Welcome, everybody, to the next session of this year's 2025 Global Healthcare Conference. I'm Mani Foroohar, Senior Analyst in the Genetic Medicines team,
I'm good. Thanks for having me. Appreciate it. Yeah, originally, Tom and Chinmay were going to come up here, and we got here, and they said, "All right, have fun." They are here if you guys want to chat with them. It is great to see everybody, and thanks so much for having me.
A pleasure. We don't get to spend a lot of time with you. You're obviously busy with the Attruby launch, commercial preparation, et cetera. We're going to spend most of the conversation on that, and that's a lot of the debate.
Sure.
On the stock, at least near term. I know you started with on the Infigratinib side, though I would assume you're spending most of your time with Attruby launch now.
Yes, yes. I've been with BridgeBio almost seven years now, started on the QED side with Infigratinib, but I've been spending a lot of time on Attruby leading up to the approval in November, and then obviously now through the launch.
Let's talk a little bit about the launch dynamics. I think we've seen a couple of updates around scripts. I don't think it's surprising to us that there is a large pool of undiagnosed patients. Exactly how large that pool is remains an open topic of debate.
Sure.
Let's talk about the nitty-gritty of the launch. A lot of the debate is the flow from diagnosed patient, script, through the various mechanisms down to what's the real net sales. I know you can't give us a number, and I'm not asking you to give us guidance.
No, of course.
Walk us through what you can and can't influence in terms of places where you can improve your yield.
Sure. I mean, I think a lot of it depends on, first, who is filling the script, where is the script getting filled. Is it getting filled at a specialty pharmacy? Is it getting filled through a specialty distributor at a hospital? Did the patient use a free trial? From there, typically a prescription then goes through the insurance companies, and how quickly do they want to approve? With our free trial program, patients can get on Attruby within 24-48 hours, and the physician's office can work on the prescription after that for the first paid drug. Some things can happen during that. People often say, "Well, what might happen in between the prescription being written and the first commercial script getting paid?" Typically, everything runs pretty smoothly, but sometimes people pass away.
These are older, sick patients, so you can see something like that. It is not conversion rate isn't 100% for any medication. Typically, we've thought a lot about this. We've really put a lot of details in. We call it white glove service just to make sure that anyone who wants to get Attruby can actually get it.
When we talk about white glove service, people think immediately about, "Oh, Patient Hub, et cetera." Something we've seen across the rare disease space.
Yeah.
This is a little bit of a larger indication than most rare diseases.
That's true.
Medium rare, maybe. Let's talk about when those physicians are seeing these patients. Are we getting the initial free script for 28 alongside the paid script, or is that something that comes later? Mechanically, how does that work out? How is that going to flow through to eventually what we see on your revenue reported?
Yeah. I guess I'll start. Everyone says they have a white glove service, right? Every pharma company has a hub. Every pharma company says they do white glove service. When you actually dig into the programs, you realize that that's not the case. If you just sort of stack up everyone's programs side by side and you look at the rules and the qualifications, you can sort of quickly see who is truly offering more and who is just sort of making the medication available. I think we try to separate ourselves out by making it as easy as possible. You hear that a lot from our organization. Make it easy. How can we make it easier? That's for healthcare providers. That's for patients.
I think that's sort of the first differentiator is people, meaning healthcare providers, once they try our programs, they're more likely to want to try and use that program again. Not everybody uses a free trial. A lot of the big centers, for instance, sometimes at first, they'll say, "I'm worried. What if I put someone on a free trial and then I can't get their prescription through the insurance company?" We've actually gotten that question. Why do you think that insurance companies will cover this product? The first thing I sort of point out is the price of the drug. Attruby's $244,500 and change a year. That's 10% less expensive than tafamidis. We'll see if patisiran gets approved and what they do with price, but they're in the high $400,000s right now, so almost double the cost of Attruby.
Typically, if someone writes a free trial, they get the drug in 24 to 48 hours. They oftentimes write the first commercial script to go along with that, and the free trial gets filled, and then within the 28 days, the first script gets filled as well. It gives the doctors a chance to get experience with the drug if they haven't used it before. It gives the patient a chance to see how they're doing, how do they feel, are they having any side effects? It's really kind of a, I don't know, it takes a little bit of the pressure off of everyone because it's also free. It's pressure off the payers as well. Like, is this drug going to actually do, and how will people do on it? I think it's a nice chance for people to see we've promised a lot.
Are we actually going to show up with it? You guys have seen some of the numbers we've put out so far. It looks like the answer is yes.
Let's talk a little bit about the mechanisms on a payer perspective. I know this is a topic that has become a major debate on Wall Street.
All right.
It may or may not be as relevant in the real world, but let's talk about the dynamic of having a small molecule oral drug.
Sure.
Or D. Two of them, in fact, tafamidis and now acoramidis. In a market where you presumably will have a competitor that's a Part B in-office injectable.
Sure.
To some extent, perhaps at-home infusion with a nurse, et cetera, as Alnylam was established more so during the pandemic and polyneuropathy.
Sure.
Let's talk about that Part B versus Part D dynamic in terms of patient out of pocket and then payer obligation.
Sure.
As you know your price, I'm presuming the price for which we spend stays around where it is now, which is what we project.
Sure.
Walk us through what that means for different patient populations in Medicare and commercial insurance from an out-of-pocket patient perspective and a payer perspective.
Sure. I mean, some of this is just truth as of today, and some of it we'll speculate. If assuming they keep the price where it is, what would that potentially look like? Some of it depends on what does the physician want? I should probably start all of this. I think most patients will get the medication that they want with a few assumptions. That would assume that the price didn't stay where it is for patisiran. I think if the price stays where it is, they have to probably do some contracting. Why do I say that? The way B versus D works is we'll just take MAPD plans, which is the majority of lives. If you're in an MAPD plan, the payer, so patients pay up to $9,350 for a Part B as in boy drug.
For a Part D as in David drug, the max is $2,000. Patients already have a much higher potential out of pocket. From a payer perspective, what happens? On the Part D as in David side, let's take Attruby. You take the $244,500, you minus off $2,000, you're at $242,500. What happens is the payer is responsible for 60%. That's one of the new changes. Everyone's sort of freaked out, and they were like, "Oh my gosh, 60%? That's much higher than they've had to pay Part D." Everybody's going to be in big trouble. When you actually look at that, it's 60% of $242,500. I sort of joke. Everybody in this room probably just did that math in their head. I can't do that math without a calculator. Let's take the other side. Part B as in boy.
Let's just say, for argument's sake, that the price is $480 for Patisiran when they launch. You take $480, just we're doing easy math here. We take the $9,350 off, call it $10,000. Now we're at $470. The plans are responsible for 100% of that. I can do that math in my head. So 100% of the $460 or 60% of $242,000. There's a huge difference. It makes Patisiran for the plans about three times as expensive as it does for Attruby. If you think about it, then on the MAPD side of things, the patient out of pocket is potentially higher. Payers out of pocket is definitely higher. What will happen? Honestly, I don't know. I mean, I know this is like a you guys are talking about this all the time.
My personal view is if a physician says, "I want a particular medication," and it's approved and the plan is allowing it for anyone, then they're going to allow it. So the plan will make a decision to allow a medication to be written or not, and then it probably gets approved. What happens behind the scenes with contract negotiations and rebate requests and all of that? I don't think anything on the D side is really happening with that. I think on the B side, there is such a discrepancy now. Probably something has to happen. I'll just add one more thought on that. IRA used to be two years ago, Part D was a little bit worse than Part B for patients because the out-of-pocket on expensive drugs was really high. The out-of-pocket for Tafamidis two years ago was about $16,500 every year.
Every January, patients had to come up with that money. IRA fixed that. Now all oral drugs are $2,000. You can smooth it out over 12 months. Patients pay a max of $167 a month for all of their oral drugs combined. As soon as they have hit the $2,000, everything is zero. Attruby could be $0 if someone is already on another Part D medication. For ATTR-CM patients, on average, these patients are on seven or eight other medications. Part D, this actually was a really good thing. Part D now is pretty good for patients. The problem is they flipped it a little bit. Why should a Part B patient pay $9,350 if the Part D patient is only paying $2,000? I do not think they should. The reality is right now, that is how it is.
That probably also has to be fixed. You really should just have we believe in parity access for all the drugs. Unfortunately, there are still some imbalances. Hopefully, that gets fixed. In the meantime, companies have to try to react to that. That was a long answer to your question, but I hope that covered it.
Let's follow up on that parity access question. You guys have given a little bit of numerical clarity on how you think about parity coverage with Tafamidis, which is approved in the market. Talk to me about what your experience has been in terms of contracting access, et cetera, and how many prior auth medical exemption hoops are we jumping through at this point in the market?
Sure. Yeah, it's not that bad. I mean, most of the majority of the lives for Attruby and Tafamidis are off formulary. The reason for that is you guys probably heard of adverse selection. Plans don't want to put really expensive medications on formulary because you take a 70-year-old person, they're looking to renew their healthcare. What do they do? They go look for all of their medications and they see which plans cover them. When they find their Tafamidis listed or their Attruby listed, they'd say, "Oh, cool. I want this plan." Plans know that. They're not trying to attract patients on expensive medications. They want to attract the 70-year-old who's in great health.
They offer free flu shots and free physical exams, and that person's not sick, and they say, "Well, that's a pretty good deal." They just remove all of the expensive meds from the on-formulary listing. It doesn't mean you can't get that medication. You just do it through a medical exception process. Medical exception process is actually pretty easy. In many cases, it's easier than a prior auth. Prior auths can get a little long. Medical exceptions, for the most part, are pretty standard short forms. Our sort of positioning to the payers is, "Listen, we're the least expensive, so just start right there. If somebody wants to use Attruby, you pay less, either just because the WAC is lower." That's pretty simple.
The more complicated discussion with the MAPD patients, when they think about what they're truly paying, Attruby is significantly less than the other medications on the market. You look at hospitalization rates. There is no head-to-head trial, so you can't do a head-to-head comparison, but they just sort of look at Attruby and they say, "Okay, what happened to the patients?" Attruby reduces hospitalization rates by 50%. So far, that's the best number anybody's been able to show. When you're thinking to yourself, "What should I cover? What should I do?" we come out and we say, "Cover everything." We just want equal access, whether we're all on formulary or all off of formulary, and then we'll go fight it out in the physician's office and we'll see who can convince the physicians of what.
From a payer perspective only, if they write Attruby, you'll pay less, and the hospitalization rates look really good. Payers are paying not just for medications. They have to pay for all the ancillary costs, including hospitalizations. Hospitalization costs for an ATTR-CM patient are significantly higher than what a typical sort of admittance looks like for a standard patient. They add all of that up, and Attruby looks pretty good, and normally we have very good conversations. I don't know, I would say the reimbursement's been very good so far.
Let's take the conversation to the physician's office. Obviously, a lot of the uptake here has been newly diagnosed patients. The more companies you have in the space, the more awareness there is.
Sure.
To what extent is the competition to expand diagnosis one that is in media? To what extent is it one that's at professional associations, guidelines-driven? What needs to happen to move these diagnosis rates up, not 1 or 2%, but step function increase?
That's a great question. I mean, I think it is moving fairly rapidly. You think about where we were five years ago and sort of where we are today. The average patient takes years to get diagnosed, which is a problem because this disease, as it you imagine your functionality is up here, right? You're walking to the mailbox to get your mail. You're hanging out, playing golf, tennis, whatever you like to do. You start getting the shortness of breath. You're not sure what's going on. You misdiagnosed. These patients, on average, can go four or five years before they're actually diagnosed. I think that is changing a bit because now people are starting to say to themselves, "Could this be ATTR cardiomyopathy? I should check." If I want to check, you no longer have to do a heart biopsy.
You can just do a PYP scan. Those are readily available, highly reimbursed, and inexpensive. You could check their serum TTR levels, also a very inexpensive test, which would give you a hint. I think for it to change rapidly, we're going to have to see more physicians looking sooner. Not waiting until, "I can't figure out what's happening because I've been trying all these other things that aren't working." I think that's happening to a greater extent. I mean, if you just run some ICD-10 codes and you look at just look at the number of HFpEF patients that are out there. You know for sure from a conservative perspective, 12-15% of those patients have ATTR cardiomyopathy. You run the math on that. Clearly, we're nowhere near where the sort of true denominator should be.
I think when you start thinking like that and you get physicians thinking like that, they start looking. When you start looking, you find it. It's not that hard to find. It's interesting. You speak to physicians and doctors, and they sort of say, "You know what? I should have found that." They had bilateral carpal tunnel. They had back surgery four years ago. You start kind of running through all of the symptoms, and you're like, "This is an obvious ATTR-CM patient, but it wasn't obvious at the time." I think when that happens, you're going to see this big jump in patient perspective. Maybe AI will help. Maybe there's a way to dig through patient records and figure out who's likely. You just run one of these inexpensive tests to rule it out.
Let's talk a little bit about subdividing the patient population and sort of segmenting who goes where. There's a universe of patients that are on Tafamidis already. Some of them might be early adopters. Some of them may be more severe. However, they ended up already on Tafamidis versus those who remain undiagnosed. Is the undiagnosed pool, is it more Medicaid? Is it older? Is it more urban? Is it more rural? What differences? How should we expect this market to evolve as it becomes more and more driven by this large undiagnosed pool of patients?
That's a great question. I mean, I think there's definitely some unknowns. What we do know, I mean, right now, roughly 24,000 patients are on Tafamidis. You could say that 30-40% of those are probably progressing. So there's sort of like, what do you do with that group? That's a pretty large number of patients. Then every quarter, there's 2,000-3,000 new patients, newly diagnosed patients sort of coming in and stacking up on top. At what point does this not become a rare disease anymore? What is sort of the tipping point, so to speak, on that? I'm not sure what that looks like because I really still think we've just barely started to scratch the surface. I think what will happen is you're going to see a shift. Right now, to your question, most of these patients are Medicare.
I would say 80-85% of this market today is Medicare. I think you're going to start to see a shift towards younger because the question is, and we're actually looking at this as a company, what happens if you treat them sooner, start treating sooner? Can you prevent this loss of functionality that I was talking about earlier? This becomes a chronic disease. They don't run into these sort of debilitating quality of life issues that happen. They're not in the hospital, and they're not dying from this disease. They're dying from something else, which, of course, is the goal of chronic disease. You can't prevent death forever, but you can prevent death from that particular disease. I think if we can shift people to getting treated earlier, sooner, you then prevent all these complications that come along later. I think that's when things get pretty exciting.
If you could get diagnosed at our average age in our clinical trial was 77. They did not get the disease at 77. They obviously had it, and we are sort of building up to being diagnosed for many, many years. I think we can do a better job to get people educated to look sooner, find it sooner, and get treated sooner.
Let's talk a little bit about what happens as you have a new entrant entering, presuming that Vutrisiran's is approved and Amvuttra's approved for their supplemental filing, and they remain somewhere in the realm of the current price range. Let's talk about the competitive dynamic for newly diagnosed patients versus those patients who are progressing on Tafamidis. How do you think about the physician selection? Is there different patient populations that you think are going to be driven towards one or the other? Is it a function of location and setting of treatment? How do you think about the competitive positioning?
Yeah, I would say two things. One, location of treatment. It's not an accident that Alnylam is really trying to increase how many people could potentially get their medication at home. These are older patients. They don't want to drive. Some of them can't drive. Now they have to be driven by a family member. If they're going to be treated at a center of excellence, that can involve a multi-hour day very easily. I don't know the last time you guys have gone to a clinic like a center of excellence, but by the time you drive there, find parking, go through security to get checked in, find which elevator. These people are often short of breath, so you can't just walk through the hospital. You may need a wheelchair to help you get there. That's an event.
There will be patients who say, "You know what? If I could take pills at home, remember with the other seven medications I'm already taking. So we're just going to add a little bit to throw the pills, drink a glass of water. You're done for the day." Most of them are on blood pressure medications, all these other things. They're taking pills multiple times a day. So we're really not impacting sort of their daily routine. If I have to get in my car or have my son or daughter drive me or whatever that might look like, they're taking off work, that can be an issue. I think for sure site of care will motivate patients one way or another. From a physician perspective as well, some of them are set up to do shots. Some of them are not.
Some of them want to take on the risk of a $500,000 drug and can cash flow that. Some of them can't. I think all of those will sort of play in. I think it's like, "Okay, well, so now what? I'm on Tafamidis, and I'm progressing. What am I looking for as a physician? I want something that's going to work really quickly." I mean, these patients are progressing. This is a serious disease. It does kill you if you can't get it under control. Attruby showed separation from placebo as early as three months. That's the fastest that anyone's been able to show results. Again, it's not a head-to-head trial, so I'm not sort of saying like, "Oh, look at this, not at that." That's the data that the physicians are looking at. It's super impressive.
This is in today's population, which typically are healthier. You would not expect that separation to show at three months. You would think it would take much longer. It did take much longer for the other drugs. It does not mean they are not effective. It does not mean they do not work. Doctors like to see something that is going to work quickly, as do patients, because you are in this mindset of, "I am progressing." Remember, that loss of functionality, you do not get that back. Once I am on this sliding scale, I used to golf. Now I cannot. I used to walk to get my mail. Now I cannot. It is not like you magically go back in time and get all of that back. You have to stop the progression so that you can maintain where you are.
I think all of those things will weigh on the physicians' and patients' minds and in terms of then what they want to select.
I think one of the conversations that I've had with many investors is, well, everyone is eventually going to progress on whatever medication they're on. And so shouldn't we just be assuming an almost equally massive second-line market to first-line market? Let's talk about the duration of therapy. Once a patient starts to progress, whatever that means, on their first-line agent, what does that mean in terms of how long that patient's going to be on whatever their second-line agent is? How should we think about survivability, etc., and just the life cycle of the patient in first-line versus second-line therapy?
Sure. I guess I would challenge that a little bit too because will they all progress? I mean, we just said, say, 30% or 40% of Tafamidis patients are progressing. That means 60% or 70% aren't. For those patients, Tafamidis is working. I think our argument is that's with a partial stabilizer. Attruby is the only drug that has near complete stabilization in the label. We set out to be a stabilizer of over 90%. We proved that, and now we have that in the label itself. I think the question is, if I take a partial stabilizer or I take a partial knockdown, which is what Patisiran is, right? They only knock down 84%. You still have the other 16% of the tetramers falling apart. Remember, it's the monomers that are toxic. The tetramers are great. Everybody has them.
Everybody in this room has them. They're performing a function. Part of what keeps you healthy is once they start falling apart that the issue arises, and then those monomers deposit, and that's what's causing the problem. If we stabilize over 90% of the tetramers, do you progress? Some, sure. But how many can we reduce that number and we get back to something else? Sounds a little like morbid and depressing, but I actually think it's encouraging. You want something else to get you, right? You don't want it to be your ATTR-CM. Sure. Okay, let's say, all right, fine, but what about those Tafamidis patients? The argument is, what should we do? Should we switch mechanisms of action? Should we go from a partial stabilizer to a partial knockdown? Why?
You should go from a partial stabilizer to a near complete stabilizer that costs less both for patients, doctors, sort of the whole system benefits. Let's do that first. I think for many patients, you'll never do anything again. That's going to be your last medication. The trickier question is, okay, but then what if the doctor thinks that they're ultimately progressing again? What do you do then? Do you switch MOAs, or do you add and do combination therapy? That's an expensive proposition. I'm not sure that we have the data yet to determine what that is. You're basically saying I've stabilized greater than 90%, and I'm going to then knock down 84% of the remaining 10%. We're starting to split hairs a little bit, but we'll leave that to the physicians to decide if they think that makes sense.
If they think it makes sense, then to the payers to decide if they want to pay for that.
We're down just a couple of minutes. I just want to touch base very quickly on where we are in Europe and Japan, respectively partnered with Bayer and Alexion International Genetic Company. I know you are primarily responsible for the US. Talk to us a little bit about how we should think about the flow-through from European demand, the opportunity set there. Obviously, pricing is different. We don't have some of these Medicare complexities because those are often single-payer monopsony markets.
Yeah. I mean, and then the rest of the world too. I mean, we can talk about what BridgeBio is doing even beyond that because there are a lot of larger markets. Think about Brazil is one that just comes to mind. Huge opportunity, lots of patients in Brazil who have ATTR-CM. I think Europe is difficult from a pricing perspective, right? We all know that every medication, the price tends to be, there is pricing pressure, more pricing pressure than what you see in the US. The difference is, though, once you jump through all of those hoops, anyone with a diagnosis gets the medication. In the US, that can be a little harder sometimes, right? You go through the prior auth process or the medical exception process. There could be a denial.
Figuring out insurance, every plan is different, and so it can be much more complicated. In Europe, once you get through the pricing conversation, the difficulty is sort of off the table. If you need that medication, it's covered and paid for. I think the opportunity is quite large. Bayer is an amazing partner. I think we're very happy to have them on board with us, and I think they're going to do a very good job launching in Europe, probably with Germany as the first launch.
I think we're over time. Matt, thank you. I'm sure we're going to continue this conversation as the launch progresses.
Appreciate it. Thanks very much.