Transcript of How Patients Can Navigate the BCG Shortage with Dr. Robert Svatek

December 30, 2021

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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. This podcast is sponsored by Merck and Bristol Myers Squibb. I’m excited to have Dr. Robert Svatek, Professor and Chair of Urology at the University of Texas Health San Antonio as my guest today. His practice is devoted to the care of bladder cancer patients. He provides state-of-the art surgical options, including robot assisted and open approaches, as well as all available urinary diversion options. Dr. Svatek is actively involved in clinical trials for bladder cancer, including one on the Japanese strain of BCG and runs an NIH funded cancer immunology lab. Dr. Svatek, I’m so pleased to have you on our podcast to talk about BCG and how patients can navigate the BCG shortage.

Dr. Robert Svatek:

Rick, it’s a pleasure to be here.

Rick Bangs:

Let’s start with some basics about BCG. Which bladder cancer patients will typically be prescribed BCG treatments?

Dr. Robert Svatek:

So, BCG is utilized for patients that are suffering from non-muscle invasive bladder cancer. And that’s a sophisticated term that really describes a tumor that is superficial in some ways, meaning it hasn’t developed roots to go deep into the bladder muscle. The term superficial is a misnomer though, because some of these tumors can be invasive. They’re just not invasive into the muscle. And, BCG is often given for the superficial tumors that are more likely to recur after they’ve been removed. And so, we often give it for patients that have high grade or high risk features, and those features indicate that they have a fairly high chance of the tumor coming back after it’s been surgically removed.

Rick Bangs:

Okay. And unlike most chemotherapy, BCG is not administered through the veins, right? How is it administered?

Dr. Robert Svatek:

Correct. BCG is given through a very unique route. What we call intravesically, which means that a catheter is placed into the bladder and BCG is instilled through that catheter in a solution of fluid water or saline. And the advantage of that is that we have access to the bladder where we can give a fairly large bolus of BCG in terms of its dosage to facilitate immediate and intimate contact with the bladder mucosa. And so, that’s an intravesical installation.

Rick Bangs:

And what’s a bolus?

Dr. Robert Svatek:

Well, a bolus would be a large dose in a small amount of time.

Rick Bangs:

Okay. So, are there other cancers where you are putting something inside the thing that has the cancer, or is bladder unique?

Dr. Robert Svatek:

It is unique in that way. There are some tumors that have easy access, skin tumors, for example. One of the first experimental uses of BCG was to inject it into a skin tumor. And, there are some tumors where injection therapy is still helpful, but those are not very common.

Rick Bangs:

Yeah, that’s what I thought.

Dr. Robert Svatek:

Yeah.

Rick Bangs:

Okay. And how effective is BCG?

Dr. Robert Svatek:

Extremely effective. For those patients that we were talking about earlier, and we measure effectiveness really two different ways. One way is the ability of the agent to prevent a tumor from coming back. And, BCG can almost decrease the recurrence or relapse by about 50%. And so, over a long period of time, we can reduce recurrences by up to 50% with BCG. And the other way that we look at it is, in some patients that have a tumor that is diffuse in the bladder, it’s also called carcinoma in situ, or CIS, BCG can actually eliminate that tumor. So, it’s used as a treatment to eradicate CIS and it’s highly effective for doing that up to 80% or more of patients with CIS will experience complete eradication of that disease with BCG treatment.

Rick Bangs:

And, the CIS, that’s the flat one that’s on the surface versus the often referred to as broccoli stalks.

Dr. Robert Svatek:

That’s right. If you could imagine two different types of bladder cancer, one is a broccoli or cauliflower configuration. Sometimes it looks like coral reefs bubbling off of the surface. So, that’s a papillary configuration or architecture. And then CIS has a different architecture, which is flat. Often best described as a velvet carpet. So it is slightly raised above the surface, but just a little bit. And it tends to be more spread out, not in just one location, but often will spread to multiple parts of the bladder.

Rick Bangs:

And now, how does something like BCG compare to some of these chemo therapies that are done through the intravenous? How does BCG stack up?

Dr. Robert Svatek:

So, BCG has been compared against chemotherapy in multiple different trials and often those trials are done where they’re both given intravesically. So, they’re both given through the same route, through a catheter placed into the bladder. And, in almost every scenario in every clinical trial that we’ve seen, BCG tends to outperform chemotherapy, and there have been composite analysis of that data, what we call a multi analysis or a systematic review that supports the notion that BCG outperforms intravesical chemotherapy. Now with regards to chemotherapy given by other routes, let’s say intravenous route for example, we’ve not done head-to-head trials in that way. And that’s largely because we don’t use intravenous chemotherapy for this particular disease site. It is unlikely to be completely effective and it’s the toxicity of intravenous chemotherapy may outweigh any potential benefit.

Rick Bangs:

Okay. So speaking of side effects, what are some of the common side effects of BCG? And can they be minimized?

Dr. Robert Svatek:

So BCG, most of the side effects are local. And what I mean by local is the area where the BCG is given. And so, the BCG is a bacteria. It is a real live growing organism. Now it’s attenuated, it’s weakened so that it’s not supposed to cause infection, but it is a live organism. And when you put it into the bladder, your immune system, your body thinks that it has an infection in so many ways. And so, the immune system reacts to it. And in fact, that’s the reason by which it’s thought to be effective is by stimulating the immune system. But as a response to that immune reaction patients will experience local symptoms, such as urinary frequency, having to go to the restroom more frequent or more urgent. Some patients experience burning with urination. There are some other symptoms that are more global or more systemic, low grade fever, general weakness, or malaise. The vast majority of those symptoms, of all these symptoms are transient and usually resolved by 48 hours after the administration.

Rick Bangs:

And, just a question about the severity of side effects. So, if I have severe side effects, does that mean that the BCG is working better than if I didn’t have side effects at all? Or they were minimal?

Dr. Robert Svatek:

It’s a good question, Rick. There have been some reports that suggest that patients that have some reaction, let’s say low grade fever or malaise or things, are more likely to respond to BCG. And there’s a correlation between those side effects and efficacy, but those are soft correlations. It’s not a hard and fast rule. As a practitioner, I generally like to hear that patients have some response or some reaction, whereas those that have completely no reactivity to the drug, I sometimes worry that there may not be effective, but that said, there are many patients that have very limited responses that do well, and there are many patients that can receive multiple treatments of BCG without serious side effects and have good response. So it’s not a hard and fast rule, there may be something to it, but it’s not completely well worked out.

Rick Bangs:

Okay. And, you talked about BCG being bacteria of sorts. And so, I believe it’s something that is called a biologic, which is a little different from a drug. So, what is that?

Dr. Robert Svatek:

So, a biologic, BCG is a bacteria. It is grown in a laboratory and just like a bacterial culture can be grown in a Petri dish. And then it’s quantified and measured and placed into a dormant formulation called lyophilization, which basically is a way to keep it packaged and a means to that disseminated or transfer it. But then once we put it into a solution, it is then reactivated and awakened, if you will, for treatment. And that’s different than let’s say a molecule that is not a biologic source. And so, this is a truly a biologic formulation treatment.

Rick Bangs:

So, it’s something that we grow rather than something we make in a sense.

Dr. Robert Svatek:

That’s a good way to put it, Rick.

Rick Bangs:

All right. So, would there be such a thing as generic BCG?

Dr. Robert Svatek:

So, I think that when we talk about generic, I think that implies initially a compound. It’s often more expensive, a treatment is more expensive because the generic’s not available. And after so many years, a generic becomes available. BCG has been out since the late eighties. So, we are definitely into the generic phase of it.

Rick Bangs:

Okay. But, not all BCG is alike. So there are things called strains, and I believe there are different strains across the world. So, tell us a little bit about that.

Dr. Robert Svatek:

I think the history of BCG is important in that discussion. So, BCG was originally developed, not for bladder cancer, but for vaccination against tuberculosis. So this is back at the turn of the century in the 1900s and tuberculosis was rampant. Effective treatment at that time was not available. And so, the vaccine was developed in France and once it was found to be effective, it was distributed throughout the world to different locations and different laboratories would then grow the organism. And what happened was that it changed over time so that you have different strains that developed all from that original strain in Paris, but they accumulated different genetic mutations, which then translated into differences in terms of their protein expression. Now, the genetic changes are now stabilized because in the 1960s, a seed lot system was adopted, which basically means that moving forward, we would use the original seed lot as we grow them.

Dr. Robert Svatek:

So, the genetic changes have stopped, but there are numerous different strains that have developed from that mass dissemination. Now, whether or not these strains… Now, clearly there’s some genetic differences. And there are differences in the protein that these strains make, but whether or not these strains differ in terms of their effectiveness in preventing tuberculosis or in their effectiveness of treating bladder cancer is unknown.

Rick Bangs:

So, it almost sounds like back in the early 1900s, there’s the great, great grandparent and then we had some children or grandchildren, whatever, and they’re not quite the same, but they’re similar, but now we’re maintaining some consistency. Maybe we’re cloning something and keeping it the same, rather than allowing more children and grandchildren. Is that right?

Dr. Robert Svatek:

Yeah. I think that’s a great way to put it. These different grandchildren, they differ genetically and biologically, but now we have a way to go back to the original seed lots from the 1960s so that we’ve stopped additional changing or additional, more grandchildren developing. So, we were using those original lots from the 1960s. So, they do differ, but the changes of these strains has now been stopped so that they are stabilized now.

Rick Bangs:

So, I’m a little fascinated because this started out with tuberculosis. So, how and why does it find its way to bladder cancer?

Dr. Robert Svatek:

That’s the beauty of this thing. So, from far back, if you trace back immunology, there’s been observations that people that experience an infection can spontaneously have resolution of their cancer. And this was an observation made thousands of years ago and then subsequently it was employed as the first kind of cancer immunotherapy. And what I mean is, let’s say that you have a patient with some tumor. That they’re suffering from a tumor. It was demonstrated that you could actually induce an infection in that patient and you would get shrinkage of their tumor. And so, this was even taken to the extent that a treatment was developed that included pus or bacteria that was utilized to treat patients that were suffering from cancer. That was early part of this century or last century. And it never really took off. It worked, but it wasn’t adopted as standard of care.

Dr. Robert Svatek:

And it wasn’t until the rejuvenation of the cancer immunotherapy platform that we started having other ideas in terms of utilizing cancer immunotherapy and BCG is one of those. So, BCG is a bacteria and there was observations that people that developed tuberculosis would have resolution of their cancer and BCG along with other bacterias, started to be utilized in the laboratory setting to see if they could induce tumor remissions or tumor regression. And, it turns out that it did. And ultimately this led to a clinical trial where BCG was instilled into the bladder in patients with bladder cancer. One of the critical observations made from the laboratory was that for BCG to work, you needed to have close contact with the tumor.

Dr. Robert Svatek:

You needed to be able to use a really high dose of BCG. And, it just so happens that the bladder is one environment where you can fulfill those two requirements because you do have the ability to get directly into the bladder with a catheter, and it’s safe enough to administer a very high volume of the organism. And so for that reason, bladder was a target organ for this type of treatment. And so, the clinical trials demonstrated that it did work. And so, now fast forwards today, it is now standard practice for the treatment of this high grade, non-muscle invasive bladder cancer.

Rick Bangs:

Bladder cancer was an early adopter of immunotherapy, even though we think of it as having been stagnant for so long and so far behind, we were actually in the forefront.

Dr. Robert Svatek:

Yeah. And, you’re right. And, urologists were treating patients with cancer immunotherapy long before we had other breakthrough cancer immunotherapies available, which we now have today. Thank goodness. But we’ve been utilizing this cancer immunotherapy for decades. And so, it was, you’re right, it was one of the early successful stories of cancer immunotherapy.

Rick Bangs:

So, as we made this journey from tuberculosis to cancer and specifically bladder cancer, because you said it needed to have contact and it needed to be in high dose, how did we determine what the right dose was for somebody who was a bladder cancer patient to get BCG?

Dr. Robert Svatek:

Well, that’s a really good question. The early trials that were conducted were largely just… It was not a whole lot of effort put into studying different doses. We utilized a high dose and we found that that worked. And so, the subsequent trials were done with that particular dose. It wasn’t until now, basically current day and age, that we’re really looking and asking ourself, “Okay, what dose is appropriate and how much should we give or how much is meaningful?” So we’re working backwards in a way, in terms of figuring out the minimal amount of dosage that we could do to still be effective. There have been a handful of trials that have looked at various doses or various regimens. Currently BCG has given over a three year period, 27 installations if you add them all up and many patients are unable to handle that volume of treatment. So, we have asked the question about, could less be equivalent. And it turns out that in some patients, you don’t need to give three years of treatment. Some patients would do okay with maybe one year of treatment, depending on their risk.

Rick Bangs:

And so, this question of dosing is particularly relevant in this context of continued shortages. So, we’ll come back to that in a second here. So, let’s talk about the challenges of manufacturing BCG. So, even if I’m a pharmaceutical company and I’ve got these wonderful high standards of quality control, could I anticipate getting a predictable and consistent result from my production every time I go into production?

Dr. Robert Svatek:

I think you’re right on in terms of the fact that you’re alluding to the challenges that companies have when manufacturing a biologic, particularly one like BCG, that is a live organism that needs to be grown. It needs to be taken from the freezer from a seed lot and then grown in a sterile environment and then packaged into vials that can be distributed. Any small change to that environment could affect the growth of the organism. And, you can imagine that there must be lots of precautions in place and standardizations in order for this to be done without any risk of contamination because these are going to ultimately go into patients that we have to have exceptionally sterile environments and manufacturing conditions that will be safe. And so, you bet, there have been challenges to production. As a result of that, we have suffered from shortages that you mentioned earlier.

Rick Bangs:

It seems like there’s an obvious conflict between growing something and a sterile environment. It seems like those things are conflicting.

Dr. Robert Svatek:

Yeah.

Rick Bangs:

So, we’ve got this third shortage in about a decade. And so, why are we having these shortage and what happened to what was known as the Connaught strain?

Dr. Robert Svatek:

The reason for the shortages are multifactorial, but they have to do with the conditions and the manufacturing problems that we talked about. Also, the ability of one company to provide sufficient BCG for the population. So, before we had two companies that were making BCG, two different strains, one was Merck, which makes BCG TICE, the other company was Sanofi Pasteur, which made the Connaught strain. They were based out of Canada or they are. And, they essentially ceased production of the Connaught strain. And, the details of that are not clear, but ultimately there were some requests made by the FDA to the company for reaching certain standards in order for the production facility to go back online. And the company decided that it was in their best interest to not produce it. So, they ultimately stopped the production of the Connaught strain.

Dr. Robert Svatek:

And so then Merck, which makes TICE was left with basically providing BCG for all of those sites that had been dependent on the Connaught strain. And so, as a result of that, we have had periodic shortages of TICE BCG. And the other component to this, Rick, is that you can’t just take another strain into the U.S. and start producing it. This has to be FDA approved. And so, right now, the only strain that is FDA approved for use in the U.S. is TICE. Connaught is also approved and there’s another strain called Armand-Frappier that is basically not in production anymore, but ultimately you’re going to need to have FDA approval. So even though we have other strains that are utilized in the rest of the world, in Europe and in Asia, those companies can’t just come to the U.S. and sell their product because they don’t have FDA approval.

Rick Bangs:

So, going back to the analogy we used, so those are like cousins and the cousins aren’t approved, but the TICE strain, the Connaught strain and this other one that’s not being manufactured, those are approved in the U.S., but the cousins are being used outside the U.S., but aren’t approved in the U.S.

Dr. Robert Svatek:

That’s right.

Rick Bangs:

Okay. And so, what do we know about Merck’s plans relative to the TICE strain?

Dr. Robert Svatek:

We understand, Merck, I think has done a tremendous job of trying to provide product. You got to realize that this BCG is not particularly profitable to my understanding. It’s a generic therapy, as we talked about earlier. And the profit margin is, from a company’s perspective, not what they would get from a new agent, but that said, they have been able to help provide product and try to help mitigate some of the shortages. They are planning, as I understand it, planning to build another production facility in order to help meet the U.S. needs. But, the details on that, Rick, like, when is it going to happen and how long it will take, I just don’t know.

Rick Bangs:

Right. So, now we’ve got this context on what it is and how it works and the shortages and so forth. So, now let’s get a little bit practical and a little hands on. So, suppose I’m a patient and I can’t get my initial BCG treatment. And initial BCG treatment, and I’ve learned this from you, is commonly referred to as induction. So, now what? So, do I shop around as a patient? Am I shopping around trying to find this? And even if I could find it, could it be transferred into the institution that I want to go to or need to go to, do I have to oversee the transfer? What am I doing as a patient if I can’t get my initial BCG?

Dr. Robert Svatek:

Unfortunately, we deal with this a lot, Rick. So, I think the most important thing is to have a discussion with your urologist as a first step to see, how important is it that you get BCG? Because while there are multiple different types of patients that would benefit from BCG. Some need it more than others. That’s clear. There are certain patients where it’s, there are other options that are suitable. So, one step is to just have a discussion and say, “How critical is it given my disease state and what alternatives are there? For example, intravesical chemotherapy. And, how effective are these alternatives compared to BCG?” And, that would be my first step is to consider what alternatives you have locally.

Dr. Robert Svatek:

I have had patients that have gone or come from other places where they were not able to access BCG and come to us to get BCG. So, there are situations where one facility may have it and another down the road may not. And so, it is sometimes appropriate to ask around, check with another urologist, check with a different facility to see if that may be available. And, it’s good to know that the BCG is the same in terms of its quality, whether you get it in city A or city B, it’s all made from the same manufacturer. And the delivery of BCG is not variable. It’s not going to be better for you if given by this particular facility versus another facility. That’s good. So, in some cases we say, “If you can get it somewhere else great. And if you can can’t, then we look at other options.”

Dr. Robert Svatek:

And there are other options. So, it’s just a matter of what’s the best option for you. And, depending on where you’re at in the disease process. Some of the things that… And maybe we’ll get into this, Rick, I don’t know if you were going to mention… But things that sites are doing to help mitigate the problem, for example, a split dosing. And, say your doctor may be offering you a reduced dose of the drug as a means to provide for more of the patients. And, that may be something that you could discuss as an option for you in this situation.

Rick Bangs:

Yeah. And those were things that early on in the shortage process were very difficult. As a patient, it just seems really, really simple to do the shared dosing, because you’ve already mentioned that you may have to reduce dose anyway. So, why not give somebody the other part, but it’s not so easy because there’s all kinds of laws around how you can bill and what you can bill and so forth, aren’t there?

Dr. Robert Svatek:

If you’re looking at reimbursement for installation of a therapy and then you only give half of that therapy, how do we adjust the reimbursement? If you’re paying for BCG from the supplier and you’re getting reimbursed for it, but you’re splitting it then how does that impact how you get reimbursed for it? Now, this is, in the grand scheme of things, the amount of money that, BCG is relatively inexpensive compared to cancer immunotherapy, generally. So, I have to be honest, part of us, as urologists, feel that this is really shouldn’t be a major issue for reimbursement purposes because it’s just such a small amount compared to cancer immunotherapy costs. But, we want to do it correctly in terms of how it’s supplied and billed. So, it has become a bit of a challenge. The AUA has released some guidelines to urologists on how to manage and how to maintain high quality of care for patients with non muscle invasive bladder cancer under the situation of shortages. And, I think that those are helpful for standardizing our practices.

Rick Bangs:

I think BCAN participated in those along with the other big urology groups. So, it was a consensus view of, this is the best way that we collectively think we can get through this even though it’s not ideal by any stretch of the imagination, this is making the best of a bad situation.

Dr. Robert Svatek:

Exactly.

Rick Bangs:

So, I just want to go back quickly to this idea of transferring. So if I can’t get it at your institution, but I find it at another institution, can it be transferred or do I have to go to the other place or is it going to vary? Sometimes it can be transferred? How does that work?

Dr. Robert Svatek:

It can, we’ve transferred it and there’s nothing illegal about transferring it. It’s just a matter of, is that institution going to want to transfer their…

Rick Bangs:

Right.

Dr. Robert Svatek:

This is a precious stock of therapy. And, if I have a limited amount for my patients, it’s going to be difficult for me to transfer it out to another city. So, we’re in this situation where we’re all advocating for our own patients and that’s a difficulty that we’re in.

Rick Bangs:

Yeah. So now let’s talk, we’re going to ratchet up where I am in the treatment process. So, if I’ve already gotten these initial BCG treatments, which again, you’ve taught me is called induction and I’m now in this next phase, which is called maintenance and I can’t get my maintenance BCG. I’ve had my induction and I’ve had those initial treatments, but I can’t get these maintenance treatments. And so now what? What do I do as a patient in that case?

Dr. Robert Svatek:

Well, my first thing is to say, “Let me provide you with some reassurance.” One of the guidelines that we decided on was that in the event that there’s a BCG supply shortage, that maintenance therapy should not be given and that we would prioritize BCG for induction treatment. And the reason that that decision was made is because we feel that that initial treatment, that induction period, is the most critical. And so, my first thing is to say, “Hey, it’s great that you’re able to get to the induction period.” And so, it’s just to provide some reassurance. Now, again, depending on the high risk features that you have, I might recommend an alternative to maintenance BCG, such as intravesical chemotherapy with things such as gemcitabine, docetaxel, epirubicin, mitomycin, valrubicin, et cetera. These may be used sequentially or in combination as alternative maintenance regimens. And, that may be something that you would be interested in and it would be in consultation with the urologist.

Rick Bangs:

And, these are instilled in the bladder through a catheter or these…

Dr. Robert Svatek:

Yes. Given the same route through a catheter intravesically through a catheter into the bladder.

Rick Bangs:

Okay. And now, from a supply situation point of view, do you know if urban settings are having more or less trouble than community more rural settings or is it the problem is a universal, spread evenly, everybody’s suffering consistently?

Dr. Robert Svatek:

Well, I do think we’re all suffering. I’m in a urban setting and I have had shortages, I haven’t studied this Rick, but I do get the sense that the rural areas may be more affected disproportionately than the urban. I say that only because I’ve had many patients from rural areas that are unable to get BCG that have come to me. So, I do think that there may be a disproportionate availability, but I just don’t know that for certain. We haven’t studied it, but it’s just a kind of a gestalt.

Rick Bangs:

Yeah. It seems logical that it’s going to be harder to shop around. So if I’m in an urban setting, it’d be much easier for me to shop around than go from A to B to C if I can’t find it versus a rural setting.

Dr. Robert Svatek:

Right. And the other issue is, how much can you keep…

Rick Bangs:

On hand.

Dr. Robert Svatek:

… On hand. Because it does have a shelf life and it does last quite long. But if you’re in a rural situation where you’re only giving an induction period once a year or once every six months, it doesn’t behoove you to keep large stock supply.

Rick Bangs:

Right. And, my allocation might vary based on how much I’ve historically been doing.

Dr. Robert Svatek:

Exactly.

Rick Bangs:

I don’t know how this particular model works exactly, but I know how in business, how we would normally do a model like this and it’s not necessarily the way… It’s not perfect, but it’s often done that way. So, we talked a little bit about the intravesical alternatives and you hinted it’s in clinical trials. So, talk about alternatives and clinical trials specifically.

Dr. Robert Svatek:

We’re interested in a clinical trial that is comparing two different strains. I have a vested interest in this, as you know, because the promise of that is that if we can demonstrate that an alternative strain is as good as the existing strain, then that’s an opportunity to get an alternative strain into the U.S., which would significantly help the shortage issue. And so, that trial has completed accrual, completed enrollment. The data will take some time for it to mature to determine if it is effective. There are considerations of other trials right now comparing BCG versus combination chemotherapy. Gemcitabine, docetaxel, for example, is a combination that many urologists feel is a good alternative. And so, that’s a trial that is being considered right now. And then there are trials in a different space, which is the space where people have had BCG and their disease has persisted or returned, even though they were treated with BCG and we call this the BCG unresponsive disease characteristic. And so in that setting, there are novel drugs and novel drug combinations that are emerging for those patients.

Rick Bangs:

So full disclosure, I’m the patient advocate at SWOG working with you on this clinical trial, so full disclosure there. And so, that trial is closed to new patients. We’ve already accrued the number of patients that were slotted for this particular trial.

Dr. Robert Svatek:

That’s a good point. That was completed in December of last year, the enrollment.

Rick Bangs:

All right. So, we’re excited to see some results there, but you’re doing something a little different in that trial, not just comparing the strains. So I think it’s probably relevant to have a short little discussion about the third group in the trial.

Dr. Robert Svatek:

That trial was also looking at the ability of a vaccine given into the shoulder or intradermal is what we call it, just underneath the surface of the skin. Given before we put the BCG into the bladder. And so, the idea is that by giving a vaccine, we can prime the immune system to recognize BCG proteins, to stimulate the T-cells, the immune cells so that when we do put the BCG into the bladder, that the response is more robust and the effectiveness of the BCG is better. And so that is the third arm is a group of patients that will get an intradermal vaccine given 21 days prior to the installation of BCG in the bladder. And we’re hoping, or we’re proposing that that population experiences a 25% increase in effectiveness of BCG in terms of preventing relapse of bladder cancer.

Rick Bangs:

And, I suspect this resonates more with patients in a COVID world where there’s all this talk about how long between the first Pfizer dose and the second Pfizer dose and boosters and Moderna, the same thing and J&J, so this issue of priming the immune system and then coming back and hitting it up again, and how long that should be, I think much more understandable than it would’ve been pre COVID.

Dr. Robert Svatek:

Absolutely. People are a lot more informed on immunology nowadays.

Rick Bangs:

Right. Sadly.

Dr. Robert Svatek:

That’s true.

Rick Bangs:

It’s both good and bad.

Dr. Robert Svatek:

Yeah.

Rick Bangs:

Any other viable options being pursued in the U.S. or we can look outside the U.S. as well. Anything else that’s hot and interesting?

Dr. Robert Svatek:

There are a lot of really neat ideas and concepts being developed on very early levels in the laboratory as well as more later, toward the clinic. And, just as an example, there are methods to modify the BCG organism. So, we create what’s called a recombinant BCG, or it’s genetically modified, and that’s appealing for a variety of reasons. For example, if you could modify BCG to improve its effectiveness or decrease it’s side effect profile, that would be an advantage. And so these BCG recombinant strains, I think, is something that holds promise for the future. Also, combining BCG with new agents or old agents that have been used in a new way. A lot of work is being done in that area. I don’t see BCG going away anytime soon, next decade or two decades. But I do think sometime in the distant future, we’re going to have a better alternative. And, I think some of the work being done in laboratories is working toward that end.

Rick Bangs:

We’re so lucky in so many ways to have something like BCG, which is pretty effective, generally tolerable and relatively inexpensive that if we could use it better and address the supply situation, to your point, it seems unlikely that it would go away in 10 or 20 years.

Dr. Robert Svatek:

Right. I mean the big downside is people don’t want a catheter placed. You know, Rick, you’d rather take a pill.

Rick Bangs:

Anytime.

Dr. Robert Svatek:

Anytime. So, I think that’s one of the major challenges to BCG. Although I do want to say that the effectiveness is well worth it, I think. And, I do try to reassure my patients that, yes, having a catheter in briefly for a moment to instill it is undesirable. But what we do get from it is, I think, worth the risk, the benefit ratio is definitely to their benefit.

Rick Bangs:

And there’s nothing pleasant about an intravenous chemotherapy treatment either in terms of getting it delivered, let alone the side effects. So, it’s like everything in else in medicine it’s got its benefits and it’s got its risks or side effects. So, it’s the nature of the beast. So, Dr. Svatek, I want to thank you so much for your time today. I think you’ve given us a much better understanding of this unique treatment called BCG, let us know about the BCG shortage, and how to potentially navigate it. And some future alternatives for BCG.

Dr. Robert Svatek:

Rick, thank you so much for taking the time to have me. I appreciate it.

Rick Bangs:

Okay. And in case people would like to get in touch with you, could you share your email or Twitter handle or any other information that you’d like people to have?

Dr. Robert Svatek:

You can look at our website at UT Health San Antonio. My Twitter handle is @svatekrob. R-O-B. Shoot me a message.

Rick Bangs:

Okay, great. Just a reminder. If you’d like more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today. Thank you for listening and we’ll be back with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Svatek.

Dr. Robert Svatek:

Thanks, Rick.

Dr. Robert Svatek:

Hi, my name is Rob Svatek and I have disclosures that may be relevant to this talk. I’m a consultant for eUROGEN, Fair Gene and FKD Therapies. I participate in clinical trials that have drug provision, including [Erapav 00:46:05] by [Entura 00:46:06], TICE BCG by Merck for clinical trial S1602 and Tokyo BCG by Japanese BCG Laboratories for S1602. 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.