An Innovative Treatment Giving New Hope to Bladder Cancer Patients

November 20, 2025

Transcript

Voice over:

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs:

Hi, I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for by and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model year neobladder, and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, producers of this podcast.

Today is the latest in the series of podcasts that we’ll be doing in observance of BCAN’s 20th anniversary, which we’re celebrating all throughout 2025. In these podcasts, we highlight the commitment of BCAN’s pharmaceutical company partners to creating better today’s and more tomorrows for bladder cancer patients and families. Today we’re featuring Johnson & Johnson as the November 2025 partner in progress. While we’ll be talking about Johnson & Johnson therapies, including INLEXZO, which has the generic name, gemcitabine intravesical system, it’s important to remember that different treatments have different results in patients and your results may vary.

I’m pleased to welcome tonight’s guest, Dr. Sia Daneshmand. Dr. Daneshmand is Professor of Urology and Medicine with clinical scholar designation and director of urologic oncology, as well as the urologic oncology SUO fellowship director at the University of Southern California, USC, in Los Angeles. He serves on the AUA guidelines panel for non-muscle invasive bladder cancer, chair of the bladder section of the SUO Clinical Trials Consortium, secretary of the Western section of the AUA, and chair of the local Bladder Cancer Committee at SWOG. He has led over a dozen clinical trials in bladder cancer and has been designated one of America’s top cancer doctors for the past 13 years. And he is also a member of the BCAN Scientific Advisory Board. Note Dr. Daneshmand and I both have consulting agreements with Johnson & Johnson unrelated to this podcast and its topic. Dr. Daneshmand, welcome.

Dr. Sia Daneshmand:

Thank you, Rick. It’s a pleasure to speak with you today about bladder of cancer and new therapies.

Rick Bangs:

I’m excited. So we’re going to focus today on what I would describe as a unique bladder cancer treatment. It’s from Johnson & Johnson, and it’s their newly FDA-approved gemcitabine intravesical system which I’ve already said is called INLEXZO. And you were the principal investigator on one of the clinical trials for INLEXZO, so I’m hoping you can help our listeners understand what a principal investigator does because it’s an important role.

Dr. Sia Daneshmand:

Well, thank you, Rick. So with clinical trials, these are sponsored, some of the larger trials are sponsored by large pharmaceutical companies and they identify experts around, if it’s a local trial, around the country. And if it’s a global trial, around the world, they’ll have a principal investigator who’s responsible sort for the overall conduct of this study, if you will. And obviously, they have a lot of help. We have a lot of help, but questions arise as patients enroll in these trials, whether they’re eligible or not. And as the trial progresses, we have conversations about what’s going on. And of course, when it comes to the final presentation of the data and the writing of the manuscript and things like that, we’re very much involved. So as principal investigator, we sort of serve in that primary role of partnering with the big pharmaceutical company to relay the message to the public through scientific presentations and publications.

Rick Bangs:

Okay, excellent. All right, so this Johnson & Johnson trial used this unique delivery mechanism from gemcitabine. And gemcitabine is probably familiar to our listeners. It’s a chemotherapy drug. It’s been used for years. It’s used both intravenously and intravesically. And when we do the intravesical or when you guys do the intravesical, it’s installed using a catheter. So based on FDA approval and guidelines, what patients would get an INLEXZO treatment?

Dr. Sia Daneshmand:

So this trial specifically was in patients who had received previous BCG and they were deemed BCG-unresponsive and had high risk non-muscle invasive bladder cancer. So the FDA had mandated for trial eligibility, you have to have not responded to the induction as well as a maintenance course of BCG with the last course being within the last year. So, generally, basically you’re getting at least two courses, if you will, of BCG and you haven’t responded. That’s the patient population. So it’s a very high-risk population. These are patients who generally can progress to muscle invasive disease if not treated appropriately. And so this was one of the few trials that was in this patient population and this was a global trial.

And like you said, it was using a medicine that we’re all familiar with, and many patients were familiar with, gemcitabine, which we’ve used for many, many years as the aqueous solution, which means just the liquid form of it in the bladder. Much like BCG, we generally would put it in the bladder for one hour and then release it via the catheter. So it was sort of exactly like BCG. However, it really wasn’t very effective when used in that way. Whereas the IV form of gemcitabine is what’s used for metastatic bladder cancer, for locally advanced muscle-invasive bladder cancer. And that does work quite well actually for patients. So it is an active drug, but for whatever reason, when you put it in liquid form and put it in the bladder for one hour, it really wasn’t working very well. And prior trials had demonstrated this, one done by Isla Skinner while she was at USC, in this very similar patient population showing about a 20% response rate at one year.

Rick Bangs:

So patients when they would talk to their urologist would understand that something that looks like a pretzel is going to be installed in their bladder. And so could you talk about how does that happen and how is the gemcitabine actually delivered from this device?

Dr. Sia Daneshmand:

Yeah, good question. So this delivery system is basically placed in the bladder through a catheter. Again, something unfortunately patients are very familiar with-

Rick Bangs:

Yes, we are.

Dr. Sia Daneshmand:

… by the time they’ve not responded to BCG for several, so they’ve had at least nine installations and of course the TURBT and all that. However, this is a small specialized catheter, it’s hollow inside, and once we put it in the bladder through the hollow end of it, we are unraveling what you call the pretzel, which is what the enduring term was for this delivery system for a while. So it unravels, it’s got a little wire inside that makes it into the pretzel shape. So we unravel it, we push it through the catheter into the bladder. And as it enters the bladder, it will regain its pretzel shape and sort of start floating in the bladder. Now, inside this pretzel, now people ask, “How big is it?” And of course we show the patients, but for the listeners it’s the size of about two US quarters put side by side, so it’s pretty small and it’s very thin. It’s not like a block I’m just-

Rick Bangs:

It’s not a solid thing.

Dr. Sia Daneshmand:

It’s not a solid thing. Exactly. So inside this system is the gemcitabine pellets, if you will. They’re inside and it has these micropores inside, and as the urine enters this pretzel device, the gemcitabine is dissolved in the urine over the next week to two weeks. So it’s a slow sustained release of the medication. And studies have shown that when it’s a slow sustained release, that the drug is present in the deeper layers of the bladder for days after the installation of this. As opposed to the liquid solution, when we put it in and take it out after several hours, it’s done. There’s no more penetration of the drug into the deeper layers. So it’s really that sustained release that has led to these excellent results, which I’m sure we’ll discuss in a bit. The more the cancer cells have contact with a cytotoxic agent or something that’s killing the cancer cells, the better their response rates are.

Rick Bangs:

Okay, so it almost sounds like it’s smothering the cancer cells.

Dr. Sia Daneshmand:

That’s a good way to put it. Yeah.

Rick Bangs:

Yeah, that’s great. Okay. So, now, are there other similar delivery mechanisms used in other cancers? The bladder is kind of unique, like it or not as patients, it’s accessible, you can put this device in. And as you pointed out, which is such a relief to me, it unravels, right?

Dr. Sia Daneshmand:

Right.

Rick Bangs:

So that part’s comforting, but are there similar things that you can use in other cancers?

Dr. Sia Daneshmand:

Good question. And as far as I know, this is the first in class, which means the first in class of the sustained delivery. I know my wife’s an ophthalmologist and they talk about sustained delivery, but that’s in the form of eye drops and the vehicle and talk about accessible. The eye is very accessible, but they talk about delivery systems there, but it’s mostly in eye drops. But as far as I know, there’s no other organ in the body that’s so accessible where we drop something in and have it release a type of medication for a period of time. So what’s exciting is it really opens up the avenue for multiple other drugs to be placed in the bladder. And of course, that’s being worked on right now.

Rick Bangs:

Yeah, because there’s always talk about all these agents that work in the lab, but they don’t work in patients, right?

Dr. Sia Daneshmand:

Right, exactly.

Rick Bangs:

And so this concept of different kinds of delivery is kind of intriguing because there are agents that might actually work this way or something different on the delivery side. All right, so now I’m one of your patients and what are you going to tell me about the side effects?

Dr. Sia Daneshmand:

That’s a very important obviously aspect of any treatment we prescribe for patients. So, first of all, I would talk about the results that this is highly efficacious and that 82% in the trial, 82% of the patients had responded at some point during their journey. And so we know this is working. Now, some patients end up having recurrences obviously as time goes. So when we looked at this trial at any time there was 82% of the patients who had responded, but as you went to 12 months came down to about half of the patients who continued to have a response. Still, one of the highest response rates we’ve seen for any new agents. So I usually start with that because I think that’s the most important sort of clinical endpoint for patients is, “Does this work? Is it worth going through this?” So, yeah, it is highly efficacious.

And then the side effects are it’s very, very tolerable. It’s not quite like a stent. Some patients have had a stent before and I always tell them, “Look, it’s floating in the bladder. It’s not sitting in one place, and therefore the patients are not experiencing sort of this local irritation.” So for the most part, patients tolerated this extremely well. There were very few adverse events we call them, or side effects, and we grade these things. So most of them are grade one through five, five is very bad. So there were no grade fours or fives. Very, very few patients had grade three. So most of them were grade one and two things. Patients are very familiar with the burning with urination or dysuria as we call it, the urinary frequency urgency, things like that, that again, because they have had BCG in the past, they’re very used to.

Rick Bangs:

Right. Transient too, right?

Dr. Sia Daneshmand:

Exactly. Yeah, these are very transient and we can help with medications that ameliorate the symptoms, things like anticholinergics and other analgesics in the bladder and the urethra, so we can help with some of the side effect profile. And then the other important point is how many patients were unable to tolerate this and said, “Okay, that’s enough. I want this removed.” And it was very few, it was less than 5% of the patients who discontinued treatments because of side effects. Actually, in the trial, there were only four patients out of the 82 that were assessed. So very well tolerated. And overall, very few had serious adverse events or there were a handful of patients that had sort of little bit more serious either urinary tract infection or urinary frequency or urgency of bladder pain and things like that. So, overall, I think patients are used to these types of side effects, but most of them tolerated pretty well.

Rick Bangs:

Great. All right. So now we’ve talked about gemcitabine and cisplatin. We talk about that fairly frequently. That’s a very common treatment for many bladder cancer patients used before radical cystectomy. So an obvious question would be, okay, this is just gemcitabine, could you use this kind of mechanism to deliver both gemcitabine and cisplatin?

Dr. Sia Daneshmand:

Yeah, good question. So, generally don’t use cisplatin as a solution or as a medication in the bladder itself, cisplatin is an IV form of medication, actually doesn’t come in a solution form. Now, can you use this potentially as a combination therapy either as two pretzels or have it half-and-half and things like that? The answer is some clever bioengineers can probably do something like that. Cisplatin, as far as I understand, in the bladder is not very well tolerated. So the focus right now is on other drugs. And we currently have a global trial looking at another drug called Erdafitinib in this very similar drug delivery system. And that’s under clinical trials with some very positive results in patients who have low-grade, recurrent low-grade tumors, or the intermediate-risk non-muscle invasive bladder cancer patient population.

Rick Bangs:

Okay. All right. So I’m curious more about that patient experience. So are you putting me under anesthesia for example? And you talked about how big it is and that it unravels. Is it uncomfortable? Because before it unravels, you still have to get it in my bladder. And how many of these are you going to be installing over time?

Dr. Sia Daneshmand:

Yeah, good question. Okay, so the installation process itself is almost no different than getting BCG. So you place a catheter in the bladder and this device goes through the catheter. And once it reaches the bladder, you’re not feeling anything actually other than the catheter. So the process is exactly the same as delivery of any other medication. Once it’s inside, the bladder is not a hollow organ, it has urine in it and it’s floating around. So the device starts floating around and you don’t feel it at all because it’s not sitting in one area. It’s a very, very small light device, but it does require removal obviously. So it’s being placed once every three weeks. So you place it and then patient comes back three weeks later for removal. Removal means cystoscopy, which is exactly the same size. The scope is the same size as a catheter as well, 16 French.

We put it in the bladder. We have specialized graspers and we grab one end of it and we pull it out. Again, pretty well tolerated. That takes literally minutes for all the urologists who do any kind of procedures. They know that removing any device from the bladder or stent, which is the most common thing we do, is very simple and straightforward. So the patient’s doing this once every three weeks for six months, so the first 24 weeks is every three weeks. So we have eight installations and removals, then they have it quarterly after that, so it’s once every three months and they go on this maintenance phase for up to two years. That’s how the trial was designed, that’s how the FDA approved the drug, and that’s how we’re going to be using it until we get more data to the contrary.

Rick Bangs:

So installation sounds like it’s going to be relatively quick. Am I under anesthesia, can I drive home?

Dr. Sia Daneshmand:

You can absolutely drive home. No, you’re not under anesthesia because it’s the same as BCG. It’s just a catheter-based placement. So we do use a lidocaine gel of course, but for all the patients who have had BCG, of course you’ve had BCG before by the time you get to this drug, then we tell them, “Look, it’s the same process. We’re going to put something in your bladder. Instead of a solution, we’re going to drop this drug-releasing system in the bladder.”

Rick Bangs:

Okay. All right. So now you put it in my bladder and it sounds like it’s floating around, but at any point would I feel this? And if I would feel it, what might trigger it? I mean, things like urination and physical activity or sexual activity, those are things that I would want to know whether or not those are going to trigger any sensation from the device.

Dr. Sia Daneshmand:

So, I learned, I started using this in 2016 when we were doing the phase one trials and had a lot of experience before it got to this phase three trial, I already knew it was very well tolerated. Now, there’s some patients who have some burning associated with the medication, not so much the device itself. And I learned this because during the first few days they weren’t having any symptoms and then they started having this burning. And then once we removed the device or as the drug delivered entirely into the bladder, then their symptoms subsided. We learned that some patients are a little bit sensitive to the gemcitabine in the bladder. It’s a little bit acidic, and so some patients are having these cystitis or pain or some burning associated with urination. So that was one of the most common sort of grade one, grade two adverse events was this dysuria that was seen in about a third of the patients complain of some burning with urination.

And for that we recommend alkalinizing the urine. Again, gemcitabine is a little bit acidic, and so I don’t think it’s the device itself that was causing the issue. I think it’s the medication itself that’s being placed. And because I’m involved in this other trial with this other drug, I’m learning that this Erdafitinib drug, for instance, is actually even better tolerated and they don’t get as much of the burning. So we’re learning and we’re trying to prevent these side effects as we go.

Rick Bangs:

Okay. So now how are you going to make my bladder, I think you said alkaline, so you said you’re offsetting the acidity.

Dr. Sia Daneshmand:

Exactly.

Rick Bangs:

So are you installing something else? Am I taking a pill? How are you doing that?

Dr. Sia Daneshmand:

You’re just taking a pill, a baking soda pill.

Rick Bangs:

Baking soda?

Dr. Sia Daneshmand:

Yeah, sodium bicarbonate. So it’s very easy. We give it for various indications, but that’s one of them. So, yeah.

Rick Bangs:

Okay. And so now you mentioned Erdafitinib. Are there other trials within INLEXZO and varying agents. What’s in the pipeline currently relative to this kind of intravesical system?

Dr. Sia Daneshmand:

Well, I can tell you that there were five SunRISE trials. One, they’re all the same device, same drug delivery system that’s being tested in various different settings. So, SunRISE-1, for instance, was this study obviously for BCG non-unresponsive disease state. But they thought, “Well, why don’t we just test it out against BCG and see whether it performs as well or even better than BCG itself?” So there was a global trial, the SunRISE-3 trial, that went head-to-head with BCG and they were using the INLEXZO along with cetrelimab, which is one of those new immunotherapy drugs that’s given IV. So it’s a comparison of those two. And then the SunRISE-2, and the results will come out very soon at our national meeting that I think I’ll be presenting, SunRISE-2 is going head-to-head with chemo and radiation therapy for muscle-invasive bladder cancer. Again, given along with a checkpoint inhibitor.

So it’s being tested in multiple different settings and SunRISE-4 was before a radical cystectomy as neoadjuvant therapy to see what its activity is not just in non-muscle-invasive bladder cancer, but also in muscle-invasive bladder cancer, because we know that the gem is actually penetrating deeper layers. But your question was also, “What else is in the pipeline?” I mentioned Erdafitinib. That is a highly, highly effective drug against the tumors that harbor a mutation called the FGFR3 mutation. And so it is one of those targeted therapies that’s not well tolerated orally. It is efficacious and it is FDA approved for metastatic disease in patients who harbor this mutation for metastatic bladder cancer. But they thought, “Well, why don’t we put it in this pretzel device and see if it works in these patients who have low-grade disease?” And lo and behold, the early results are really spectacular. We’re seeing responses.

So, Erdafitinib would be next, and I know the company’s working on other medications, let’s say, in this drug delivery system to come in the future. So I think this is the very beginning of an exciting era of new delivery devices and delivery drugs into the bladder.

Rick Bangs:

Excellent, excellent. So do you happen to know how Johnson & Johnson might’ve used patient partners research advocates in the design and delivery of their clinical trials or specific to your clinical trial?

Dr. Sia Daneshmand:

Good question. I think, as you know, and of course you’re a major contributor to our cooperative group trials at SWOG, I think these have a little bit less patient engagement in the design of the trial. They certainly engage with the surgeon scientists and clinicians to come up with these various trials. We have advisory boards that we meet at least on a quarterly basis and discuss the next set of studies and what everyone thinks. And these are global experts, so it’s really refreshing to know that we’re involved in the trial design. But I think we can probably use some patient input as well into the very design from the beginning.

I certainly know that they have engaged patients. In fact, just yesterday, I think, a New York Times advertisement came out with one of my patients, and that’s out there somewhere, you can look up. And they did a really wonderful video of the patient’s experience both in this trial and with this treatment. So it’s a real beautiful sort of story journey of this patient who was BCG unresponsive and was told he needs a cystectomy and they follow his life and how he chose this trial and how he’s been successful in keeping his bladder. So, yeah, bottom line, I think there are lots of patient engagements, but not as much as cooperative groups. More patients get involved in the beginning phases of the trial design.

Rick Bangs:

Okay. All right. Any final thoughts?

Dr. Sia Daneshmand:

Final thoughts are honestly, I think it’s an exciting time for us and for patients hopefully. We have new therapies that are available to us that are ready to use. And this just got approved in September 19th, FDA-approved, and literally what’s great about J&J is they have the resources to get this to us in our hands as soon as possible, so literally a week after I was able to place one of these drug delivery systems in one of my patients. So that’s exciting that we have one more drug in our armamentarium and one more treatment option, and there’s more to come. There are lots of exciting trials right now underway, and this is exactly what we needed. We had been talking about it for so long, we just didn’t have anything as you know, either this works or if it doesn’t, your bladder is coming out. And now we’re talking about sequencing of medications and sequencing of different treatments. So really exciting times. I’m super excited and lucky to be in this field and in this time to be able to contribute a little bit to the progress here.

Rick Bangs:

All right. So we’ll stay tuned and invite you back when we’ve got more to talk about. That’s great.

Dr. Sia Daneshmand:

Thank you, Rick. Thanks. It’s always a pleasure.

Rick Bangs:

All right. Dr. Daneshmand, I want to thank you for sharing insights on Johnson & Johnson’s INLEXZO and for your part in creating better today’s and more tomorrows for bladder cancer patients and families.

Dr. Sia Daneshmand:

Thank you so much.

Rick Bangs:

If you’d more information on bladder cancer, please visit the BCAN website, www.bcan.org. In case people wanted to get in touch with you, could you share a Twitter handle or some other contact information?

Dr. Sia Daneshmand:

Sure. Yeah, Twitter would probably be a good place. It’d be @SiaDaneshmand, my first name and last name put together.

Rick Bangs:

Okay. We’ll look for you there. Just a reminder, if you’d more information on bladder cancer, you can contact the Bladder Cancer Advocacy Network at (1888) 901-2226. That’s all the time we have today. Be sure to like, comment, and subscribe to this podcast so we have your feedback. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Daneshmand.

Dr. Sia Daneshmand:

Thank you.

Voice over:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network, or BCAN. BCAN works to increase public awareness about bladder cancer, advanced bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.