You think about viral genetic medicines. What do you think about? What are the problems with that? You can't get much. You can't get a large number of genes in there, right? You're limited on packet size. You can't re-dose, right? And they're really expensive to make and complicated, and you've got all the specialized handling. With a non-viral approach, we have none of that. By bringing a product through the bladder mucosa, we're able to solve many of these issues. It is very much unique, very much a unique opportunity in that way. Now, when you think about bladder cancer itself, the focus of where we are is in non-muscle invasive bladder cancer, which is the majority of patients. That's about 730,000 patients in the US and about 85,000 new patients a year. This is an early form of bladder cancer.
It's a slow progressing form of bladder cancer. Be clear, it can be a very serious form. If you land up in muscle invasive or if you land up in metastatic disease, it's pretty tough. NMIBC patients kind of present in roughly three different ways, right? They have what's called carcinoma in situ. These are sort of hard, flat-type tumors, right? They're all over the bladder, right? They're tough to get at because you can't cut them out, really, right? You have other growths, papillary growths, a Ta, which you see here grows in the bladder but not deeply into the lamina propria, or a T1 where it's deeper. Those patients have even a worse prognosis. To the point that I made about this disease, that's a little bit about the prevalence and the incidence.
This is a disease that's an early form of bladder cancer. It progresses about 20% over 10 years. When you think about oncology products or cancer products, you think about metastatic diseases, you think about you got to do something very quickly, and you got to have the most potent agent because that patient may only live three months. This is a totally different situation. First of all, it's managed by urologists, and it's a slower progressing disease. It is a common disease. It's the sixth most common, and it's expensive for the system to manage, right? $6.5 billion estimated per year. This is how the traditional treatment has occurred. Quite frankly, it's you diagnose the patients, you give them BCG if you can get it, right? If you can get it.
It's not the easiest therapy, and it becomes more toxic the more BCG you give to individuals. Right now, you either go with IV chemo, right, where the efficacy is so-so. You try some of the new therapies, clinical trial. Ultimately, patients that land up with the real option is removal of their bladder, right? Radical cystectomy, boy, oh boy. This is, you're talking about your fathers, your grandfathers in general, right? Average age 75 for this disease, right? You're exposing them to a pretty high mortality rate, and their morbidity is pretty tough, right? You land up having a stoma, having a stoma bag, right? In the surgery, men lose their prostates. They often lose sexual function. It really is a really tough surgery and has a high level of morbidity and mortality.
That's why the FDA in 2018 came out with some draft guidance to say, "Look, if you do a single-arm study, 100 patients, you're good to go," right? With that, you see three products were approved. Despite those three products being approved, the FDA reissued guidance in the summer of 2024, and said, "We still need new products." That tells you about the unmet medical need. Now, the unmet medical need for the target audience is also different. What do I mean by that? First of all, urologists are mostly in the community. That's where the patients generally are. Two-thirds of urologists practice in some sort of community setting, right? When they think about what they need, and if you look on the right, right, a little bit of market research done here, what do they value?
They value tolerable agents. Remember, these are average age 75-year-old men, right, with a lot of comorbidities. You do not want to add something else with a lot of side effects. Tolerability is important. Obviously, efficacy is important. If you add up some of the things that fit in the logistics of the practice there, you see that they are pretty important as well. Their treatment considerations are different from that in the academics. Some of the things that they are dealing with are chronic staff shortages, not many urologists, not hard-to-get nurses, right? Many of these practices are increasingly being owned by private equity. There is revenue pressure, right? They used to make funds from surgeries or in-office procedures, but those are becoming less attractive. More and more of these practices are looking at buy-and-bill as a source of revenue, right?
You see that it used to be only 5% of the revenue, but growing into the 15%-20%, right? Products that they can administer that does not alter their practice flow, right, and that they can get buy-and-bill revenue from of 6% become much more attractive to them. That is where detalimogene voraplasmid comes in quite nicely, right? I'll share with you some of our preliminary efficacy numbers, but we're showing an emerging competitive efficacy profile. I'll show you some of our tolerability data there again, looking like a very well-tolerated product. Because it's a non-viral gene therapy, storage, handling, shipping, administration is easier.
When you look at that, when I said at the very beginning, this product was designed for the needs of busy urologists, you can see how it solves some of the problems that I teed up for you a little bit earlier. What is detalimogene voraplasmid? What is the product, right? Effectively, what detalimogene voraplasmid is, is we literally take a simple plasmid. We put in that plasmid two RIG-I agonists, right, and IL-12. I think many folks are familiar with IL-12 as being an effective product, but probably toxic, right? Very difficult to administer. What does that do? That activates both the innate immune system and the adaptive immune system. The product is administered intravesically. You think about the bladder being bathed with this product, right? That is how you get at these carcinoma in situ lesions or cyst lesions, right?
When you look at on this chart, the little purple dental images, what are they really made up of? It's made up of four simple ingredients that are readily available on the marketplace: regular, standard, off-the-shelf plasmid DNA, where we put the genetic cargo, what I talked about previously. We combine it. This is the secret sauce, the proprietary sugar polymer. That's what gets us through the bladder wall. We mix those very carefully to get a nanoparticle. We throw a little PEG on top of that to stabilize, and there we go, right? Four simple ingredients, no special sort of handling. We're already manufacturing at scale. I'm actually super pleased that we're well on our way through our validation batches, which are often called PPQ batches.
I think many of you are aware that in this category, manufacturing products and being able to fulfill market demand has been a real issue. We feel really good about that. Because it is four simple ingredients as well, from a cost of goods perspective, this is a really competitive cost of goods as well. We are really pleased with the progress we have made on the manufacturing part. Where are we on the clinical part, right? This is our program here. It is the LEGEND program. We have multiple cohorts for the LEGEND program. The most important is the pivotal cohort, which is in BCG-unresponsive NMIBC patients with CIS. They are the toughest patients. We are delighted to report that we actually finished enrollment in this study, and we hit 125 patients. We are pretty pleased about that.
We have three other cohorts to provide some other information to physicians. One cohort for patients that have not had BCG, another cohort that have had various amounts of BCG, and a third cohort of patients who do not have CIS but just have papillary disease. There is some precedence for that last cohort with NCCN guidelines. Individuals have received some reimbursement for that. Of course, we do have a, we discovered this platform, the DDX platform, this elegant platform. We are looking at ways to take detalimogene to other diseases, but we also have other products that we are making. Wrap it all around the fact that we have a very strong IP estate. That is something that people often forget. Because this platform was discovered by us, we have a lot of prior art.
We're at least into 2040 and likely beyond that as well. Let me drill down a little bit on the LEGEND program and on the pivotal cohort. What is it, right? I've talked about the patient population. It's a global study, open label. It's 125 patients. How do you get detalimogene? What's nice about it is intravesically, week one and two, nice little break, week five and six, rinse-repeat three times more that year. In the following years, the maintenance is half the dose. Much less than even BCG or some of the conventional agents. We've recently had a dialogue with the FDA around our endpoint. We're aligning ourselves with the other approved products. The primary endpoint is the anytime complete response rate. Now, how do these 125 patients that we've enrolled broken out, right?
We have 94 patients where we announced last year, after we shared some data, that we were going to make some protocol amendments. We thought we lost some efficacy on the table. We were not treating these patients with standard of care. That is the majority of the patients, 94 patients. Last September, we shared 21 patients. There were 10 patients in process. There were 31 patients here. You see the vast majority of the patients are being treated under this amended protocol. We are actually starting to engage with the FDA in a statistical analysis plan discussion. That 31 patients will likely be smaller than that. The majority of the patients are patients that have been optimized. How do the post and pre-protocol patients look from a baseline characteristics perspective?
You can see here it is predominantly male, older gentlemen who've had a lot of BCG. They are pretty similar. The one thing I would note here, though, our patient population relative to some of the other products that have had pivotal programs has more high-risk characteristics. I always caution individuals about making comparisons between trials, right? Particularly these trials of 100 patients or less. This sort of speaks a little bit to the difference in the patients, the differences in the protocols, and the difference in the way these studies are announced. As I said before, we shared some pretty good data last year about our efficacy and our tolerability. We actually felt we left some efficacy on the table. I am happy to share with you what our post-amendment patients look like, right?
Now, of that 94 patients that I said before, we have data of only 62. Of those 62 patients, had they had a complete response at any time, 63%. That's exciting. That's pretty much in the range of where all the other products that have been approved. We're in range there. Three months of 56%. The number that folks have been focused in on was the 62% six-month rate. How does that compare to what we've shared previously? That's a material increase versus our September data. How does this compare to other products? Right in line with recently approved products and recent data. We're pretty excited about that.
Now, one of the big protocol changes that we made was to say after three months, if you are a non-CR, right, and if you have a Ta lesion, the one I shared here, a little growth in the middle of the bladder, before we said, "Well, you can't have drug again." Now we said we can resect those patients. So we are re-inducing patients at three months that are non-responders. We're delighted that four patients actually had "a delayed response" and have become responders. That's great news. The next question that you have is that, "This looks terrific, Ron, and you're in line with others. What about longer-term data?" The reality of it is most of these post-protocol patients are patients from this year. We just haven't had many patients who've been on drugs very long.
The first five patients that have made it to nine months, all five are complete responders. It is small, right? It is small, but it does sort of indicate that we are in the right direction. Now, these numbers are obviously going to change. If you look at the 94 patients, there are 57 patients that are still in motion, either have not had a three-month assessment or a six-month assessment. These numbers will change. This is a snapshot in time. I have to say, with the protocol amendments, I think we are pretty pleased with the improved CR rates. I think this is an evolving competitive profile. Your obvious question is, "How does that compare to what you showed before, right?
What happened from before? What you see here in the patients before, so the top of this chart is what I've just shared with you. The patients that were treated in the previous protocol, you see that the six-month rate was 41%. To my point earlier, I think we made a material difference. Now, there are patients in the pre-protocol group that were on drug for a longer time frame. What we've said is for those patients that the long-term CR rate is below those products that have already been approved in this area. Part of that is, though, getting back to the other comment I made earlier, we're in a dialogue with the FDA on those 31 patients. We don't know which of those patients are going to be in the analysis or not.
In fact, because we have the RMAT designation, the Regenerative Medicine designation, we've already had a lot of dialogue with them. We absolutely know that there is a large cohort of patients that are going to be removed. The majority of the patients will be based on the post-protocol amendment patients. We're pretty excited about that, given that we've had that 63%, right? If we say, "Okay, evolving competitive efficacy profile, if you have more efficacy, do you have more side effects, right?" No, in fact, the tolerability has really held quite nicely. You see here 42% treatment-related adverse event rate. Most of the AEs are associated with the catheterization, to be honest. They're relatively mild. We're introducing a couple of new points that I think are pretty important here. I'll come back to this later on.
How does this tolerability manifest itself on patients staying on drug or taking drug on time? You see here a 1.6% dose interruptions and a 0.8% dose continuation. Effectively, what we're saying is that patients can tolerate this product and they'll take it on time. They want to continue to take it, which is absolutely excellent as well. If you take the evolving efficacy profile, you look at the tolerability, and then you say, "What does it look like from a patient and a practice perspective?" The practical applications of a non-viral gene therapy are pretty exciting, right? From a patient perspective, they don't have to go in for as many installations, right? Who wants to be catheterized many times? If you can be catheterized less, great. While you're there, it's only an hour in the clinical trial.
It's about five minutes to put it in. In real life, when we talk to the FDA, likely these patients will not have to stay in the clinic because we're collecting urine and the like now. There's no bleaching or any requirements because it's not a virus, right? At the same time, for the practice, you don't need any special equipment, right? You just store it in the fridge or the freezer. It can be administered by anyone in the staff. The nurses can do it. You don't need a special room. You can just do it in an examining room. There's no decontamination of the room or any extra special precautions that are needed. I've talked about detalimogene in isolation here.
From an efficacy perspective, from a practicality perspective, let me move to it in the context of some of the other approved products, right? In the middle, this is the post-amendment patients. I shared you the 63% CR rate anytime. If you go to the products that are in development or approved to the right, you see pretty much within that range as well. As I said, that number is going to change a lot with 57 patients moving. We're in the right zip code. If you look at the CR rate anytime, 62% for detalimogene in the Bond 3 study. For the CG product, it is 63. The recently approved J&J product is 59. You see we are very much, as I said, in the same area, evolving competitive efficacy profile.
From a tolerability perspective, that 42% as it compares across, very competitive. If I take you down to dose interruptions of 1.6%, all the other agents are in the 30s and 40s, right? That really speaks to a great tolerability profile. If you then think about the logistics and the convenience, right? What does detalimogene allow you to do, right? There is no complex shipping and storage, right? You can just keep it in your fridge or your freezer. There are no pre-washes. There is no bleaching afterwards. One administration, right? There is no need to decontaminate the room or have a special room just for this product, right? There is nothing that the patients have to do after. They do not have to avoid loved ones. They do not have to bleach their urine, any of that stuff.
You do not need to find a nurse that will handle a virus, nor do you need an infusion chair and all that. Big checks for dental imaging for things when it comes to simplicity. When you look at the other agents, there are some things that you will need to do. That is a competitive profile from a simplicity standpoint. I think what we are kind of excited about is for patients with this disease, which is high risk, right, that are facing right now likely having their bladder removed, these options are actually providing them many, many more years with their bladder. Historically, what used to happen, you get a diagnosis, you can get BCG, then they cobble together a bunch of chemotherapy trials and other stuff, and then they take your bladder out. We see a future now that is pretty exciting, right?
Where, again, you'd start with BCG, right? We see, because of what I talked about, that emerging efficacy profile, tolerability, and convenience, it just makes sense to use a non-viral approach. Reach into the fridge, off you go. Then use one of the chemos that are available, right? There'll be multiple chemos available. Likely, as it becomes more complicated for the patient and for the practice, off you go to an academic center for perhaps a viral therapy and a checkpoint inhibitor, right? That is a pretty exciting change from what patients had before. We're hoping that many of these individuals will keep their bladders for a long time. Hopefully, they pass from something else other than their bladder cancer, right? Just closing off, look, we've put together a top-notch team that's launched lots of products, developed a lot of products.
You can be rest assured that the dental imaging is being curated carefully with this team. Just to close, pretty excited to be here today, particularly on the back of sharing a data update. We just really believe that this market is going to change. It's going to be a market of where you'll be sequencing multiple agents. All of these agents are going to be used. We just believe that our product, just because it's just easier to slide into the workflow of community urologists, where most of these patients are, just makes a lot of sense. Just also to believe that as you think about your fathers, your grandfathers who have multiple diseases, have multiple doctor visits, multiple drugs, I think they want something that is well-tolerated and they don't have to go there very often, right?
You're catching us at a pretty exciting time as a company because we're going to plan on a data update with some of our longer-term data. After we talk to the FDA in the second half of next year, filing, and then a potential approval in 2027. Wrap it around with the fact that we have cash to get us into 2027. We're in real great shape. Again, thank you for the opportunity to be here today for an exciting time with the company. I'm happy if we have a minute or two to take a question. Thank you, Ron. That was great. I know the data is relatively new at this point, but was just kind of curious if you've had an opportunity to use any of the community docs as a sounding board for the data that you generated.
I was also just wondering what the community has been saying just about the expected uptake of J&J's TAR-200, which I know is getting a lot of airtime as a new entrant to the market. I think there's a lot of enthusiasm with the community docs. We had the pleasure of having, if you have an opportunity to listen to the webcast of our data release, we had the pleasure of having a community doc with us, right? Just one of a group. Just that emerging competitive efficacy profile, tolerability, if you go back to that market research, that's really important to them. How it slides into their practice. This is emerging quite nicely. Now, frankly, the wider group of community urologists are just so busy seeing patients and doing procedures, right?
They don't know as much about these emerging products, but once it gets approved, I think it's going to be exciting. I'm super excited about the approval of the J&J product. I think it's going to be a very important product. Uptake will be strong. It's going to take a little while to work its way. Every launch is never a straight line. I know the community is looking forward to that because from in their practice flow and in the equipment they need, they're already using gemcitabine intravesically. This is just a more convenient way to do it. It'll slide in very nicely. Again, it goes back to our belief that this disease will go from more of an incident-based disease, much more to a prevalent-based disease. A product like J&J will help that.
But the reality of it, all these products at 12 months have a complete response rate of somewhere between 20-40%, which means recurrence occurs 60-80% of the time. It is really important to keep bridging these patients and bring on new agents. All of these new products are really important for patients. Do we know offhand kind of what proportion of those patients experiencing recurrent disease are then no longer eligible for treatment because they have been kind of reclassified out of non-muscle invasive from a risk stratification perspective? Yeah, this is an important question. There is a subtle difference here, right? When you talk to doctors, recurrence is okay. It is no big deal, right? They can just add new medicines. Progression is a problem. The reality is this is a very slow disease. There are not many patients that progress quickly, right?
There is lots of opportunity for these agents to make an impact on patients so that these individuals can keep their bladders, right? Which is really good for them. Maybe a naive question, but what is the rationale behind the agency's prioritization of CR at any time as a primary? Again, I never want to speak to the agency, right? In my experience, that is really a measure of does the product work or not, right? CR at any, so if you are making a take it from a treater's perspective, what do you think about? You think about, does this product work? Is my patient going to take it and tolerate it? Can I get it? Can it be reimbursed, right? A good proxy for is it going to work is CR at any time means it will work at some time.
There's a lot of subs below that. I think that's where the agency, and I never want to speak for the agency, but I would hypothesize it's really about does this product work or not? That's probably the best management for that. Yeah, I think a lot of our KOL feedback would suggest that they prioritize CR at any time, but also with some suggestion of durability as well. I think you showed it on your community market research slide, right? The importance of 12-month CR was 2x higher than that of CR at any. Yeah. The reality of it is if it works at any time, but it only works for a month, that's not great, right? If you get something that can work for a longer time frame, that's terrific.
In a disease where there's multiple options and these are older gentlemen, if you had few options, durability would really be a really serious choice driver. In this case, these are older gentlemen, ages 75, with five or six, seven different options depending on things work out. We should be able to bridge them if they don't progress. It'd be different if you were a 50-year-old individual, you had a cancer, and there was one treatment. You want as much durability as possible. Obviously, durability is important, right? I would argue as long as it's not so tiny, it doesn't make a difference, right? With multiple treatment options, we can solve that issue there. I guess if recurrence is the base case, then having a convenience and tolerability advantage probably would put you somewhere at the top of that funnel.
You are sitting in the seat of a busy community urologist with tons of patients, right? With pressure on their practice economics, right? What are you going to use? You are going to use a product that works, that is well-tolerated, and that fits into the flow, right? We see detalimogene as sort of a first-line, first choice. Then you get to things that are more complicated over time. More logical. Okay. Ron, we really appreciate it. Congrats again. Thanks very much. Appreciate it. Bye-bye.