Madrigal Pharmaceuticals Inc
NASDAQ:MDGL
If you don’t study any companies, you have the same success buying stocks as you do in a poker game if you bet without looking at your cards.
Utilize notes to systematically review your investment decisions. By reflecting on past outcomes, you can discern effective strategies and identify those that underperformed. This continuous feedback loop enables you to adapt and refine your approach, optimizing for future success.
Each note serves as a learning point, offering insights into your decision-making processes. Over time, you'll accumulate a personalized database of knowledge, enhancing your ability to make informed decisions quickly and effectively.
With a comprehensive record of your investment history at your fingertips, you can compare current opportunities against past experiences. This not only bolsters your confidence but also ensures that each decision is grounded in a well-documented rationale.
Do you really want to delete this note?
This action cannot be undone.
| 52 Week Range |
171.37
354.85
|
| Price Target |
|
We'll email you a reminder when the closing price reaches USD.
Choose the stock you wish to monitor with a price alert.
This alert will be permanently deleted.
Madrigal Pharmaceuticals Inc
Earnings Call Analysis
Q2-2024 Analysis
Madrigal Pharmaceuticals Inc
In the second quarter of 2024, Madrigal Pharmaceuticals reported a robust launch for Rezdiffra, generating $14.6 million in net sales and securing over 2,000 patients under treatment. The company noted that significant efforts have been made to reduce the time it takes to fill a prescription, moving from an initial 60 days to approximately 30 days. This improvement is attributed to streamlined processes involving physicians, specialty pharmacies, and payers. Payer coverage has also shown encouraging progress, with more than 50% of commercial lives covered, and the aim is to reach 80% by year's end. This early success underscores strong demand and effective operational strategies.
Madrigal Pharmaceuticals maintains a robust financial position, with $1.1 billion in cash and marketable securities as of June 30, 2024. The company is strategically positioned to support the multi-year launch of Rezdiffra. Research and development expenses for the quarter totaled $71.1 million, while SG&A expenses significantly increased to $105.4 million, corresponding to the scale-up of commercial operations. The favorable gross-to-net ratio this quarter was mainly due to lower-than-anticipated co-pay assistance.
Madrigal is deeply focused on establishing Rezdiffra's market presence. The company's strategy includes targeting top prescribers and aiming for comprehensive payer coverage. Approximately 20% of targeted prescribers have already written Rezdiffra prescriptions, reflecting a penetration level aligned with blockbuster launches. The company is also gearing up for direct commercialization in Europe, pending EMA approval expected next year. This expansion is predicted to further solidify Rezdiffra's market position and tap into significant unmet needs across multiple geographies.
Looking ahead, Madrigal Pharmaceuticals expects steady growth in patient numbers and prescriber participation. The company remains optimistic about Rezdiffra's potential to become a blockbuster drug, driven by its unique profile and strong demand. With the successful groundwork laid in the early stage of the launch, efforts are now on ensuring smooth prescription processes and broader physician engagement. Additionally, the anticipated approval for Rezdiffra in cirrhosis patients could substantially expand the market, reinforcing the rosy outlook for future sales and market penetration.
You don't have any saved screeners yet
Good day, and thank you for standing by. Welcome to the Madrigal Pharmaceuticals Second Quarter 2024 Earnings Conference Call.
[Operator Instructions]
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.
Thank you, Loyola. 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 will 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.
And with that, I will now turn the call over to Bill on Slide 3.
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 4 months into what we expect to be about a 12-month process. This is our #1 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. In addition to the untapped opportunity in the U.S., 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 a 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 #1 driver of liver transplants for women in the United States. They also recognize the clinical benefits of Rezdiffra for F2/F3 patients and that noninvasive 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 their 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 prescriber 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 3 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 noninvasive testing of patients. That's been paying off with favorable risk different coverage. And for patients, we're continuing to educate them on NASH and Rezdiffra while helping them navigate through the complexities of the health care system to support their treatment journey.
So 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 6. We have been evaluating our Europe strategy following the submission of our marketing application earlier this year. We expect an EMA decision midyear 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 III clinical trial. We have 125 trial sites in Europe. We formed strong relationships with the NASH European community through our clinical development program and on-the-ground presence with our European medical affairs team. And 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 III clinical trial.
We are starting to build the infrastructure now to commercialize Rezdiffra in Europe in 2025. Another key aspect of our life cycle 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 noninvasively 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 3 years. And 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 accept 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 in U.S. expert panel recommendations endorsed 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 at the commercial level, including a full field team ready to support the launch on day 1.
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 ship 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 the 1/3 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?
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 to 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've 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. We continue to anticipate a relatively steady level of R&D expenses for the rest of the year.
SG&A were $105.4 million comparted 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 30, 2024, stood at $1.1 billion, which is slightly higher than what we reported last quarter due to the closing of the green shoot from our March public offering and proceeds from option exercises. With our strong cash position, we are well resourced to support a successful multiyear launch of Rezdiffra.
I'll now turn the call back over to Tina.
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. Loyola, if you could open the call.
[Operator Instructions]
Our first question comes from Thomas Smith with Leerink Partners.
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 is due to underlying patient demands and prescriptions being built versus how much of that was related to initial inventory and stocking.
Great, Tom. Thanks. Mardi?
Yes. Great. Tom, great question. How we're going to characterize the demand versus inventory and 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 had a nice result for the quarter. However, we just want to reiterate that the typical days on hand for inventory, moving forward is 2 to 4 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 1/3 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. And I'll just make one other point that Bill made very clearly that looking forward, we had nice progress into our launch quarter and that we'll steadily add both patients and prescribers as we move forward.
Our next question comes from Andrea Tan with Goldman Sachs.
Maybe just given the focus on the launch cadence here. I just wondering if you're able to provide an update on patient numbers exiting July. I know you have over 2,000 as of the end of the quarter. And then what proportion are on paid drug?
Thanks for the question, Andrea. Look, we're not going to 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 continue to see through July. As it relates to free drug, 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.
Our next question comes from Akash Tewari with Jefferies.
This is Amy on for Akash. 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 in the covered lives, are these mostly Medicare?
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 -- those were the stats around it. Regarding the uptake, 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 1/3 away or about 1/3 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 talked about the 12 months through Q1 of '25. And 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 will be able to move through practices, both from an identification and just ease of ushering them through the whole process.
Our next question comes from the line of Andy Chen with Wolfe Research.
Congratulations on the quarter. So if you can remind me based on your market research among the 315,000 patients, what percent of them are GLP-1 experience. 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 the requirement right off the bat?
Patient experience, Andy? Or do you say physicians have experience with GLP-1s?
Oh, a patient experience like pay in the past, they have used it yes.
Yes. Look, we're seeing -- we're hearing from practices that there's more patients that have been exposed at some point with 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. I'll remind you. However, we're certainly hearing that more patients are being exposed to GLP-1s. Question always 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. Regarding payers, we haven't seen anyone requiring a step-through GLP-1.
Our next question comes from Eliana Merle with UBS.
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 uptick in -- or uptick in prescribing from the gastroenterology segment.
Yes, Eli, thanks for the question. So I mean, look, it makes sense that hepatologists are going to 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 hepatologists get started a little quicker. Now the gastroenterologist, there's a lot more of them than hepatologists. And they're working through their practice dynamics as well. As you know, there's a 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 they are at different stages of how do they actually process a patient through, 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 that's what we're spending time doing is working with them.
Now there's a lot of gastroenterologists that are writing. 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.
Our next question comes from Yasmeen Rahimi from Piper Sandler.
Team, congrats, really on a solid quarter and all the great work. I guess you commented now that you're thinking about for 2025 into expansion into Europe as well as into cirrhotic patients. Could you maybe think about is your plants 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 a partnership that could allow them to commercialize and you could focus on the U.S. So I would love sort of for you to maybe think about how we should be thinking about that just because its own caveats involved in Europe. So would love being out like are you fully committed? Do you want to partner? What are your thoughts are there?
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 that 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 doing that? What we did here is with the whole leadership team is we've built the right team and put them in place so that they could execute to do what they know what to do. But that's the same thing that we're going to be doing in Europe.
We will be very focused, targeted in the way that we launch, likely starting point is Germany. And 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. There's real excitement in Europe for the drug. And I would say if I look back a year ago, though I wasn't here exactly a year ago, but a year before approval in Europe versus the U.S.
In the U.S., 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 going to take action, they really meant it. They were waiting until the product was approved. In 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 we think that Europe as well as the 125 trial sites that we've had there is quite experienced with [indiscernible] Rezdiffra is excited about it. But we are going to 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 above that launch.
Our next question comes from Liisa Bayko with Evercore ISI.
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?
Liisa, thank you very much for the question. Let me start just 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 there are clearly, we're seeing steady additions to patients. And as I said, prescribers throughout the quarter and since the quarter. Maybe from a gross to net perspective, Mardi, I'll have you.
Yes, absolutely. Thanks, Liisa, for the question. So our second quarter or first quarter of launch gross 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 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.
Our next question comes from Ritu Baral with TD Cowen.
I wanted to ask a little bit more about the prior ops 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.
Well, thank you very much for the question, Ritu. We are not seeing access to any of the NITs as being problematic. In fact, we're obviously 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 the ELF and FIB-4 from a blood test perspective. So 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? No. But we're at the very beginning here. And as I said, as it relates to NITs, I think it's going to be a 3-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 going to take a few years before there is just real -- well, there may never be alignment, but I think that there's going to 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, the big concern out there was our biopsy is going to be required and that just has not been the case. We talked about less than 5%. And now 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 talk -- 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 going and trying to find a high-priority patient. And that's what takes the time here to get us to that steady state.
Our next question comes from David Lebowitz with Citi.
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 assume that it's in between 30 to 60 days, this point actually already reached 30 days or potentially is exceeding 30 days.
David, thank you for the question. And maybe just a little bit of context first, is as we were out starting to 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 we've been clear from the beginning, saying that we won only F2/F3 patients and that's been a 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 team is 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.
I think it's also an acknowledgment that the payers see the unmet need and they don't want to 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 not good. So that's how 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 in time. They didn't want to 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 days than to 60 days, 60 days...
Our next question comes from Ed Arce with H.C. Wainwright.
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?
Ed, thank you very much. Gee, I don't have the list in front of me of the payers, and we're not going to 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 in a lot of cases from patients and advocacy. 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.
So we would expect over time that those discussions will take place. And we're hopeful that those plans will come around. But remember, we always said that there'd be outliers and as just as we said, there are some outliers out there that are requiring biopsies. So we'll keep working at it. 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 noninvasive tests.
On the COGS question, I'll turn that over to Mardi?
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 another -- for about 1.5 years to 2 years from this point, really depending on [indiscernible] on the top line, of course. One thing I would note that 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 medicines. So COGS for Rezdiffra is going to be quite low.
Our next question comes from Jay Olson with Oppenheimer.
Congrats on the launch progress. 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.
Jay, thanks for the question. On the split of F2 and F3, it's pretty even. I think if you were to ask physicians who would they rather start with, they prioritize the patient and say, we probably want to 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 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, I don't have any real insight into that. 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 -- is there some -- 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 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. 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, #1 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 going to be directed towards the 315,000 patients that are already diagnosed having them educated and activated will be important for the -- I'd say, the field 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.
Our next question comes from Prakhar Agrawal with Cantor.
Congrats on the quarter and the launch. I have just one, 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?
Prakhar, thank you very much for the question. Yes, 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 stabilization or improvement. We're still 9 months away from the first patient actually going through that or so, 10 months to 8 months, whatever it is in that range. And 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 -- we have between now and that period of time to continue to talk to the payers about them.
What we're seeing, for instance, with the expert recommendations that recently came out in clinical gastroenterology and hepatology. They talked about kind of 3 stages. They talked about identifying a patient, taking a look in after several months as to 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 to have seen an effect that we did at 52 weeks was really early they thought because fibrosis is such a significant hurdle to overcome.
So 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.
Our next question comes from Jon Wolleben with Citizens JMP.
Just one. Bill, you mentioned kind of the pack peak sales a couple of times in your prepared remarks. Wondering how you're thinking internally what the peak opportunity is for us defer especially now when you're thinking about full economics in Europe?
Jon, it's a great question. Thanks for calling me out on that. And I'm not going to tell you what we think peak is right now other than, look, I think you look at the market dynamics we said, just U.S. alone, there's about 315,000 patients. Any way you start to look at 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, we don't think anyone is even as good as us and none of them are pills. And I'll tell you, you ask patients, especially these patients, they have a lot of other stuff that they have to take. Pill is a lot easier at then you're going to add another injectable to my regimen and 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 -- we're still working on what the total opportunity is from an EU perspective. And then clearly, from an F4 perspective, that opens things up. So I know that's a lot of talking without giving you the numbers 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 going to be a long way ahead of anyone who's even next to us.
Thanks, Jon. 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 2 hours. Thank you so much for joining us.
Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.