Thanks so much. Really appreciate the time and the opportunity to present here, and thanks for everyone for coming. There's a lot going on right now at BridgeBio. We have 3 phase IIIs already commenced or about to commence in ADH1, achondroplasia, and LGMD2I, and obviously an important phase II data set reading out later this year in congenital adrenal hyperplasia. I wanted to spend the entirety of my time today talking about a key program in ATTR cardiomyopathy, one of our big catalysts that's upcoming this year, which is the final readout from our phase III ATTRibute-CM trial. I wanna spend some time on, just move this forward to slide 2, the key questions highlighted on this second slide.
First of all, what are the clinical expectations from this trial? How might we compare the clinical data that we produce from ATTRibute-CM to already available therapies? Specifically, what does superiority look like? I want to then tie those clinical expectations to commercial expectations, where we've done quite a bit of work, as you'll see, in trying to understand what relative market share we can expect based on the wide variety of outcomes we might get from this clinical trial.
Let me start on the clinical expectations segment. Before we get into the expectations and projections, I want to take you back about 10 years to where we as a field started in the context of the ATTR-ACT trial.
Recall about a decade ago, what you can see against the most important Y-axis in the entirety of this field, which is that of survival, you can see that the placebo arm of ATTR-ACT delivered over the course of 30 months 57% survival, which is consistent with the dramatic unmet need associated with ATTR cardiomyopathy. On the top of this chart, you can see an 85% survival rate, which is what we believe the best you can do in this space, e.g., this is what life looks like outside of ATTR cardiomyopathy. We arrive at this number by effectively calculating for a mean 77-year-old what survival would look like over 30 months with the attending comorbidities that we observe in our trial associated with AFib, hypertension, and type 2 diabetes. Eighty-five percent looks like life without ATTR cardiomyopathy.
57% looked like survival some decade ago. Hearteningly, you can see with the partial stabilizer tafamidis, they were able to move a little less than halfway up, but deliver a compelling 70% survival rate over the course of their 30-month trial. Over the course of the next decade, something very interesting happened, which is absent pharmacologic intervention, absent therapy, medical management improved. We got better at diagnosing these patients, moving from a cardiac biopsy to a technetium scan-associated type of diagnosis. We were better able to treat these patients with more aggressive diuresis and putting them on fewer and fewer counterindicated medicines. Over time, what we saw, as you can see here, was an elevation of survival rates, again, absent pharmacologic intervention.
The largest five observational studies that have been conducted since 2018, if you take the average of them, as shown here, suggest that 74% survival is achievable, again, without pharmacology in this space. That means, to put another way, that the placebo arms of our trial and every other trial that are run after this are likely to outperform the on-drug arm of the ATTR-ACT trial, very interestingly. What's possible now in the context of better medical management and more potent stabilization? We show that on this final slide. We have last patient, last visit in our ATTRibute-CM study, and we know now that the blinded, blended survival rate is around 80% in our trial.
Our hope is that our drug is able to separate meaningfully from placebo and drive survival rates on drug above 80%, closer and closer to the world or the life without ATTR cardiomyopathy. If we're able to do that, we believe that would be a profound advance for the clinical community and the patients that we serve. Furthermore, we'd like to do that while also attending to cardiovascular hospitalizations, a key parameter that both physicians and patients say is important. Here on slide 7, I'm showing you the mean frequency of CV hospitalization events per year as reported from the ATTR-ACT trial, 0.884 on placebo. Unfortunately, in excess of hospitalization on therapy as driven by tafamidis, 0.999. You can see the mean frequency of CV hospitalizations per year going the wrong way.
Our hope is that we're able to have a definitive and beneficial impact on CV hospitalizations, both important in terms of quality of life and quality of health for our patients, also important from a pharmacoeconomic standpoint. Recall that each one of these hospitalizations is about $16,000-$20,000 per year. That's what's possible, there is a flip side, obviously, to the fact that the event rates are meaningfully lower and that survival is meaningfully higher in the context of these current trials and in the context of ATTRibute-CM. The last time we were at 80% survival rates, there was no meaningful separation between therapy and placebo. These are the curves that are associated with the ATTR-ACT trial, you can see a little over 18 months in where they reached a blinded, blended rate of approximately 80%, there was no separation.
We need to believe that we have a more potent drug to separate those curves at a time or underneath the conditions that prior therapies weren't able to. We believe we have that more potent drug, as we show on this next slide. I think many of you are familiar with this data. Our drug sees more target being less albumin-bound, binds the target more effectively having a superior Kd, and glues the target together more effectively upon binding with its superior enthalpic binding mode. We've demonstrated this across four assays preclinically.
We've demonstrated this with a better serum TTR level in the clinic in our phase II and the part A readout of our phase III. We've demonstrated this against NT-proBNP, a key biomarker in this space. We believe we have that more potent drug that can overcome this higher bar that's attended in our trial based on the fewer number of events. What does all that mean in terms of what we can expect from the trial? On the left-hand side of the slide I'm showing you here on slide 10, you have our base case outcome, starting with number one, obviously achieving statistical significance on our primary outcome, which is a hierarchical analysis with a win ratio as the primary endpoint. The second, the provision of unprecedented survival, 80%+, which we haven't seen in this space before, with clinically meaningful separation from placebo.
Finally, best-in-class performance on key serum biomarkers, suggesting again that we have a more potent stabilizer, and those key serum biomarkers were the ones I just discussed on the prior slide. On the right-hand side, you can see what we believe is the best possible outcome from this trial, which inclusive of the three things I just mentioned, adds on to it best-in-class CV hospitalization performance, as well as best-in-class win ratio performance, which is the primary endpoint of this trial, bettering the 1.7 that was put up by Pfizer in the ATTR-ACT trial. What does that mean in terms of market share? In the left-hand side, you can see about a 25% market share based on our extensive analysis that I'll go into in a moment. On the right-hand side, you can see about a 40% market share.
The range is relatively tight, no matter what analytic methodology you use. It's a little underneath, to be frank, what I had hoped when we first went into doing some of the research, but I think the 40% is consistent with second entrant movers in large categories like this, as you'll see in a moment. Keep that 25%-40% in your mind for a moment, and I'll move into exactly how we calculated these numbers over the course of our commercial work in the last 6 months. I'm gonna start, though, by reminding you that this market is large and that this market is durable, which will set the context for how one understands the absolute numbers associated with each one of these market shares. I don't think there's much controversy in this room.
Most of you know that the market is already $3 billion large, growing at above a 50% CAGR, and there are three significant tailwinds that are driving the increase in this market. Absent underdiagnosis, recall we probably only diagnosed one-sixth of the patients with ATTR cardiomyopathy in the U.S. alone. The first tailwind is the Inflation Reduction Act, which although might be at broadly hard for this industry, for this category is good because it will take co-pays of some $14+ thousand on Medicare Part D for these small molecule stabilizers and bring them down to a little over $2 thousand, making today what is an unaffordable set of medicines affordable. We believe that doubles the market in the U.S. alone. Secondly, ex-U.S. geographic penetration.
Recall, Tafamidis is just coming online or hasn't even come online in key geographies such as the United Kingdom, Spain, Italy, and others. As we grow internationally, we expect to see the market grow. Finally, improving and increased diagnostic awareness will continue to drive this market. One of the things that you see on category after category, especially in the cardiovascular markets, is that as more brands come on, as more sponsors come online, you see a growth of the TAM in a way that you wouldn't see with a, with a single sponsor. Ultimately, we think this is a $10 billion-$20 billion market. Market consensus right now from analysts is about $10 billion.
You can see here a calculation that we've done suggesting about a $20 billion total available market inclusive of the impact of the IRA. The market is large. The market is also durable, we believe. I don't think there's much controversy around the fact that our IP goes out to 2039. There have been some questions that we've been fielding around what does the tafamidis IP estate look like. With PTE, it's very clear if you do a little bit of work, that they are protected out until at least 2029 in the U.S. and 2030 in the EU. Our strong belief is that the crystalline form of VYNDAMAX is gonna be protected out to 2035 in the United States.
We've had two separate law firms look at this as well as our chemists, and we believe it for the following reason, as shown on slide 16. Recall that there are two ways, obviously, to challenge and genericize a brand. Number one is the challenge of the IP for obviousness. That is actually occurring in the context of tafamidis in Europe today. Looks like Pfizer has a strong case and will prevail in Europe. Europe being a tougher market to prevail in in terms of obviousness challenges than the U.S., so we think that they will be able to overcome that issue. The second issue, however, though, has to do with formulation in CMC. Pfizer did something very interesting in that they patented the lowest free energy form of the 61 mg form of VYNDAMAX when they were going to market with that drug. What does that mean?
That means that anyone who actually manufactures generic VYNDAMAX will either have that low energy, lowest energy free form in their formulation, therefore violating their patents, or they will have to run a bioequivalence study akin to ATTRibute-CM , which generic manufacturers tend not want to do. You'll literally either have to violate the laws of thermodynamics or you'll have to run another phase 3 trial to overcome this patent estate that goes out to 2035. We think the market's actually fairly durable out to 2035 in the U.S. Now, what happens between 2035 and 2039? We've looked at a wide variety of cardiovascular categories, and what you can see is that when one brand genericizes, it's not as if the entire category genericizes.
We intend to run a wide variety of phase 4 trials to continue to assert our elevated potency and superiority within this space. You can see in the antihypertensive space, the Factor Xa space, the diabetes spaces, et cetera, here's a statin example, that when one brand goes away, it's not as if every other brand goes away. When Lipitor went away, for instance, in 2012, as shown here on slide 17, Crestor sales continued to come along because there were certain sets of physicians that were reaching for a more potent LDL reducer. We believe the market is durable, not only out to 2035, when we believe tafamidis will go away in the U.S., but also from 2035 to 2039, when we'll continue to be able to sell underneath our IP.
All right, within that large and durable market, how do we start to estimate the market share? It wasn't just by calling three or four or five physicians, but rather by employing what is a relatively standard set of techniques to really understand what the ultimate market share in this space could look like. We started, obviously, with expert interviews, but we buttressed that with the ever-important preference share survey, here covering some 185 or so physicians, which is extraordinarily important because that's really 80% of the prescribing universe today.
We also talked to ex-commercial executives, talked to market access and payer panels, looked at industry databases, importantly, both to look at sales trajectories of analogs, but also to look at volume trajectories of analogs because sometimes pricing can allow you to misinterpret what relative share might look like, and then public databases associated with clinical trial data and labels. We employed these all together in kind of a mechanism where we looked bottom up using the physician survey and using the physician interviews, and we looked top-down, looking at categories, mostly cardiovascular and other categories akin to cardiovascular categories, to understand what second entrants might look like, both from a sales perspective and a volume perspective. As I'll show you over the course of the next few minutes, what was compelling is the remarkably consistent set of results that we got.
Market range is at a base case within 25% and 40% on the high case. I'll start with the preference share survey, which I think is one of the most important tools in this space. I'll train you on to the left-hand side of this chart, which is what we might expect in a two-player market. In a two-player market, you can see in the best possible scenario, us getting 58% of share, 52% in the base case scenario. When we move over to the four-player market with two stabilizers and two knockdowns, those numbers come down to between 27% in the base case and 40% in the best possible case. As many of you who have used preference share surveys know, you have to take a haircut on these numbers.
They tend to overestimate the market share of any entrant brand, taking a 10% to 20% haircut on these numbers gets you into the range that we're talking about, and I think it's consistent with the numbers that I stated prior too. These numbers roughly agree with what we saw from our HCP-detailed 15 KOL analyses, which is effectively that in the best possible case, you're looking at 39% in the 2-player market, in the base case about 25%, and again, in a 4-player market, those numbers come down to 34% and 20%. Again, well within the ranges that we're talking about from 25% to 40%. What was quite interesting was when we looked top-down at a number of different case analogs, we saw roughly those same ranges once again. Here's how we looked at sales share benchmarking.
We started with all products in the known universe from the EphMRA ATC level 3 database. We removed the small categories, removed the categories where there was a multiplicity of indications because sometimes that overlap in sales between different indications can confound your results. We were left with sort of 98 brands and 36 different categories that had either two players or four players. We looked at those and tried to understand how second entrants might perform. You can see here on the left-hand side in two-player markets, us skewing pretty close to that 60/40 type thing that many of you who are in sales and marketing may have learned when you first entered the industry is 64% for the for tafamidis and 36% using RTPP Or, I'm sorry, just for the second entrants in these categories, not using RTPP.
In 4-player markets, the mean of about 37% for a second entrant. I think what was really interesting is we did this work over the course of about 7 months and prior to an important paper getting published last week in Nature Reviews Drug Discovery from BCG, where they actually looked at relative market shares for first, second, third, and fourth entrants in large markets. You can see here data from one of their figures. They were looking at the present value of global sales, so a little bit different than absolute share at any given point, but relatively close. You can see here, I'll just point you to the second column for second entrants that are either clinically differentiated or effectively me too, but with not a significant liability, that share looks somewhere between 46% and 38%.
Interestingly, as you move from the middle row to the top row, you don't see a gain. Actually, you see a slight loss, suggesting that there are a great many other levers that need to be pulled just outside of clinical differentiation to really drive share as a second entrant, I'll get to that in a moment. I'll be brief on the volume share benchmarking because it largely agreed with the sales share benchmarking. What you can see from our data is that second entrants tend to price more aggressively. I don't think that'll be the case in this category.
As we looked across some 40 brands in terms of ATC level 3 groups, we actually supplemented that with some of the brands we saw in the BCG paper as well, arriving at a total of some 70 brands and 26 categories that we were able to look at volume, or share scripts across the categories. We found again that the second entrants gets about 32% in the case of a 2-player market and 29% in the case of a 4-player market, again, well within the ranges that I articulated at the outset. How do some of these second and third mover brands actually overcome the first entrant? You obviously. History is replete with these types of examples from the Factor Xa's to actually the statins, as we were mentioning earlier, to SGLT2s.
You can see some of the examples here that are either near CV or within CV. I think PAH is an interesting category to look at. A wide variety of commercial levers that can be pulled. Many of them have to do with access and pricing. Some of them have to do with HCP segmentation and how one serves clinical communities in different ways. Oft times, they are supplemented or buttressed by real-world evidence or key phase 4 clinical trials that are run, which certainly we intend to do. Sometimes they have to do with sales and marketing, innovative DTC, or using other types of promotional models. You can see there are a number of tactics that we're obviously thinking carefully about. We hope to employ them.
We hope that we get an upside case, and we're hopefully able to drive above 40% market share. 25%-40% market share within a durable market that looks like it's between $10 billion and $20 billion is our base case set of assumptions against this trial if it is to hit in late July. Another upside driver that I alluded to at the outset of the talk here is that TAM can actually grow significantly as multiple brands enter, and I think it's pretty obvious what that's driven by, increased awareness, increased diagnosis, and increased patient access. You can see some concrete examples here coming from both CV as well as from the cancer space with CDK4/6.
I'm gonna wrap up there and just remind everyone of the key points that are being made here today, and we're happy to get into these in our one-on-one discussions or in the hallways. We're also gonna post these slides plus many of the analytics that go underneath some of the numbers that you've seen today on our website just immediately after this talk. First and foremost, we believe there's a profound opportunity to improve survival in this space above 80% and getting toward the effective space where ATTR cardiomyopathy risk is fully eliminated. Secondly, we think there's a profound opportunity as well to reduce hospitalization rates. All of that comes within the context of having a higher bar. There are fewer events today against which a therapy like ours can effectively separate from placebo.
Separation itself will require a more potent drug than we've seen in the past. If we're able to separate and get onto the playing field, we believe that this market is large, and we believe that it is durable. We believe that a set of market share estimates that you can use a wide variety of analytic techniques to arrive at suggests we would be somewhere between 25% and 40% of this market, absent using some of the upside levers that I talked about. Other drug categories suggest that we should and could use tactics such as market access, real-world evidence, phase 4 clinical studies and the like to hopefully exceed those 25%-40% range and drive up above 50%.
I'll stop there with a few minutes for questions if anyone has them, or we can pick it up in our one-on-ones, and thank you for your time.