William Huang: Thanks, Sam. Thanks for the invitation, and thanks for giving me an opportunity to talk about the poster that we presented at this year's GU ASCO. So, we presented some ad hoc analysis from the ENVISION study. And those of you who may not be familiar with the ENVISION study, this is a phase three single-arm trial using UGN-102 for the treatment of intermediate-risk low-grade non-muscle-invasive bladder cancer. Now, this particular trial is the one that did allow for a pathway for FDA approval for UGN-102 for intermediate-risk low-grade non-muscle-invasive bladder cancer. So in this study, patients received six weekly instillations of UGN-102, which is a reverse thermal gel that's bound to mitomycin. And the primary endpoint of this study was to look for a complete response at three months of primary chemo ablation of these low-grade tumors. Some of the secondary endpoints included the duration of response at 12 months and 24 months as well. Now, this particular data that we presented on this poster was a post-hoc analysis, looking at the outcomes of patients based on their EORTC score subgroups. You can see here that they were broken down into three subgroups, a low score, one to four, intermediate score five to nine, and then 10 to 17.
Most of the patients received all six instillations, and you can see that most of the patients had multiple bladder tumors at the time of treatment, and most of the bladder tumors were small and multifocal. And you can see the breakdown here. 31 patients in the cohort were in the low group, 191 in the intermediate group, and then 15 in the high-risk group. So here you can just see the Kaplan-Meier plot in terms of the duration of response of complete responders based on their group score, low risk, intermediate risk, and high risk. And you can see that there is some differences in their Kaplan-Meier plots, but overall it was generally quite similar regardless of the risk group. So we can go over the details of the results in a little bit more detail on the next slide. Across the board, essentially 83% of patients, or 82% of patients, ultimately had a complete response, but you can see that the complete response rate at three months was lowest in the high-risk group. Nonetheless, this is a group of patients who've had recurrent disease, all low grade, and had treatment of their bladder tumor with primary chemoablation. Then, when you look at the duration of response and the likelihood of being event-free at two years, you can see that it was quite high, ranging anywhere from 60 to 67%, 66%, up to 73% at two years. So, this demonstrates that not only is use of this in this population effective in terms of chemoablation, but it also provides a very high duration of response up to two years, irrespective of the risk group score.
So in conclusion, you can see that UGN-102 does have a high complete response rate across all the groups, and the majority of patients did remain recurrence-free at two years, which is pretty remarkable considering that these are all recurrent patients, and some with recurrence scores as high as 10 to 17. Interpretation of this, however, may be limited by the small sample size. Nonetheless, in this post-hoc analysis, we believe that we did demonstrate that UGN-102 provides a durable and a clinically meaningful response, in terms of disease control for this patient population.
Sam Chang: Bill, that was a great overview. To remind everyone, this product is the product that is the reverse thermohydrogel that stays in the bladder that comes to you where you need to keep cold.
William Huang: Correct.
Sam Chang: And then basically once placed in the bladder as the temperature rises, this actually goes from an aqueous solution to something that's more of a semi-solid. So I think an important thing to emphasize probably is the fact that this is a different treatment algorithm, in terms of the fact that just as you emphasize, these are tumors that were still in place. This is chemoablation. This is not post actually resection. So a couple of things to ask about. Clearly, you saw small numbers in the outline groups, the lower recurrence and the higher. But I think what I was struck with was, okay, you definitely have these patients that tend to recur quite a bit. That was the group in the higher, greater than, I guess EORTC risk score greater than nine, that higher group, a few that did have evidence of disease at three months. So still though, six out of the nine CRs, correct at three months. Is that right?
William Huang: Correct.
Sam Chang: And I think then to me, the most impressive is what you then pointed out was the duration of response afterwards. And that's, remind me, that's without maintenance, correct? That's just with the six instillations?
William Huang: Correct.
Sam Chang: Okay.
William Huang: Correct. So as you mentioned, this is a reverse thermal gel, which is aqueous when it's cold and becomes solid, semi-solid gel-like, when it raises to body temperature. And this doesn't allow for then a dwell time of up to six hours of exposure to this mitomycin-bound reverse thermal gel. There is no maintenance doses, and this was an induction of six doses. But as you pointed out, this was the primary treatment for these tumors. This was not an adjuvant treatment. This was not a post-TUR, a complete TUR followed by administration of this. So this was a treatment by which this reverse thermal gel was actually used to primarily chemoblate the bladder tumors. And as you also mentioned, it's highly remarkable, because not only did it provide a complete response in the majority of patients, but the duration of response up to two years was pretty profound.
Sam Chang: Yeah, I think that's what strikes me as much as anything is that, with this treatment, clearly you have this field effect within the bladder. These are the patients with these multiple tumors, and that we're probably much more successful with this kind of strategy as opposed to repeated TURs and fulgurations and that type of thing.
William Huang: Correct.
Sam Chang: Tell me how this has become FDA approved. Tell me how you use this now in your day-to-day practice. What types of patients, what types of clinical situations and scenarios? Because clearly it's not for everyone, clearly focused on the FDA-approved indication of low grade and recurrent intermediate risk. But tell me how you've adopted it in your practice.
William Huang: So, I think for a lot of us, we recognize, during the duration of the patient's treatment course, that you will have a number of patients who are frequent recurs. So you scope them, you start off by doing a complete TURBT, and then you realize at the three-month mark, oh, there's a little tiny one there, another one there. You can office fulgurate them, you can take them back to the OR if you had to. But in general, a lot of us would try, if we had the ability, to maintain them in the office. But there's a subset of patients that we recognize that will continuously recur. And even though we've done an aggressive TUR and we've tried to meticulously get rid of all the tumors, we repeatedly see on surveillance cystoscopies that they keep recurring and they have multifocal disease. So, I think this is an ideal scenario for these frequent recurs or those who recur, but are really poor candidates to undergo treatment in the operating room with the formal TUR. They're on anticoagulation, they're poor anesthetic risks. And so, this allows you to treat them without taking them to the operating room. But more importantly, it also allows you to treat multifocal tumors, multiple tumors, and reduce the likelihood that they're going to have another recurrence despite their natural history, and despite the fact that they had previously recurred frequently.
Sam Chang: Okay. Now we're going to push it here a little bit. What about if you have one of these patients, and they had lots of tumor, and you gave the six-week, this is a data-free zone, so you've given the six weeks of the thermally reversible hydrogel mitomycin C, you've given it, you look in the bladder, it looks dramatically better, but there's not a CR. Would you consider a repeat treatment?
William Huang: You could definitely consider a repeat treatment. I think that, in those situations, you may want to do a little bit of both, so to speak. So you administer the UGN-102, there's a dramatic treatment response, there may be something incomplete. You can fulgurate it at that time, you can treat it, bring them back in three months again and see if they've recurred. And I think that, in those patients, you can certainly reinduce and then treat them with another course. Again, this is anecdotal, but in my experience, in those patients who had a near-complete response or a partial response that was manageable, they also tend to remain disease-free for a period of time. And those that I have retreated at some point, there was a pretty long interval, certainly nothing like their three to four times a year fulgurating their tumors.
Sam Chang: Yeah. I mean, clearly I think the biology of these quickly recurring, kind of multifocal, honestly, probably they've got multiple tumors just under the surface that we haven't appreciated that we can't treat, that pop up. I mean, these are the ones where you can see treating the entire bladder in a sequential manner for a longer period of time with each medication is going to be much more likely to be successful. So, well, Bill, thank you so much for your knowledge and your insight. It's real-world data regarding, hey, you're going to have different patients who have different risk scores. The vast majority do respond. And I think the key, again, is if they do respond, boy, the majority have a long duration response, just as your poster elicited. And so, we look forward to, as you gain more and more kind of experience outside of the clinical trial in the real world, look forward to touch base with you again to pass on any pearls that you have.
William Huang: Great. Well, thanks for spending the time with me. Appreciate it.