Madrigal Pharmaceuticals - Q2 2024
August 7, 2024
Transcript
Operator (participant)
Good day, and thank you for standing by. Welcome to the Madrigal Pharmaceuticals second quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.
Tina Ventura (Head of Investor Relations)
Thank you, Luella. Good morning, everyone, and thank you for joining us to discuss Madrigal's second quarter 2024 earnings. We issued a press release this morning and have a slide deck that accompanies this webcast, which we'll post on the investor relations section of our website right after the call. On the call with me today is Bill Sibold, Chief Executive Officer, and Mardi Dier, Chief Financial Officer. They'll provide prepared remarks, and then we'll take your questions. Our goal is to keep today's call to about 45 minutes. Please note on slide 2, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of risks that may cause actual results to differ from the forward-looking statements. With that, I will now turn the call over to Bill on slide 3.
Bill Sibold (CEO)
Well, thanks, Tina. Good morning, and thanks for joining. I'll cover three topics on our call this morning. First, an update on the Rezdiffra launch, where we are off to a strong start this quarter. Our key metrics are also showing strength and are consistent with market research, reflecting high physician awareness and intent to prescribe. Second, our progress wiring the system, where we are four months into what we expect to be about a 12-month process. This is our number one priority. As with other first-in-disease launches, we are driving a change in clinical practice and physician behavior and developing processes for efficient patient and prescription flow. Our goal is to establish a strong foundation to support peak sales. And third, our strategy to maximize the long-term value of Rezdiffra.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
In addition to the untapped opportunity in the US, we announced today that we plan to directly launch Rezdiffra in Europe, following an EMA decision expected next year. Let's start with the launch on slide 4. As discussed in our first quarter call, we are providing second quarter metrics on 3 key areas: demand, including patient numbers, payer coverage, and prescriber uptake. We generated $14.6 million in net sales in the second quarter and exited the quarter with more than 2,000 patients on Rezdiffra. In addition to driving demand, we have put a lot of focus on the time it takes to fill a prescription. With the physician community, Madrigal patient support, specialty pharmacies, and payers, our field team is focused on patient selection with prescribers.
Our patient support team and the specialty pharmacies in our limited distribution network are driving efficient prescription processing, and payers are executing on medical exceptions more efficiently because they recognize the unmet need. As a result, patients are moving more quickly through the reimbursement process. We have previously discussed our expectation for time to fill, to improve from about 60 days at launch to about 30 days or less at 6 months. Because of our efforts, time to fill was running faster in the second quarter compared to those initial expectations. We're also very encouraged by the progress we've made with payers. They understand the significant unmet need in NASH, which is the number one driver of liver transplants for women in the United States.
They also recognize the clinical benefits of Rezdiffra for F2, F3 patients, and that non-invasive tests, or NITs, not biopsies, are standard of care. Last quarter coverage was at 30% of commercial lives. As of June 30, more than 50% of commercial lives now have coverage in place for Rezdiffra, with over 95% of Rezdiffra-covered lives accepting NITs and not requiring biopsies. We are well on our way to achieving our goal of 80% of commercial lives covered by year-end. As far as government payers, as of July 1, Medicaid coverage was in place across all 50 states. Similar to what we've seen with commercial coverage, virtually all accept NITs and do not require biopsies. For Medicare, we are on track for full coverage beginning January 1 of next year, based on the annual review process for new medications.
Currently, Medicare patients are accessing Rezdiffra via the medical exception process with prior authorization requirements consistent with our label. We are pleased with the progress we have made with the 6,000 top hepatologists and gastroenterologists that we are targeting, who are caring for the vast majority of the 315,000 diagnosed F2, F3 patients. In the second quarter, approximately 20% of our top targets wrote a Rezdiffra prescription, which is aligned with the penetration level often seen in launches of blockbuster medicines. As you'd expect, early in launch, we've seen hepatologists adopting more quickly due to their expertise with the disease and NITs. Gastroenterology practices can take a bit longer, given that NASH isn't their primary disease area, and they need to think through practice dynamics for patients.
Across the board, each physician is at a different stage of activation, and we continue to steadily add prescribers. Our top targets are writing more than 75% of prescriptions, giving us conviction that we're targeting the right physicians with our efforts. Significant opportunity remains to expand new prescribers and shift initial prescribers to more frequent prescribers. To do this well, we need to continue to successfully wire the system, as noted on slide 5.... We're in the early stages of what we expect to be about a 12-month process to substantially accomplish that goal. Just like other disease states with first-time treatments, we are working to change physician behavior and help build a pathway to efficiently process Rezdiffra prescriptions at physicians' offices. We've made great progress. We are steadily adding patients and prescribers, but it's early in the launch, and there's still a lot of work to do.
For physicians, it's about educating on the risks of NASH and activating them to write a prescription. The risks are real, and they are urgent. For example, our health economic study of an Optum claims database highlights alarming rates of progression to adverse liver-related outcomes. Of 19,000 NASH patients without cirrhosis at baseline, approximately 17% progressed to decompensated cirrhosis within three years. In addition to disease state and Rezdiffra education, we are also helping physicians identify the appropriate patients for Rezdiffra using NITs, as well as using the recently published U.S. expert panel recommendations and EASL guidelines. For the office staff, it's about helping practices create a pathway to process patients and prescriptions to handle the future volume we anticipate. This can require additional staff to manage patients and navigate the evolving reimbursement process.
For payers, we continue to have productive dialogue on the costs of NASH, the clinical benefits of Rezdiffra, and non-invasive testing of patients. That's been paying off with favorable Rezdiffra coverage. For patients, we're continuing to educate them on NASH and Rezdiffra while helping them navigate through the complexities of the healthcare system to support their treatment journey. We're absolutely doing the work physician by physician, practice by practice, payer by payer, and patient by patient. This is a tailored approach that requires discipline, repetition, and time. As accounts become wired, the pull-through process becomes smoother, and it's easier to send more prescriptions through. We're still in the early stages, but we are confident that we're building the foundation needed to create a blockbuster medicine. The optimism of our U.S. launch drives our decision to directly commercialize Rezdiffra in Europe, as noted on slide six.
We have been evaluating our Europe strategy following the submission of our marketing application earlier this year. We expect an EMA decision mid-year next year, which would make Rezdiffra the first NASH treatment available in Europe. Our decision to commercialize Rezdiffra in Europe allows us to preserve the full value of the asset, maintain strategic flexibility, and create a platform for future growth. Europe is an attractive opportunity for several reasons. The NASH patient population in Europe is significant. NASH is driving a marked increase in the prevalence of hepatocellular carcinoma in Europe. From 2016 to 2030, cases of NASH-related HCC are expected to increase by more than 100%. We've established Rezdiffra as a potentially foundational therapy in NASH through our MAESTRO-NASH phase 3 clinical trial. We have 125 trial sites in Europe.
We've formed strong relationships with the NASH European community through our clinical development program and on-the-ground presence with our European Medical Affairs team. Rezdiffra has been favorably positioned as first-line therapy for moderate to advanced NASH, consistent with F2, F3 fibrosis in the EASL Clinical Practice Guidelines. This was despite it not being approved yet in Europe. The guidelines also note that Rezdiffra is the only disease-specific agent in NASH with positive results from a registrational phase 3 clinical trial. We are starting to build the infrastructure now to commercialize Rezdiffra in Europe in 2025. Another key aspect of our lifecycle management strategy is expanding the use of Rezdiffra to patients with compensated cirrhosis, as seen on Slide 7. There is an even higher urgency to treat patients with cirrhosis because they are at a 42 times higher risk for liver-related mortality.
Our MAESTRO-NASH Outcomes trial evaluates Rezdiffra in this patient population. It's an event-driven trial that non-invasively measures progression to liver decompensation events in patients with compensated NASH cirrhosis. An indication in this patient population has the potential to double our opportunity. Let me conclude by summarizing our progress on Slide 8. We have the enviable position of being first to market in NASH, giving us a strong and sustainable competitive advantage. We are fully leveraging this opportunity, positioning ourselves for long-term leadership in the U.S. and now globally with our expected launch in Europe. We have a highly desirable product profile. It's an effective, once-daily, well-tolerated pill. It's a liver-directed medicine that has demonstrated the ability to halt or improve liver stiffness in 91% of patients out to three years.
We've resourced the launch to match the opportunity in front of us, starting with an expert team that's launched dozens of blockbuster medicines. While we're still early in the launch, we're making good progress on many metrics. Net sales of $14.6 million, more than 2,000 patients on drug, more than 50% of commercial lives covered, virtually all except NITs and do not require biopsies in line with what we have communicated. Approximately 20% of our top targets have prescribed, with significant room for growth. Recently published EASL guidelines and U.S. expert panel recommendations endorse Rezdiffra as a first-line therapy for F2, F3 NASH. We have more work to do to change clinical practice, to educate and activate physicians, and to help them create efficient care pathways for patients.
We are steadily adding patients and prescribers and tracking right in line with what we would expect at this point in the launch. As we look forward, we are well on our way to building a blockbuster medicine with patient expansion as we execute on the untapped opportunity in F2, F3 NASH, indication expansion, as we look forward to data from our outcomes trial in cirrhosis patients, and geographic expansion as we plan to launch Rezdiffra in Europe next year. Before I turn the call over to Mardi, let me briefly reflect on the progress we've made as a company. I've been in my role 11 months, and what we've accomplished is pretty incredible. I'm very proud of this team. The FDA accepted the Rezdiffra filing. We received priority review. No AdCom was required.
We very quickly built an expert team at the leadership level and the commercial level, including a full field team ready to support the launch on day one. We built sufficient supply. We received approval with a best case label, importantly, with no biopsy requirement. The team was out promoting Rezdiffra within weeks of approval, and we shipped product in less than a month. We have been building strong physician relationships. We've seen favorable Rezdiffra guidelines published. Payer coverage is favorable and virtually all plans not requiring a biopsy. So we are executing on everything that we said we would. We're making progress. It's early, and there's still more work to do. As we look forward, we are about a third of the way through our plans to wire the system to build a strong foundation to support our aspiration for peak sales.
We have the right strategy in place to do that, and we're even more confident in the significant potential of Rezdiffra. So with that, Mardi?
Mardi Dier (CFO)
Yes, thank you, Bill. The press release we issued earlier today contains our full financial results, so I will provide a few highlights, as noted on slide 9 for the second quarter of 2024. U.S. net product sales for the quarter were $14.6 million, comprised of demand and inventory. For the quarter, it was mostly demand. We expect inventory to run between 2-4 weeks for Rezdiffra, as is typical for a specialty medicine. Gross to net was favorable to our expectations for the quarter, as our co-pay assistance was lower than anticipated for this particular quarter. As we said, we expect gross to net to be choppy quarter-to-quarter, particularly this early in the launch. R&D expenses for the second quarter 2024 were $71.1 million, compared to $68.6 million in the second quarter of 2023.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
We continue to anticipate a relatively steady level of R&D expenses for the rest of the year. SG&A were $105.4 million, compared to $17.8 million for the second quarter of 2023. This year-over-year increase is as expected, as we discussed last quarter, due to the scale-up of our commercial operations following the March approval of Rezdiffra. With the announcement of our intent to launch Rezdiffra in Europe, we expect a modest increase to related to our infrastructure build in 2024 and more so in 2025. Moving to our balance sheet.
The balance of our cash, cash equivalents, restricted cash, and marketable securities as of June thirtieth, twenty twenty-four, stood at $1.1 billion, which is slightly higher than what we reported last quarter, due to the closing of the greenshoe from our March public offering and proceeds from option exercises. With our strong cash position, we are well-resourced to support a successful multi-year launch of Rezdiffra. I'll now turn the call back over to Tina.
Tina Ventura (Head of Investor Relations)
Great. Thanks, Mardi. We will now open the call for questions. We would like to limit questions to one, as we're trying to get through as many questions as possible today. Luella, if you could open the call.
Operator (participant)
We will now open the lines for question and answers. To open your line, please press star one, and you will be added to the queue on the call. Our first question comes from Thomas Smith with Leerink Partners. Please go ahead.
Thomas Smith (Senior Managing Director and Senior Research Analyst)
Hey, guys. Good morning. Thanks for taking the questions, and congrats on the nice launch quarter. I was just wondering if you could... I appreciate all the color in the prepared remarks. Just wondering if you could just elaborate and maybe quantify a little bit more within that $14.6 million of net revenues. How much of that was due to underlying patient demand and prescriptions being filled, versus how much of that was related to initial inventory and stocking? Thanks.
Bill Sibold (CEO)
Great, Tom. Thanks. Mardi?
Mardi Dier (CFO)
Yeah, great, Tom. Great question. How we're gonna characterize this, characterize the demand versus inventory in the $14.6 million in net sales, is that it's mostly demand for this quarter. So we're really pleased how our team performed cross-functionally and, you know, had a nice result for the quarter. However, we just want to reiterate that the typical days on hand for inventory moving forward is two to four weeks, as we've seen with most specialty medicines. We also want to reiterate that we're at the beginning stages of our launch, right? We're about a third of the way through what we think we need to wire the system. So we just want everyone to be careful not to get ahead of ourselves as we look forward in the next quarter.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
I'll just make one other point that Bill made very clearly, that looking forward, you know, we had nice progress into our launch quarter and that we'll steadily add both patients and prescribers as we move forward.
Tina Ventura (Head of Investor Relations)
Great. Thanks, Tom. Luella, next question, please.
Operator (participant)
Our next question comes from Andrea Tan with Goldman Sachs. Please go ahead.
Andrea Tan (Vice President and Senior Equity Research Analyst)
Good morning. Thanks for taking our questions. Maybe just given the focus on the launch cadence here, just wondering if you're able to provide an update on patient numbers exiting July. I know you have the over 2,000 as of the end of the quarter. And then what proportion are on paid drug? Thank you.
Bill Sibold (CEO)
Yeah, thanks for the question, Andrea. Look, we're not gonna talk about month-to-month progression. I think the way we've characterized it is that we're steadily adding patients and prescribers, and that was certainly what we continued to see through July. As it relates to free drug, you know, there was very little this quarter. As we look towards the future, though, we expect that there'll be some more free drug as we have more patients utilizing the various services that we provide.
Tina Ventura (Head of Investor Relations)
Great. Thanks. Thanks, Andrea. Luella, next question, please.
Operator (participant)
Our next question comes from Akash Tiwari with Jefferies. Please go ahead.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
Hey, this is Amy on for Akash. Thanks so much for taking our question. So there is an inflection implied by consensus on Rezdiffra revenues next year. Do you feel like there will be a significant acceleration on launch trajectory next year once access is properly in line, or is your base case that launch will be more gradual? And then if I could just sneak in one more. Of the less than 5% plans that require a biopsy, can you give us a sense of the plans, what they are, and the covered lives? Are these mostly Medicare? Thanks so much.
Bill Sibold (CEO)
Sorry. With the last one, what we are talking about was commercial-covered lives, not Medicare, but, I guess Medicare we will have come online in January. So just to be clear, the greater than 50% is, commercial covered lives, so that's what the... Those were the stats around it. Regarding the uptake, you know, look, I think what we've been really clear about from the beginning is that we have to wire the system, and that it takes, time when you're launching a first-in-disease product, in a community that's never had anything to use, including anything that they went to, really in an off-label capacity. And we've said that that is about a 12-month process. We're about a third of the way through that for now.
Now, as we have, we moved through Q4 of this year, remember, then you get into Q1 of next year, and there's always the reset in Q1. So we're. That's why we've talked about the 12 months through Q1 of 2025, and in... By the end of that time, we'll have our reimbursement, we feel, in place. We will have physician practices that have been trained and just much more comfortable with writing a prescription and pulling it through. So that's when we expect to see that more patients we will be able to move through practices, both from a identification and just ease of ushering them through the whole process.
Tina Ventura (Head of Investor Relations)
Great. And wonderful. Thanks, Amy. Next question, please.
Operator (participant)
Our next question comes from the line of Andy Chen with Wolfe Research. Please go ahead.
Andy Chen (Director and Senior Equity Research Analyst)
Thank you for taking the question, and congratulations on the quarter. So if you can remind me, based on your market research among the 350,000 patients, what % of them are GLP-1 experienced? I'm thinking about a very hypothetical scenario where payers require GLP-1 step. I know that's not the case right now, but please entertain me for a moment. What fraction of these patients would basically bypass that requirement right off the bat? Thank you.
Bill Sibold (CEO)
Are patients experienced, Andy, or did you say physicians have experience with GLP-1s?
Andy Chen (Director and Senior Equity Research Analyst)
Oh, a patient experience.
Bill Sibold (CEO)
Patient experience.
Andy Chen (Director and Senior Equity Research Analyst)
Like in the past, they have used it. Yeah.
Bill Sibold (CEO)
Yeah, look, we're hearing from practices that there's more patients that have been exposed at some point to GLP-1. As you know, even in our clinical trial, we had 14% of patients that were on GLP-1. Now, that was on the diabetes dose, though, I'll remind you. However, we're certainly hearing that more patients are being exposed to GLP-1. Question always is, is when were they exposed? Was it 1 month ago, 6 months ago, or 12 months ago? Are they still on? And as you know, with the discontinuation rates, it could be yes to any of those answers. So, what we're seeing from our own data is that there are some patients that are concomitantly on a GLP-1, but it's still pretty early, and it's tough to get some of that information right now.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
Regarding payers, we haven't seen anyone requiring a step through a GLP-1.
Andy Chen (Director and Senior Equity Research Analyst)
Good. Thanks, Bill.
Bill Sibold (CEO)
Thank you.
Tina Ventura (Head of Investor Relations)
Luella, next question, please.
Operator (participant)
Our next question comes from Eliana Merle with UBS. Please go ahead.
Eliana Merle (Senior Biotech Equity Research Analyst)
Hey, guys. Thanks for taking the question, and congrats on the progress. You mentioned that you were seeing faster uptake with hepatologists versus gastroenterologists. Can you just give us a little bit more color on the latest trends that you're seeing with the gastros now versus at the start of the launch, and if you're seeing an uptake in or uptick in prescribing from the gastroenterologist segment? Thanks.
Bill Sibold (CEO)
Yeah, Ellie, thanks for the question. So I mean, look, it makes sense that hepatologists are gonna get off to a little bit faster start, right? They have been treating the disease. That's something that they know very well. They're familiar, very familiar with the liver. And so we did see the hepatologist get started a little quicker. Now, the gastroenterologist, there's a lot more of them than hepatologists. And, you know, they're working through their practice dynamics as well. As you know, there's a you know, pretty high focus on scoping in gastroenterology, so it's how do they make room in their practice, or how will they process a patient using oftentimes a lot of APPs, and you know, there are different stages of how do they actually process a patient through.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
Great interest in doing so, but there's just a practical matter that you're running a practice, and you now have to start to make room for that. And, you know, that's what we're spending time doing, is working with them. Now, there's, you know, a lot of gastroenterologists that are writing. You know, we talked about 20% of our target list, and the majority of that target list is gastroenterologists because there's just not that many hepatologists in the country. So we expect that gastroenterologists are going to be a key prescriber in this because there's so many, and that's where the bulk of the patients sit. And just as we expected, hepatology a little bit ahead, but gastroenterology making progress. And as we said from the beginning, we're steadily adding new prescribers and steadily adding patients.
Mardi Dier (CFO)
Great. Thanks, Ellie, for the question. Luella, next question, please.
Operator (participant)
Our next question comes from Yasmeen Rahimi from Piper Sandler. Please go ahead.
Yasmeen Rahimi (Managing Director and Senior Research Analyst)
Yes, team, congrats, really, on a solid quarter and all the great work. I guess you, you commented now that you're thinking about for 2025 into expansion into Europe as well as, you know, into cirrhotic patients. Could you maybe think about, you know, is your plans in Europe to really do this on your own and build a commercial sales force, or are you still between now and end of year, potentially entertaining, you know, a partnership that could allow them to commercialize and you could focus on the, on the US? So I would love sort of for you to maybe think about how we should be thinking about that, just because it's its own, you know, its own caveats involved in Europe. So would love, you know, like, are you fully committed? Do you want to partner?
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
What are your thoughts? Are there?
Bill Sibold (CEO)
Yes, thanks very much for the question. Let me provide the clarification. We're fully committed to commercializing on our own in Europe. We first of all, I've commercialized multiple products in Europe. In fact, every product I've commercialized has been globally. We have a team that has done that as well. So we feel like we're extremely well positioned to do so. Now, what's the ingredients to doing that? What we did here is, with the whole leadership team, is we built the right team and put them in place so that they could execute to do what they know what to do. That's the same thing that we're gonna be doing in Europe. You know, we will be very focused, targeted in the way that we launch.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
You know, likely starting point is Germany. And you know, one of the things that we've learned, or several of the things that we've learned, if I look at Europe, and a lot of it's coming off of our experience being there at EASL as well. You know, there's real excitement in Europe for the drug, and I would say if I look back at a year ago, though I wasn't here exactly a year ago, but a year before approval in Europe versus the US. You know, in the US, because there had been so many failures before, there was this question: Will Rezdiffra get approved? And a lot of the physicians didn't take action until post-approval. And when they said that they weren't gonna take action, they really meant it.
You know, they were waiting till the product was approved. Europe, there is, I would say, greater certainty for them because they believe that the U.S. approval is a good prognosticator for approval in Europe. And at EASL, we certainly heard that people were taking steps. We saw that leadership in Europe got very well organized and had the EASL guidelines out well in advance of approval, and despite not even being approved, put Rezdiffra in the lead position there.
So, you know, we think that Europe, as well as the 125 trial sites that we've had there, is quite experienced with, knows Rezdiffra, is excited about it, but, you know, we are gonna be very disciplined in the way that we approach Europe, and we'll be able to give you a little bit more updates on it as we progress throughout the year to tell you exactly how we're going about that launch.
Tina Ventura (Head of Investor Relations)
Good. Thanks, Yas, good question. Next question, please, Luella.
Operator (participant)
Our next question comes from Liisa Bayko with Evercore ISI. Please go ahead.
Liisa Bayko (Managing Director and Research Analyst)
Hi, thanks for taking the question. I wonder if you could give us a view on patient start forms at the end of the quarter, and then also just a little more color on gross-to-net. I know you said it would be a little choppy, maybe a sense of what it was and where you ultimately want to get to. Thanks.
Bill Sibold (CEO)
Liisa, thank you very much for the question. Let me start just with the, with the patient start forms. We're not giving any update on patient start forms. We are just providing the patients that were on drug at the end of the quarter. That to say, though, that you know, there are... You know, clearly, we're seeing steady additions to patients and, as I said, prescribers throughout the quarter and, you know, since the quarter. Maybe from a gross-to-net perspective, Mardi, I'll have you?
Mardi Dier (CFO)
Yes, absolutely. Thanks, Liisa, for the question. So our second quarter or our first quarter of launch gross-to-net was favorable versus our expectations, but it's all within the realm of what would be typical for a specialty product. We want to be clear about that. Sort of the biggest swing factor for us right now is the co-pay assistance program that we've set up to make sure that we can get and help our patients get on drug as efficiently as possible. We saw less use of our co-pay assistance program this quarter, but going forward, we expect that to grow a little bit. So that was sort of the essence of gross-to-net could be choppy.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
And then, of course, as you get into first quarter, you have other issues, with gross-to-net and IRA, et cetera. But that was the main driver for this quarter.
Tina Ventura (Head of Investor Relations)
... Good, thanks. Luella, next question, please.
Operator (participant)
Our next question comes from Ritu Baral with TD Cowen. Please go ahead.
Ritu Baral (Managing Director and Senior Biotechnology Analyst)
Good morning, guys. Thanks for taking the question. I wanted to ask a little bit more about the prior auth that you're seeing for the plans that have established coverage. Our own survey work and KOL work indicates there's a lot of MRE imaging and maybe MRI-PDFF diagnostic imaging required. Can you talk about access and what you guys are doing to assist access to those imaging technologies for diagnosis? And is that, is that consistent with the prior authorization requirements, diagnostic requirements that you guys are seeing in your finalized plans? Thanks.
Bill Sibold (CEO)
Well, thank you very much for the question, Ritu. You know, we are not seeing access to any of the NITs as being problematic. In fact, you know, we're actually really happy with what we're seeing as requirements. Most of them include imaging, yes, but blood tests as well. For the imaging FibroScan, MRE, MRI-PDFF, and then we also have ELF and FIB-4 from a blood test perspective. So, you know, it does vary, but there hasn't been anything that's been concerning, I would say. And as we map out the access that physicians have to these various technologies, they have very good access. Now, is it perfect? Does everyone have access to everything?
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
No, but, you know, we're at the very beginning here, and as I said, as it relates to NITs, I think it's gonna be a three-year process for NITs to sort themselves out. There isn't complete alignment in the physician community about which combos to use. There's new technologies that people are thinking about as well. So I think it's gonna take a few years before there is just real... Well, there may never be alignment, but I think that there's gonna be better information to say, what is the—are the combinations and sequencing that are going to be best for various physicians. So we think we're in a really good place. As you recall, you know, the big concern out there was, are biopsies gonna be required? And that just has not been the case.
You know, we talked about less than 5%. And, you know, now, you know, going back to this wiring the system, the challenge for practices is where historically, they just had to stage somebody and watch and wait. Now, they have to actually stage somebody as they're deciding to treat with Rezdiffra, and it's one thing to do it for staging. It's another thing when you start thinking about the implementation of a pathway which leads to the prescription of Rezdiffra, and that is kind of the muscle memory we talk about, where practices are getting used to that. The more they do it, the easier it is, so that it becomes more of a behavior change rather than a curiosity or, you know, going and trying to find a high-priority patient.
That's what takes the time here to get us to that steady state.
Tina Ventura (Head of Investor Relations)
Good. Thanks, Ritu. Luella, next question, please.
Operator (participant)
Our next question comes from David Lebowitz with Citi. Please go ahead.
David Lebowitz (Senior Research Analyst)
Thank you very much for taking my question. You had indicated the time to fill was coming in faster than the original expectations of starting at 60 days and eventually dropping to 30 days. Are we to assume that it's in between 30-60 days at this point, and it has actually already reached 30 days or potentially is exceeding 30 days?
Bill Sibold (CEO)
David, thank you for the question, and maybe just a little bit of context first is, you know, as we were out starting the launch, one of the real directions to the field was to help practices with patient selection. And that was a very conscious effort. The reason being is, you know, we've been clear from the beginning saying that we want only F2, F3 patients, and that's been partnership with the payers, too, letting them know that we're not trying to expand on either side until we have data. And I think this is a testament to the teams doing a really great job in that the practices chose the right patients so that their experience in gaining access, even if it was a temporary policy in place, it actually moved quicker.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
I think it's also an acknowledgment that the payers see the unmet need, and they don't wanna deny a patient that really needs the drug either, to get this. They know what happens when a patient crosses the line to cirrhosis. It's just, it's just not good. So that's, that's how I think I think that explains why there has been that acceleration, if you will. It was kind of deliberate to make sure we have the right patient and also the practices wanting to make sure that they only had so many resources and time. They didn't wanna get stuck having to fight back and forth, so they chose the right patients as well.
Now, as we scale this back up and you start putting more volume through, probably the quality of the prescription comes in, that can begin to drift a little bit, so you may not be able to move quite as fast. All we've said, in the time, is that we're directionally closer to 30 than to 60.
Tina Ventura (Head of Investor Relations)
Good.
Bill Sibold (CEO)
60 days, that is.
David Lebowitz (Senior Research Analyst)
Thank you for taking my question.
Tina Ventura (Head of Investor Relations)
Thanks, David. Luella, next question, please.
Operator (participant)
Our next question comes from Ed Arce with H.C. Wainwright. Please go ahead.
Ed Arce (Managing Director and Senior Research Analyst)
Hi, good morning, and thanks for taking my questions, and, congrats on this quarter. Just wanted to ask about the COGS, $0.6 million. Initially, I would think for the first few quarters, you're just working off of prior inventory, when would you expect COGS to normalize? And if you can discuss the rate there. And also, on the payers that require a biopsy, commercially, could you identify which one of those are and what pressure you think might exist over time for that to change? Thank you.
Bill Sibold (CEO)
Ed, thank you very much. Gee, you know, I don't have the list in front of me of the payers, and we're not gonna give specific to the plans, especially when we're still in a pretty dynamic phase right now. We still have some more work to do. Look, I think that any of the payers that have required a biopsy are beginning to hear that from prescribers and a lot of cases from patients and advocacy. You know, in a day and age where there are good NITs that allow for the appropriate diagnosis and staging, it's just not necessary to subject somebody to a biopsy, which has its own set of complications.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
So we would expect over time that those discussions will take place, and, you know, we're hopeful that those plans will come around. But remember, we always said that there would be an outlier. There'd be outliers. And as just as we said, there are some outliers out there that are requiring biopsy. So, you know, we'll keep working at it. We want. We don't want any patient to be subject to it, and that is what will drive our engagement with all the payers to make sure that patients are well treated and have an option to have non-invasive tests. On the COGS question, I'll turn that over to Mardi.
Mardi Dier (CFO)
Yes. Thanks for the question, Ed. You are right, COGS is quite low because we are burning off what we have set up in inventory currently, and we don't think COGS will normalize for about 1.5-2 years from this point, really depending on the demand on the top line, of course. One thing I would note that is, you know, we have a small single-digit royalty to Roche, which also flows through COGS, so that is a component. But I'll remind you, we're a small molecule medicine, so COGS for Rezdiffra is gonna be quite low.
Tina Ventura (Head of Investor Relations)
Great. Thanks so much, Ed. Next question, Luella?
Operator (participant)
Our next question comes from Jay Olsen with Oppenheimer. Please go ahead.
Jay Olsen (Managing Director and Senior Analyst)
Oh, hey, congrats on the launch progress, and thank you for taking the question. Of your 2,000 patients, can you comment on approximate proportions of F2 versus F3? And are you seeing any off-label use in F4s? And then since Bill has the benefit of leveraging his Dupixent launch experience, can you comment on the strategy and timing of communicating directly with patients? And how important is the direct-to-patient strategy with MASH, where patients may not be symptomatic compared to other more symptomatic diseases? Thank you.
Bill Sibold (CEO)
Jay, thanks for the question. On the split of F2 and F3, it's pretty even. You know, this... I think if you were to ask physicians, who would they rather start with, they'd prioritize the patient and say, "We'd probably wanna put an F3 on first." But the reality is, you can't control who's coming into your office that day, so they make a decision based upon what's- how's that patient feel, what is their- what do the NIT show, et cetera. So we see a balance, actually between the two. Regarding off-label, don't have any real insight into that.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
You know, we've been very clear with physicians who is appropriate and who is not appropriate for Rezdiffra, and make sure that they understand that we just don't have the data to support. And obviously, it's not in our label, so we would never ask for it or talk about a patient with cirrhosis. So we have no way of really knowing. Certainly, I haven't heard it as being a broadly. I think people are really focused on the right patients, and I think that's why, again, we saw a little bit better time to fill and so forth.
Regarding the direct to patient or the patient education, so we've been educating patients already, but our efforts through more of a direct reach out, DTC perspective, et cetera, you know, those are just about to get started. And I think that it is really important. It's really important when you have a disease that is not well understood, a disease that is not well recognized by many, but a disease that has very serious consequences. As I said, number one cause for liver transplants for women in the United States, staggering statistic. We believe that patients have to be educated, and we believe by activating the patients that are already diagnosed, and let me be crystal clear on that, our efforts are gonna be directed towards the 315,000 patients that are already diagnosed.
Having them educated and activated will be important for the field, I'd say, to better be able to treat NASH and for patients to be able to get access to Rezdiffra. So those efforts are kind of ongoing, but they're really starting in the near future. And we expect those to be helpful and certainly provide a source for patients to learn more about the disease and learn more about the product.
Tina Ventura (Head of Investor Relations)
Thanks, Jay. Luella, next question, please.
Operator (participant)
Our next question comes from Prakhar Agrawal with Cantor. Please go ahead.
Prakhar Agrawal (Managing Director and Senior Biotech Analyst)
Hi, good morning, and congrats on the quarter and the launch. I have just one. So what are you hearing on what payers and physicians will require to track response for Rezdiffra at 12 months and beyond for reauthorization? Specifically, will stable patients on Rezdiffra will be reauthorized, or only patients who show some improvement on non-invasives? Thank you.
Bill Sibold (CEO)
... Yeah, Prakhar, thank you very much for the question. You know, yeah, we are hearing that there are kind of a reauthorization period at around 12 months, and that's typical, right? For specialty products, you have a reauthorization at that point. It varies, but as you said, it's either, you know, stabilization or improvement. You know, we're still 9 months away from the first patient actually going through that or so, 10 months, what, 8 months, whatever it is, in that range. And you know, that's something. The policies are where they are today as well. We think that they're reasonable, but if there's any that aren't, you know, we have between now and that period of time to continue to talk to the payers about them.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
You know, what we're seeing, for instance, with the expert recommendations that recently came out in Clinical Gastroenterology and Hepatology, you know, they talked about kind of 3 stages. They talked about identifying a patient, taking a look in measure what's happening with the patient, and then at 12 months, looking at efficacy, and we think that's right. We think that a 12-month look at efficacy is the right time, because you have to remember, with fibrosis, and the FDA said this in their press release as well, that, you know, to have seen an effect that we did at 52 weeks was really early, they thought, because fibrosis is such a, you know, a significant hurdle to overcome.
So, you know, we think that we're very comfortable right now with what the policies say, and we're comfortable with the expert recommendations that have been put forth as well.
Tina Ventura (Head of Investor Relations)
Great. Thanks for the question. It's 8:45. We're at the mark, so let's, we have time for one more question, Luella.
Operator (participant)
Our next question comes from Jonathan Wolleben with Citizens JMP. Please go ahead.
Jonathan Wolleben (Managing Director and Senior Equity Research Analyst)
Hey, thanks for squeezing me in. Just one. Bill, you mentioned kind of the path to peak sales a couple times in your prepared remarks. Wondering how you're thinking internally what the peak opportunity is for Rezdiffra, especially now when you're thinking about full economics in Europe. Thanks.
Bill Sibold (CEO)
John, it's a great question. Thanks for, thanks for calling me out on that. And I'm not gonna tell you what we think peak is right now, other than, you know, look, I think you look at the market dynamics. We said just US alone, there's about 315,000 patients. Any way you start to look at, you know, where this ends up penetrating to, and it's a specialty category, this becomes a specialty-like category. I mean, NASH, overall, we're talking about $ billions, and as the product that has, I think, a durable profile, when we look at any information that's presented at EASL, you know, we don't think anyone is even as good as us. And none of them are pills.
Akash Tewari (Managing Director and the Global Head of Biopharmaceutical Research)
And, you know, I'll tell you, you ask patients, especially these patients, they have a lot of other stuff that they have to take. A pill is a lot easier to add than you're gonna add another injectable to my regimen. Some of them don't make you feel that great either, and you still got to stay on something for a long time. Now we haven't, you know, you know, we're still working on what the total opportunity is from a EU perspective, and then clearly from an F4 perspective, that that opens things up. So I know that's a lot of, a lot of talking without giving you the number that you want. But look, we're. I think any way you look at it, this is a big specialty category, and we think that we are in the lead position now.
We think that we will be in the lead position for a long time because of not only the product, profile, but the comprehensive data set that we've generated and we're continuing to generate. We are gonna be a long way ahead of anyone who's even next to us.
Tina Ventura (Head of Investor Relations)
Great. Thanks, John. And, thank you all for your time today and your interest. This now concludes our call. A replay of this webcast will be available on our website in about two hours. Thank you so much for joining us.
Operator (participant)
Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.