Abhishek Srivastava: Thank you, Dr. Kamat. Great honor to talk to you one-on-one about our UTOPIA trial.
Ashish Kamat: So, the phase three trial of UGN-103, of course, the intravesical mitomycin reverse thermal hydrogel, is being looked at for the treatment of recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer. And I specified there that it's low-grade because I think that's excellent. We talk about intermediate risk, high risk, different categories, but this is specifically for the clinical indication which we all think about low-grade intermediate-risk non-muscle-invasive bladder cancer. So, really looking forward to what you have to share with us.
Abhishek Srivastava: Awesome. Thank you. You're absolutely right, Dr. Kamat. And I know I've looked at your papers specifying and separating low-grade from high-grade cancers. They're completely different risk profile. This is recurrent low-grade which comes at an intermediate-risk non-muscle-invasive bladder cancer.
So, this was a phase three trial of UGN-103 for low-grade intermediate-risk NMIBC. As we all know, UGN-102, which is also known as ZUSDURI™, was a intravesical mitomycin reverse thermal gel. It's the only FDA-approved treatment for recurrent low-grade intermediate-risk NMIBC. And UGN-102, or ZUSDURI™, again, demonstrated 80% complete response rate at three months after treatment initiation and the ENVISION trial. And there was 82% probability of remaining in response at 12 months, and recently 24-month data was presented at AUA which showed 72% complete response rate at 24-month or durability of response.
UGN-103 is, again, a mitomycin and sterile hydrogel, which is a reformulation of the mitomycin lyophilized powder. It simplifies the reconstitution procedure and uses a novel solvent system which improves the solubility and reduces the lyophilization time from 20 days to three days. So, the potential benefit is higher drug availability per vial and faster production time which provides potential for improved access. It basically builds on the platform that ZUSDURI was approved on. Interestingly, FDA required for submission of new drug application. They required UGN-103 to show similar or comparable response rate at three months and similar durability of response. So, this trial was based on that request for new drug application by FDA.
UTOPIA trial. Again, phase three, single-arm, multicenter trial. The primary endpoint was to evaluate the tumor ablative effects of UGN-103, which is a reformulation of UGN-102 in patients with low-grade intermediate risk NMIBC. Secondary endpoints we were looking at was evaluation of durability of response, safety, and tolerability. This trial, 99 patients were enrolled across 30 sites in Europe and US. And it's still ongoing in the follow-up phase. The treatment phase has already finished, and we presented the result at ASCO for the three-month data. And 97% of the patient received all six instillations. The complete response rate was 77.8% at three months in the intention-to-treat population which is 99. The three-month response rate of UTOPIA was consistent with the finding observed following treatment with ... This is during the ENVISION trial. So, similar data.
The last point was not presented at ASCO, but there was a press release at AUA which showed that the six-month durability of response was 94.5% in the patients who responded initially by Kaplan-Meier estimates. And again, the trial was ongoing. So, similar results so far.
The safety and tolerability ... The treatment-related adverse events were minimal. Even though 59% of the patients had some side effects, they were all similar to any intravesical treatment, very minimal Grade 3 or higher adverse events, so most were mild to moderate in severity and were resolved or resolving. And a no-treatment adverse effect led to discontinuation or death. The discontinuation of treatment was reported in 3% of the patients.
And as I was saying, most of the side effects were dysuria, fatigue, pollakiuria, UTI, and hematuria.
So, the take-home message from this trial so far, based on three month and the press release of six-month data, has been that it has shown similar efficacy and safety consistent with UGN-102. 78% response rate was observed, which was similar to UGN-102 of 80%, and a similar safety profile was observed with low serious adverse events. And these results show further evaluation, which is ongoing, and will report the 12-month data. And the durability of response at six month has been good so far with 94.5% durability at six month.
Ashish Kamat: Great. Thank you so much, Abhi. So, in summary, the UGN-103, at least in the data so far, seems to be replicating what we saw with 102, correct? Any signals at all that there might be anything different side effect-wise? Is it better tolerated? Any difference at all?
Abhishek Srivastava: No difference at all. Based on our experience so far, similar tolerability. There is some data to suggest that it may provide better drug availability per vial with mitomycin, but I don't have the data to share, and that this trial was not meant to evaluate that.
Ashish Kamat: And at least based on the data, because the numbers overlap almost exactly, the better drug availability is not translating into better signal or worse signal or anything of that nature. So, talk to us a little bit about the workflow. Is a new formulation easier from a clinic standpoint?
Or, what's the thought process behind your flow in the clinic? How do you see a difference?
Abhishek Srivastava: Great question. So far, what we have seen, there's not much difference in the reconstitution on the clinic side. It's mainly on the manufacturing side. It makes the availability of drug when the demand is probably higher down there is quicker. And the reconstitution process in the clinic is similar. And so not much different on the clinic side, so I cannot speak to that. But yes, manufacturing process is different, and that's why FDA required this new application.
Ashish Kamat: And of course, anytime you have a repurposing or a repackaging, remanufacturing, of a drug, I think the regulatory bodies, in this case, the FDA, has to do their due diligence, which I think is great because you never know. You don't know if it's going to be the same effect or not. And safeguarding patients I think is aim number one, so that's certainly understandable that they would require it. It's also encouraging that clinically we don't expect there to be a difference, and there wasn't a difference. So, I think that's great.
Moving forward, any insight into where this is headed, what the timeline is, from a regulatory perspective?
Abhishek Srivastava: The application will be submitted in Q3 of 2026 and hopefully with approval next year by Q2.
Ashish Kamat: Excellent. Always great for our patients to have more options. And this is wonderful. Thank you so much, Dr. Srivastava, for taking the time. I enjoyed chatting with you.
Abhishek Srivastava: Thank you, Dr. Kamat. Really appreciate you inviting me.