complete response, we said, all right, you've had one injection, let's add a second injection in.
We increased that response rate to 87%. So with 1 or 2 injections, the complete response is 87% at day 28. Moreover, does that response hold?
And I mentioned this was in a safety and efficacy trial, so the efficacy was measured out till day 84, which is 12 weeks. And I want to point out that of those that achieved a complete response in the first phase actually maintained. That response 96% of the time out to day 84, which was the end of the study.
I'll talk a little bit more about disease-free interval of one year in a moment, but again, holding that response was important to us. And so 96% of those patients held that response throughout the study. Oh, sorry about that.
I backed up one. So what about this wound that we create? I mean, you know, when we create a wound, this is, this is completely, again, a paradigm shift for us.
One of the first things we're taught taught in veterinary school at uni is to manage a wound, right? A wound comes into your clinic, what do you do? You need to manage it.
You need to help it heal by cleaning it, bandaging it, putting them on antibiotics, topicals, all these different things that we're. Taught to hasten wound healing. Now, remember, I told you this, this causes tumour destruction, necrosis, tumour slough, and there's a wound left behind, but it's a very healthy wound.
What I want to point out in this trial of 117 dogs, 95% of patients developed a wound at the treatment site. That's very important because one of the things, one of the number one indicators of efficacy is formation of a wound. So by day 14, 95% of patients achieved a wound.
On out of all those wounds, only 3 of those were considered more than mild to moderate. And most importantly, only 5 patients received some sort of wound management. And that's huge.
Think about it. And when I talk about wound management, I mean the use of Elizabethan collars to prevent the dog from getting at the wound. There were only 2 out of 117 patients that wore an Elizabethan collar during any time.
There was one dog that received antibiotics for an infection that was found on culture and sensitivity. Again, it was not a highly resistant strain. It was actually amenable to normal everyday antibiotics for skin wounds.
There was one dog that was bandaged and one was flushed with saline to reduce odour. So out of 117 patients, only 5 actually had management. And think about that because I think before I saw this drug, out of 117 patients, I probably would have managed 116 of them.
So the other thing I want you to look at is the left-hand side of this, and when we look at overall healing, by day 28, 56.5% of dogs had complete healing. By day 42, 76.5% had complete healing.
By day 84, which was the culmination of the study, 96.5% of dogs had complete healing. There were only 3 dogs that had not healed, and those were the three dogs with the largest wounds, but they were down to less than 3% of their original wound size by that time.
Now, as far as adverse events, I can tell you all dogs experienced an adverse event, but remember, one of the most important things about adverse events is the formation of a wound is considered an adverse event, but yet that's part of the drug's mode of action. As well as some of the other things I want to highlight here. Another important thing about adverse events is out of adverse events, 94% of them were considered grade 1 or 2, which is mild to moderate, and that means very tolerable by the patient.
There were very few that were considered grade 3 to 4, again, only 6%. And the most frequent adverse event was related to the mode of action, and that specifically is formation of wound at the site. So the most important aspect of the paradigm shift in this drug is we need to educate ourselves as to wounds and the fact that they will, will heal with mostly hand.
Of management. Again, huge paradigm shift for us to think about not managing wounds. And that means educating us as well as technicians and as well as owners because owners like to manage wounds too.
I think about how many times I've given an owner a topicals as simple as aloe vera just to, so they have something to do at home. The other thing I want to point out about these adverse events, remember, I mentioned how many were grade 1 and grade 2, but of those, if you look at these 5 things, wound formation, tumour and injection site pain, lameness in the treated limb, injection site bruising as well as regional lymph node involvement, those are all related to mode of action of the drug. So again, when I look at adverse events, I want to see those.
That's a sign that I did the right thing and that the drug is working. So finally did it last beyond 84 days, and I'm happy to report that when we look at dogs, these were, these were specifically some dogs out of Australia at 12 months, 88% of those dogs did hold that complete response that was invaluable at 28 days. So.
88% of patients at 12 months will hold that disease-free interval. Now, I want to go on to say that, that in the cohort of patients from the efficacy and pivotal study, that number was 89%. So again, we're holding that complete response.
So now what I want to delve into a little bit more is some of the things that are on the label, specifically in the summary of product characteristics. So if you take that little folded thing out of the package, you're gonna see some specific things that I want to turn your head to again because that's part of the education process of this new drug. And those major three things are degranulation, local inflammation, and wound formation.
And we've talked a lot about some of these things, but I'm gonna go into a little bit more detail once again, just so you really get the point of these things. So as far as degranulation, you know, manipulation of a massal tumour leads to degranulation. And not only are we looking at this thing crossways, not only are we measuring it, manipulating it, but we are actually injecting a drug that is gonna cause an acute local inflammatory response.
So that kind of escalates the risk of degranulation in these tumours. So we're actually inducing some inflammation locally. I cannot, cannot stress enough the importance of those concomitant medications early on, because when we talk about problems that some dogs may have, it's gonna primarily be with this degranulation event.
So, the other thing along with stressing the concomit medication importance to, to you as well as to owners is that owners need to be warned about clinical signs of degranulation. Now, we expect that local response that I've shown you pictures of, but certainly, if patients develop anorexia, diarrhoea, lethargy, even if they have vomiting or anything like that. If they have swelling that extends moderately beyond the actual tumour area, or edoema that is excessive, we need to talk to those clients about those concomit medications and make sure that they have them on board, that they haven't missed medications, that they haven't skipped them because the dog is difficult to give pills to or the dog isn't eating and can't take it in a treat.
So again, very important things about, about the concomit medications. As far as the local inflammatory action, that's, that's again, it's labelled on the summary of product, product characteristics on the SPC and again, commonly what we will see is pain on injection and lameness, very common, enlargement of the regional lymph node. These are all part of that acute inflammatory response that we expect.
It actually occurs for approximately 7 days is the average. And more importantly, that I want to stress to you is, you know, I like to anticipate that this patient is gonna have some sort of pain, and I'm going to give analgesia right up front. So I'm gonna have the owner start that immediately.
And again, as you notice from the previous photos, this really starts to work within hours before this pet has even usually left the clinic. And finally, wound formation. I can't stress this enough, as part as being on the SPC.
This is a very common aspect or adverse part of this drug, and I have to tell you, it's expected. If you have counselled your owners properly and they expect this response, then it's gonna be a lot less mitigation later. And I think of it as like when I talk to owners about radiation wounds, if I show them pictures and they know what to expect, most of the time they're OK with it.
And in fact, if I don't get that kind of response, I have owners calling me saying, are you sure you gave it enough radiation? This is the same way. If you notice when clients are educated, if they don't see a wound, they get worried that the drug is not working.
And Justine, our principal veterinarian, the first thing she would tell you is that subsequent treatments, like if a patient gets a different mast cell tumour, the owner really wants that wound to happen the second time around. Again, I can't stress enough minimal to no wound management. In most cases, you apply that covering for the 1st 24 hours as per the label.
After that 1st 24 hours, we encourage no bandaging if at all possible. And you will see rapid healing with a good cosmetic outcome. Finally, the one last thing I wanna talk about is user safety on the SPC label.
And you know, veterinarians should, you should inform your pet owner about some of the special precautions. First of all, if there's oozing, leakage, anything coming from the site, they should handle that area with gloves and clean any areas with gloves, and prevent children from being exposed to that, that oozing, fluid. .
Most of all, and, and you don't want to inject yourself, part of the protection as far as injecting, while you're injecting the drug as personal protective equipment, specifically gloves and protective eyeglasses. And most of all, adequate restraint. So, you know, the one thing that I do know about this drug and all the pre-clinical work is, you know, if you inject this drug in normal skin, you get a mild inflammatory reaction.
You do not get the necrosis and such, again, because the mode of action. Is specifically towards the abnormal blood vessels and the cells within that tumour. So again, normal tissue will have a mild reaction, but you're not gonna get the inflammatory hemorrhagic necrosis and leakageness and activation of protein china in the normal blood vessels.
So the idea though is you want the dog adequately restrained. You know, if you can if you can obtain a fine needle aspirate for diagnosis with the dog awake, you could probably, adequately restrain the dog for injection of the drug. Definitely use a lurelock syringe when you administer the product so that, that needle doesn't tend to come off of the syringe under tumour pressure, and, and finally, The biggest thing is, is, you know, again, most patients don't require anaesthesia, but you may have an unruly patient or you could have a site specifically say around the nose or something that the dog may not appreciate being injected wide awake.
But for the most part, you can inject these patients fully awake or with mild sedation. So I wanna move into real quick a a particular patient, show you kind of something besides what I showed you at the very beginning along with our cartoon pictorials of what's happening. This particular patient is an 11 year old Jack Russell terrier, with a subcutaneous mast cell tumour on the medial aspect of the elbow.
This dog has an excellent quality of life, according to the owner, has had previous mast cell tumours at different sites surgically removed. At this particular presentation for the clinic. Study actually has another mass cell tumour on the left carpus and actually had a possible one that hadn't been diagnosed yet on the right lateral leg.
Again, as part of the protocol for the study, this patient could only get one of them injected, so they chose the largest one. This dog also has, tracheal collapse. And so, the owner kind of wants to avoid anaesthesia cause the last time you had anaesthesia, the dog coughed for a good week or two afterwards, due to tracheal irritation.
So the body weight you can see is 6.6 kilogrammes and we started prednisolone, on, on the, the diagnosis day, two days prior to your injection, and we got doses for the diphenhydramine and famotidine. So let's move through this.
This is day 0. We've diagnosed it. You can see it's really hard to get a good photo of this one because it's one of those indistinct ones that you kind of really can't palpate the edges.
I will also note here that on the very bottom of your screen, part of control group received to get a treatment on day 30. This dog was in the original phase stratified to the control group and in day 28, obviously we could still see a tumour there. We measured it.
We said, hey, guess what, we've unblinded you, you're in the control group. Would you like to receive the drug? And this drug crossed over.
The tumour on day zero measured 1.6 by 1.6 by 0.4, so one of those flat indistinct tumours, and the tumour volume was calculated at half a centimetre cubed.
The dog received 0.3 mils rounded up to the nearest 0.1 mL, so 0.25 is the dose, and it was rounded to 0.3 mils.
And the total dog dose Migs per kg, remember we have maximum doses we can give, was 0.05, so it was actually very well within the range of injection for this dog. Now, here, this is literally within hours we start to see this kind of bruising and swelling and you can even see at the, at the proximal aspect at the top of your screen, you can see the redness where it almost appears like it's starting to, the area is starting to slough away from normal skin.
Definitely within 2 hours, there was bruising, swelling, pain, and heat. This dog by preference of the veterinarian was started on tramadol. I will tell you in the study, there was tramadol, gabapentin, buprenorphine, and several others.
Those were the three common ones that were used for pain. And again, we do recommend avoiding non-steroidals as these patients are on anti-inflammatory steroids at the time and we don't want overlap of those two. Pain in this patient was not rated as an adverse event again, because this patient had adequate pain control and the owners felt the quality of life was still excellent.
So here we are at day 7, and, and we've obviously got a necrotic SR in the central aspect of that that has not sloughed off. I wanna highlight that look at how distinct and nice those edges of that wound are. You know, this is one of those wounds that I would, if it came into me, I'd be like, wow, well, we need to get rid of the necrotic tissue, but The wound edges look healthy and I don't need to do anything surgically.
Specifically in this treatment, and I, and when I say that, I mean a wound that just comes to me from an injury. This wound, we know it is induced by tilinol tibulate, elfonta. And so, we already know that we're seeing granulation tissue and such.
So this wound doesn't need any further management. In fact, the dog had access to it if they wanted to look at it. Noe collar or anything like that, and there's some healthy serious discharge only from the wound.
This maximum wound was size was formed at day seven and was 3.2 by 2.1 centimetres across.
So here we are at day 14, and again, you can see very nice healthy granulation tissue. The wound is starting to contract and the wound is actually reduced. Now it's down to 2.6 by 1.5 centimetres.
So it's already starting. This dog actually was started on some gabapentin, not for the forelimb, but the dog also had some rear limb, lameness and possible osteoarthritis in again in the rear limb and was started on gabapentin at day 18 for one week. But again, unrelated to the treatment site.
So again, here we are at day 28. There's a small scab at the, at the treatment site. This was deemed as a complete response and the quality of life was rated as 99 out of 100 by the owners.
And here we are at day 42 and I can't emphasise enough that the scar tissue that's present is usually very minimal. And so, so you usually have an excellent cosmetic outcome. I'm happy to report that this dog, actually was, tumour site-free at 12 months, so the treated site held that disease-free interval until 12 months and is doing very well.
So one final thing that I want to end with is, is kind of some highlights of some final tips for success. One, I can't stress enough the importance of the concomit medications. And again, because we're, you know, deep granulation of mast cell tumours may not be that common in our usual patients, but we are specifically injecting a drug where we expect an acute inflammatory response.
Finally, you know, educate owners. You know, not only is, is our goal between Verva and cubiotics is to educate you as to what Steelonta does, how it works because it's such a paradigm shift. We want the owners to know what to expect, get them engaged in the whole process, and you're less likely to get phone calls and have problems later.
And I think what I've seen already in, in the, veterinarians. Throughout Europe that have had the drug for a couple of months is that they feel initially they're kind of worried about the wounds and then as they get more and more comfortable with the drug, they're more and more comfortable with what clients know and how they educate clients. And I will tell you, Vervac is excellent.
They're providing you with tonnes of educational tools and pictures and cases to where you can share those with your clients as well because a picture is worth 1000 words. Again, if you can perform a fine needle aspir conscious, you more than likely will be able to do stuff onta consciously. One of the tips from Justine, who is our principal veterinarian, she's treated well over 500 dogs in the, in the past few years.
And she says, you know, if you pull up that dose of selfonta and just let it reach room temperature on the counter for a few minutes just prior to treatment, it may have less of an irritant effect on that injection. That's just kind of her observation. So another little tip from her.
Fanning is very important. You really want to ensure maximum exposure of the tumour throughout the the drug throughout the tumour, and you wanna try and stick to one injection point. We know that these tumours can ooze and bleed when we injection inject them due to the heparin and such throughout them.
As well, we don't want drug leakage by multiple tumour injection points. Recommend wait 28 days before the next treatment, even if you think the drug has not worked and you're seeing like a nodule there at 14 days, I encourage you to try to wait if at all possible till 28 days because some of these will dramatically change between day 14 and 28, and that scar, that, that presumed recurrence is actually scar tissue and inflammatory tissue that's shrinking down still. We talked about the hands-off healing.
Certainly, the, it is, it is labelled to protect the site with a a light covering for the first day, following injection to collect some of, if there's any potential drug leakage thereafter, hands-off healing and leave off bandages where it all possible. One thing I didn't cover earlier that I wanna highlight very quickly with regard to the label, one of the things that's unique is, is the subcutaneous mast cell tumours treated distal to the elbow or the hock. Part of that is because a subcutaneous mast cell tumour that occurs on the trunk is beneath, Trunkal muscles, it's deep within the subcutaneous tissue and there's two caveats to injecting that tumour.
First of all, before I talk about the caveats, I'm gonna tell you that the drug is still efficacious at at that location. The problem is injecting that location, you have a high probability that you could that you could miss a small mass cell tumour and just inject the surrounding fat tissue in which your efficacy would be very low. The second thing is when you inject a tumour in that subcutaneous tissue and you have that inflammatory process that happens, What happens is that, that sterile necrotic area is actually trapped underneath there and it looks for a way to drain, much like an abscess would.
Again, it's a sterile necrotic area and you could have to, you may develop some drain. Tracks or you may have to enable that wound to drain. So when these tumours, when the subcutaneous tumours are located distal to the at or distal to the elbow or hock, they develop their own draining tract because they're very near the surface of the skin.
I hope that has helped you guys learn a little bit more about Stelfonta. I wanna thank you for your time and, finally, the last thing I wanna say is, is, you know, for more information about Stelfonta, please contact your local Vervak territory manager. If you have any information regarding these slides, please don't hesitate to contact me.
I've put my contact information. There both my email as well as my cellular phone. Again, please don't hesitate to contact me or your er back territory manager.
And finally, if you, I have references at the end in the slide deck if you're interested in any of the topics I discussed, and I'll be happy to answer any questions during the Q&A session. So again, thank you for your attention today. Pamela, that was absolutely fascinating.
And I'm sure I'm not the only one that says that you have rearranged my mental furniture substantially tonight with this drug. It has been very, very interesting. So, thank you, Pamela, for your time.
And once again, a huge big thank you to Ver back for their sponsorship this evening. Pamela, we have, as I said, rearranged some mental furniture and, we have lots and lots of questions coming through. There are a lot of themes that are running through the questions, so I am going to be paraphrasing quite a few questions.
One of the first questions or, or themes that are coming through, Pamela, is the story of different sites of tumours, like on your Jack Russell that you had there, you mentioned that the dog has got different tumours, at different sites. Would you divide the dose that you've calculated across multiple tumours up to your maximum I'm talking about. So you, you dose each tumour to their size to the maximum dose, or how long would you wait before you repeated the treatment on multiple tumours?
That's a great question. And actually, that's one of the things that I like about this drug, and it's a great indication for the drug actually is those, those patients where you have 245 tumours or you've taken many off previously and you're just tired of doing surgery or the owner's tired of you doing surgery. And what you need to do is calculate the total volume for each tumour.
Calculate the doses, the total dose for all those added up, and then you, the only thing you don't wanna do is you don't wanna exceed the maximum dose for the patient. And the maximum dose for the patient is 0.5 milligrammes per And the total maximum dose can't exceed 5 grammes.
So if you have a very long and it calculate out to 5 milligrammes, the highest you can calculate, the highest you can give is 4 milligrammes. Now, the, the probable conundrum that you may have there in some patients is you have, you know, 4 or 5 tumours and the maximum dose is would be exceeded. So then what I would encourage you to do is pick the top 3 tumours, treat those tumours, and then 28 days later, come back and treat the remaining tumours.
So you don't exceed that maximum dose at any one treatment cycle. So obviously your maximum dose then is per 28 days. And how, how many times can you repeat?
I mean, if you've got a dog that's, that requires 45 or 6 different tumours injected, could you do that every 28 days? Very good question. And yes, you can.
There is no maximum amounts you can treat. And the reason is, is the drug is held pretty tightly to that intra-tumoral location and, and doesn't enter systemic circulation except for tiny nanograms. So it's very safe to inject multiple times and if you talk to Justine, there's some dogs in Australia that she's managed for up to 5 years with these tumours that just pop up everywhere.
OK, excellent. Another couple of, of, or trend of questions that are coming through is, on the use of, of different drugs and concomitant treatment. Now, obviously, you've gone through your H1, your H2, and your prednisolone as being almost mandatory treatments when you're using this drug.
But are there any drugs that should be avoided? In other words, if the animal is on drug X, then we should not be using, the steella Fonte. Yeah, that's an excellent question too, and, you know, in the efficacy and safety studies and, and the one that was published, there were no restrictions on other medications, even over the counter supplements and such, unless it was thought to interfere with the immune system or the immune response.
So, certain drugs were excluded for that reason. However, No other medications were excluded. So, I think of if you have a patient that's on medications, the first thing to think of is, does it affect the immune system or the, or a potential immune response?
And if so, then you might want to try to wean them off of those medications for the temporary being of the treatment. Now, with that said, you know, the, the other thing is when we look at pharmacokinetic studies, it's only nanograms of the drug that is, is, detected in the peripheral blood, urine, and faeces. So nanograms, you're talking 100,000 fold less than the milligrammes that you're injecting locally.
So when you look at that minute amount, the chance for interference or interactions themselves between drugs is probably negligible, if at all present, and the time for the, that, that drug is detected in circulation is literally within the hour, it's excreted and gone. OK. Another theme we've got coming through from Koshima and quite a few others, is about, working out the volume of the tumour, and sometimes tumours are quite hard to measure the depth of them.
Would you overestimate or underestimate, and is there any risk of locally overdosing, we're not talking about the maximum dose per dog, but we're talking about per tumour. If you were worked out that, the tumour needed 0.3 millilitres and you gave it 0.4, would that be detrimental?
Yeah, actually, you know, that measuring tumours, despite I've done it for 20 years, I agree. Measuring depth of most tumours and lymph nodes and such is probably the most difficult thing to do. And, you know, I would recommend overestimating rather than underestimating.
In fact, if you look at the study and you look at some of the patients that I can highlight clinically, If it's calculated the dose to be 0.25, we actually recommend rounding up to the next 0.1 mL.
So a 0.25 would get 0.3.
And, and again, overdosing should not lend itself to any problems when you're talking about tumour volume. And underdosing actually, the problem is you could you could result in a loss of efficacy. I think I saw in that same kind of general feed category and thought process is, what if you miss a tumour and that's those subcutaneous ones where you get part of the dose in the tumour and then you get part of it just in the surrounding fat.
There is a lot, there could be a potential loss of efficacy. And, you know, all of the study, veterinarians that I talked to, and even talking to Justine and Graham and some of the veterinarians in Australia, they say, oh yeah, the first couple times I wasn't as confident, but as I got better and better at the procedure, I feel like I got better and better in efficacy. OK.
That's, that's really interesting. And another theme that's coming through is this, decision on which tumours to inject and which one's not. And, and, you know, how do you distinguish between cutaneous and subcutaneous?
How do you know, you know, what grade they are and whether they're metastatic and, you know, should you stage them before you use the drug, all those things? Yeah, those are all really good questions and, and, you know, a lot of that just speaks to appropriateness of case selection. You know, I, I always say, I, I think if you, if you were to call me as a veterinarian and say I got this biopsy from a mass cell tumour and the first thing I'm gonna ask you is what grade was it and was it marginally resected or was it completely resected?
And those are very important things. And now I'm talking about a tumour that we inject intratorally. So how do we get that information?
So first of all, grading cytologically is coming more into acceptance. Now, much like it took 10 years for us to go from 3 grades of histologic grading to get more accepting of a 2 histologic grade, a two-tier system. Cytological grading is gonna take a good 10 years to really fall into high favour, in, in my opinion.
I think a lot of oncologists don't reject it, but it's one of those what's the gold standard. The other thing about gold standard and, and grading and histopathology is we always call histopathology as gold standard, but the truth is, I use more than just a histologic grade to determine what's best for my patients, and that includes physical exam. It Its history.
If a, if a patient comes in with a mast cell tumour and they say, oh, that thing's been there 2 years, I know that 99 times out of 100, it's gonna be low grade. If they come in and say, it showed up last week, it's growing really fast, bruised and, and swollen off and on, then I know it's behaving more like a high grade tumour. And also with histopaths, sometimes we use the advantage of doing some of the immuno histochemical stains and, and looking at things like some of the, molecular factors and, and factors of division that we look at like mitotic index and such.
Some of those can be looked at on cytlogic grading, but others can't. Now that kind of goes into grade and stage. Staging is really important in mast cell tumour patients when they're a higher grade.
So what I say is look at all those parameters that I mentioned just mentioned some of them, look at the patient entirely, as well as the tumour characteristics and say, OK, is cytologic grade gonna give me the information I want. If it's not, and we're still worried that we need to do an, an incisional biopsy to get a grade, it's reasonable to do an incisional biopsy, but you probably want to wait a good 14 days to let that site heal. So you don't have leakage of the drug when you inject it because leakage of the drug would be underdosing and you could lose efficacy.
I am the first one to say that when I do, when I first started seeing patients as an oncologist, I staged just about everything to the complete max. And then I realised, wait a minute, is that reasonable? I'm not saying it's not wrong.
What I'm saying is I developed a more reasonable method of staging. First of all, mass cell tumours, I think every single one should be diagnosed in every, at least cytologically, and I think every single One should be graded cytologically, if at all possible. I think also that regional lymph nodes, you need to take a step beyond just palpation because I've palpated hundreds of thousands of lymph nodes, and I can still tell you that I need to do a fine needle aspirin or a biopsy to tell if a lymph node is positive or not.
Palpation alone. And there's been studies that have shown that that normal palpating lymph nodes does not mean they're not metastatic. And same goes for when we get those high grade ones, you know, I definitely recommend staging.
If you have a high grade tumour or one that is potentially high grade by clinical factors like I mentioned, it's having degranulation events and such. I, I think you should take the step and go further and definitely stage all those masses. I hope that answered, that was a really long explanation.
I, that, that, you know, that I saw a lot of those in the Q&A section being typed out and it's a really great discussion to have. It's, there's no for any one patient, and I just have to say, you know, in my opinion, it's not absolute for mast cell tumours by any means. It's, it's each individual patient you have to assess separately.
I, I think that was an absolutely fantastic answer, Pamela, because you've just covered a half a dozen other, other questions as well. Catherine's furniture has obviously been shifted like my mental furniture has. And she's asked, why is it recommended to leave the wound uncovered?
Would wound, moist wound management still not speed up healing? See, we're, we are, it is ingrained in us to manage those wounds, and I think it's a great answer. And so the reason it's recommended not to cover is because there's also clinical data to show that wounds left to have oxygen actually can heal faster.
And it's interesting when you start seeing these wounds, you know, they do remain moist. They don't dry out and desiccate. And, and I'm saying that, and, and I've see these environments where it's hot, it's not humid.
It's dry arid conditions, and you would think that you would end up with an unhealthy wound if it's not covered and you don't. I mean, that, that's, that's part of the really remarkable things about this drug, and, and I will tell you as an oncologist. I said, wow, that's really great efficacy, and that's kind of a cool product, but this wound healing is amazing.
I mean, I just jumped to that because I've never seen wound healing like this, nor have a couple of my surgical colleagues when I show them and talk to them about it, they just can't believe that this wound, that the wound healing is so, so fast and so healthy without intervention. But you said that that was stimulated by the drug. Absolutely, you know, cause I've had other people say, well, what if we went to like wet to dry bandages and such, and, you know, when you start doing that wound management, you're probably interfering more with the drug's effects than you are helping the wound close.
Excellent. Yeah. Really interesting question here and one that I never even gave a second thought to, but well done, Peter.
What size needle should we be using? It's a great it's a great question. You know, most often a 23 gauge needle, and length is all up to how long the tumour, how big the tumour is, you know, can you adequately, your whole goal is to inject through one point and Fan it throughout the tumour.
So if you have a tumour that is, say, 2 or 3 centimetres long, you wanna have a needle that's gonna cover that. So you definitely wanna go to, you know, your 1 inch and a half needle type thing to cover that 3 centimetres. Yeah, yeah.
And the one, the one site, but the, the fanning and the, the sort of spreading the, spreading the love, as it were of the drug through the tumour is important. Yeah, and you know, it's, it's the way I describe it, we do have videos that Verbe can show you as well, your representative can show you, but the way I describe it is when I aspirate a tumour and I'm doing a true aspiration where I have the needle on the syringe and I'm suctioning back. It's almost like I'm doing the opposite when I'm injecting this.
And think of like when you infiltrate lidocaine, you know, you inject, you draw back to make sure you're not in a vessel and then you inject slowly as you withdraw the needle. That's the same process you're doing to distribute the drug. Redirect, inject slowly as you withdraw, redirect.
Yeah, yeah. Pamela, a lot of, a lot of, people are asking, about reshowing slides and everything else. So, just to, to, to put you on hold for a second there.
Folks, we can't go back and show you slides. This was a recording, but what I can stress once again is, we are recording this presentation and all these questions as we did with Owen's fantastic presentation last night, and they will be up on the webinar. Vet's website within a day or two.
They, the technical guys are absolutely fantastic. So just go to the webinar vet website and you will be able to find these recordings there. The recordings can be paused and rewound and shown again.
And so any slides you want to see, you can actually pause it and take down the information or watch it over and over again. It really is very, very, very helpful. Pamela, there are loads and loads of accolades coming through, and I see that one of my classmates, Marie Potgeter from South Africa, has also said, thank you, Pamela.
Thank you, Verbek. We, will we get this drug in South Africa? Marie, the answer to that is you contact your Verbek, representative.
Each country will have its own, regulations for distribution and everything else, so we can't give you answers now of specific, countries, but, certainly talk to your local VA representative and they will be able to help you with, distribution in and around your practises. Pamela, there's another question here. If there's no systemic uptake, why are we worried about maximum doses?
That's a very good question. And, and it's, honestly, a lot of it is regulatory. When we look at, when you look at getting a drug and testing safety and efficacy, you set parameters that you know are gonna be efficacious as well as safe for patients.
If you look at, for instance, what I will tell you. In the United, if you look at the size of tumours overall, in the United States study, there were 3 tumours out of that 117 that were treated that were actually 123. But there were 3 tumours that were above 8 centimetres cubed, but yet they were below 10 centimetres cubed.
So a very low numbers of those tumours. And if you look at those patients with larger tumours, they have a higher risk for degranulation events and a higher risk for adverse events. So that's why the parameter is set at that.
So again, you know, even though the drug may not go systemically, if you have a degranulation reaction, it can, you know, obviously the histamine and such can travel systemically and cause a patient to be very ill. And so that's the main reason. Right.
And I get that ties in with one of the other questions that Peter has asked about using other drugs after these injections if there has been spread to the regional lymph nodes and follow-up treatments with chemotherapy and those kinds of things. Yeah, so the indication for the drug is non-medicine. However, I often get the question, well, what if I use it for local tumour control?
Again, indication is non-metastatic, so that would kind of be off-label. But I will tell you that there's been no widespread studies or in-depth studies looking at large groups of patients with concurrent medication like chemotherapy and such. Those studies would just be too cumbersome.
I, I think I will say stay tuned because we're looking at further studies, what we call phase 4 studies after approval. And one of the big things that, that oncologists have brought up to me is what if I use it and then down the road, I need to use chemotherapy concurrently because we have something more aggressive or for instance, a non-metastatic high grade tumour that I want to preemptively use chemotherapy. I would say if you have to use chemotherapy, definitely let them get past that healing phase, you know, to where you don't have open wounds or delayed wound healing.
OK, fantastic. Lots of mental furniture being shifted around tonight, Pamela. You've really rearranged the furniture.
Martine wants to know, is there a disadvantage of using bandages because she's not convinced that, clients wouldn't prefer that open wound to be closed with a bandage. Yeah, so what, again, the hardest thing is, is doing head to head studies saying, you know, we did 20 patients that had bandages and 20 patients that didn't have bandages, right? That's a very hard study to do because you have different locations, you have different activity levels of patients, you have different size wounds, so it's a very hard study to do.
I will tell you of the researchers that have been looking at this drug since 2012, their inclination is in most instances when they see edoema delay wound healing and such is when two things are done, when the wound is bandaged or covered. Consistently. And when the patient, believe it or not, and this, this is again, completely a paradigm shift from what I've been taught, when the dog has a knee collar on and doesn't have access to the wound, you want them to actually groom and encourage that tumour slough.
Clients don't always like to hear that. They don't want to see an unsightly wound sometimes, and sometimes they don't wanna know that their dog is actually licking at a sight. But it's interesting that when you look at the 500, 600 patients or more that have been treated in Australia, that is what all of the veterinarians say is every time we interfere with wound because it's big and ugly and, and whatever, if we bandage it, we end up having more problems than we feel we help it.
That's gonna be an experience thing, and I didn't catch the name of who asked that. But you're exactly right. I have started, you know, I look at a lot of cases where that'll just send me a photo and say, does this look OK?
I want to put a bandage on it. And some of them, I have to tell myself, no, you don't want to bandage that. I have to reiterate it, despite all the ACs and the, the, education I've had and how many I've followed up on, it's still hard for me to say that.
It's still hard for me to say no e-collar. So, that's my biggest thing is, gosh, you know, try your hardest not to bandage, if at all possible, but I understand the inclination. And you'll learn with experience.
Not only have you rearranged all the furniture, you've now gone and broken it as well. I, I think I know the answer that you're going to give, but there's a lot of questions coming through about, antibiotics, and, and I'm hoping you're going to say no, you don't need because the granulation bed, but if you want to pick that one up. It is there, I'm sorry, I didn't catch how that was phrased.
There, there's a lot of people asking questions about, using prevent antibiotics as a precaution or just in case. . Yeah, yeah.
So in, in the studies, the efficacy and safety study, you know, we allowed antibiotics if you would like to, and you'll notice that if you read through that study, quite a few patients had antibiotics. Some were just prophylactic antibiotics. Some were on antibiotics for other skin things, or other indications, and again, we weren't gonna exclude those patients because of that.
You know, it's amazing, you know, the, the guidance that I've learned is really in the vast majority of cases, you do not need antibiotics. They wouldn't be indicated. Now, when I say antibiotics, I would jump on them.
So you're gonna have with a necrotic tissue there while it's there and that's say 3 to 7 day, 14-day window. Necrotic tissue has an odour. I mean, we have to recognise that.
And so that's when I would expect to have some amount of odour, but once that tissue has sloughed, that odour and any discoloured discharge should disappear. If that wound looks like it's healing remarkably and there's no discharge, and then suddenly I start getting discharged, that's where I'm gonna say, you know what, I need to step in because I think I could have some opportunistic bacteria in there. Yeah, absolutely.
And, and I mean, we know that granulation tissue is stimulated by this drug, and granulation tissue is one of the best natural antimicrobials around. Yes, yeah, and, you know, it's amazing because even some of the early studies and so if you look at some of the studies that are done looking at in vitro work, there is some, there's evidence that this disrupts that biofilm that forms and protects bacteria, which that is just some phenomenal work. I could not believe that when I was reading through some of that.
As well, it has a stimulation to keratinocytes, some of the simple tests you can do to look at keratinocyte function. It stimulates those. And the way I say it about fibroblasts, why you get very minimal scarring is, it's almost like it stimulates the yin yin and yang of, you know, of, of fibroblast production just enough but not too much.
Cause again, scarring is an, is an overresponsive, of, fibroblasts, where this ends up with a nice soft wound. There were some patients that I followed up when I was in Australia. On my last visit that I was like, OK, you want me to find where the mast cell tumour was, and they showed me the picture of the mast cell tumour and the scar and the healing and how big it was, and then I could barely feel a scar anywhere on the patients sometimes.
Fantastic. And hair regrowth too, that was the amazing thing. Yeah, yeah.
Well, your pictures showed that there was good regrowth there. Question coming through. The, the sort of drastic effect of the necrosis and that if used perianal and perennially.
Yeah, good question. So the two questions I often get is, one, what if you put it into normal healthy tissue, and again, you get a mild inflammatory response. The second one I get is, what about these tumours that are near the eye or near the perianal region and, and that needs to be done with caution.
The number one thing that I think of as an oncologist when I do radiation even is If the tumour has destroyed something, whether it be the skin or the tumour has destroyed a muscle or the tumour has infiltrated a bone, not like mast cell tumours, but if it's done that and destroyed that, if I destroy the tumour, what kind of hole am I gonna be left with? And that's a very blunt way to say it's not going, if it gets rid of the tumour, you're gonna be left with what's healthy there, not left over stuff that's already been destroyed. So I use it with caution in those areas.
So if I have a perianal tumour, I'm gonna say, OK, it's gonna heal on its own. I'm gonna tell the owner maybe we should do some, if it's like below this or something and it's gonna have for faecal contamination. I may say, let's do some water lavage after the patient defecates or a couple times a day to keep the surface, you know, free of, of collecting debris.
But I'm also gonna realise that if it is actually infiltrating right into the area, the anal tissue or something, that I may have to intervene at some point. You could have over scarring because of the sphincter muscle. So it's gonna be a case by case basis as to, you know, what kind of cautions we have to take.
And it's the same with eyelids. You know, eyelids are always, is, if it's involving the eyelid, how much of the eyelid may be destroyed by the tumour and what are we gonna have to rely on for normal function and healing. And sometimes those are cases where we either opt for surgical incision, we opt for the drug knowing that we may have to go in and do some sort of correction, later, but not always.
You know, I'm amazed at how these heal. Excellent. Really interesting question, from Caroline.
Are these vials single use or they're multiple doses in a bottle? Yeah, they're single So they come in in the single-use vial with 2 milligrammes. 2 milligrammes per bottle.
OK. The, other, trend of questions that we've had a lot of, Pamela, is about the analgesia, for how long and what would be your drug of choice? Yeah, good question.
So in the study, we allowed analgesics to be at the discretion of the attending veterinarian, and if you talk to Justine, she said, you know, in the majority of cases, she uses or she at least sends home some form of analgesia for the owners to use if necessary. Remember, the steroid is on anti-inflammatory, but it's a very short period after that you've already weaned him off the steroid for anti-inflammatory. In that trial, the choices most common were tramadol, gabapentin, and buprenorphine.
I am a huge gabapentin fan. I, I've just, you know, I will tell you 15 years ago, I used Tramadol. Now, I rarely use tramadol and I more commonly use gabapentin based on, my own personal experience, but based on some of the studies that are out there on the pharmacokinetics of the drugs.
And so it's gonna be really dependent on what you feel is the best for any given patients. If you Look at that study, I think it was just 60%, like 63% received annual. The, or the mean days was days and the average was 9 days.
And you can imagine when that inflammatory process is happening within that 1st 1 to 3 days, that's probably the most discomfort you're gonna see. Most of the, most of the veterinarians that have already dealt with the drug, including, Justine and several of the investigators say that, oh yeah, by the time that tumour sloughs, most patients aren't bothering the site. They don't seem painful.
They're usually not licking at the site. They tend to just leave it alone once the tumour sloughs. OK, fantastic.
So again, as you say, it it's, it's a case by case basis. Yes, yeah, definitely. We've had quite a few questions coming through related to side effects specifically of the steroids.
Do you find this is a problem when they're on H1 and H2 blockers as well as steroids? Yeah, if you, if you look at the adverse events in that, in that pivotal study, you know, one of the things that, that was in there was, polyuria, polydipsia, and, you know, more than likely, cause that was also in the control group. And in, in that study, the control group got the concomit medications as well.
So it was Very well done in that manner. And there was polyuria, polydipsia in both groups. And fortunately, that time period being anti-inflammatory and being a very short time frame when they're on the steroids, you know, it's very short term, not long lasting at all.
And if, if you felt the side effects were, were quite severe, would you, would you risk stopping the steroids? Yeah, I, I would recommend if at all possible, not. That would be like a last resort to stop.
Those concomit medications are very important. Not only that, that the, you know, the biggest thing that we recommend is follow up with the owners, have your technicians follow up and check on the patients and say, after one day, have them call them and say, OK, are they getting all their Medic medications. Because again, in most instances where we find they are not eating as well or they're a little off or they maybe have vomiting, it's because the owners couldn't get the medications in them.
It's that kind of thing where they're like, I just can't give them the medications or they forgot. Invariably, it's one of those where the owners forgot to give the medications. Fantastic.
Pamela, I think we have covered most of the questions. I have just posted the website, in the chat box for those that are asking for reruns and re-explains and recaps and everything else. These are recorded last night's presentation from Owen, Pamela's presentation tonight.
They will be on the website of the webinar vet. Go and have a look. You can rewind, you can stop, you can watch over and over.
But unfortunately, tonight is not possible for us to go back and watch all of those. So, Pamela, it is with great thanks and shifted mental furniture that I thank you for your time tonight. Oh, thank you and thank you to everybody for your attention.
If we didn't get to any questions, I'll be happy to type out some answers for webinar vet or for your Verba representative. I'm always available to answer questions. Thank you very much, and I think you'll find if you look through the questions, there are huge accolades of brilliant presentations.
Wonderful. Thank you for all the amazing knowledge you've shared and it just goes on and on and on. So it's not only me, it's a general feeling that it's been fantastic, Pamela.
Thank you so much. And to Vur back as well, thank you so much for your generous sponsorship of last night and tonight. It really has been an absolute pleasure to be able to host these, presentations, and thank you to Verbe for that sponsorship.
To my controllers in the background, Jamie and Kyle, for all their help in making it work smoothly. Thank you very much. And lastly, to all of you that have attended, I hope you've had as much joy out of this as I have, and I look forward to seeing you on another webinar.
Good night.
