Q - Georgi Yordanov
So I guess, to start, maybe we can just started with kind of like taking a step back and thinking about the European opportunity. Obviously, that is something that we at Cowen have for a long time being big believers in obviously, you're too. So maybe, can you can you help us frame that opportunity, the size of that market? And how should we be thinking about it?
Karim Mikhail
Sure. So the you know, the opportunity in Europe and internationally is really why most of us join Amarin, by the way, in the last two years is, because the company was at a time where we're losing the IP in the U.S., we understood how big that is. But we also knew from prior experience that we can recreate this potential in Europe and international.
So when you look in Europe, for example, you're talking about, you know, another 14 million statin treated patients, so not very different from the numbers in the U.S. If you look at how many of these, you know, have elevated triglyceride, more than 150 is probably a third. How many of these have established CVD, you can discount another 20%. So we're still talking in the millions of patients of patient potential in Europe. So it's definitely a very significant opportunity.
Georgi Yordanov
That's great. Your next question, maybe will be helpful to us, especially U.S. centric analysts is what is normal for a launch? What should we be expecting in terms of timelines? And as you know, whatever we've said in the past, or wherever we weren't, now we are here in from this moment, how would you frame out expectations and what it takes to get a product established and kind of going in a ramp?
Karim Mikhail
Yes, and the challenge here is, obviously Europe is very different than the U.S. Because what we're used to in the U.S, the minute you get the approval, you have the product ready, you launch immediately, you have your early managed care contracts in place, and you start selling the next day. And what happens is in two, three years, you start getting into the rebating, and the prior authorizations, because you sold a lot, the opposite almost happens in here.
So you take around maybe two years, on average, I'm saying in terms of pricing, reimbursement negotiations, depending on the country. But once you have that you basically have open, unrestricted access to the eligible patient population that you agreed upon. So you no longer go back to ask anybody for anything. A prescriber prescribes the patient fulfils its paid. And that's it. And you will literally have that for the life of the product, unless you have a price revision at Tier 3 or Tier 5.
So the pricing reimbursement Europe is the most critical gate to basically go through, when you have that at the right price level. You really built already 70%, I would say of the value of the product, because after that, it's a penetration issue. It's how good are you in getting physicians to prescribe. Now, we're talking about a very different prescriber base than the U.S. statin treated physicians in the U.S. like 700,000, right?
These are not the numbers you're dealing with in Europe, even in a country like France that has 70,000 GPS, you end up visiting 13,000 if you have the largest Big Pharma field force, why because the business is very concentrated. So you can actually be far more efficient at the European level. But still, it's a process that takes time. You cannot go from I have a label to pricing reimbursement next day to you're getting to your peak within just a few months.
Georgi Yordanov
And just another broad question before Georgi starts drilling down on some of the specifics. Remind us who you are, what you've done, because you just framed out Europe and we're talking Europe, so it'd be great to your background. And so we understand, you know, your expertise as you as we go into this launching attendee executed?
Karim Mikhail
Yes, so I'm a pharmacist by training. Most of my career, I have 22 years with Merck and company, lived and worked in seven different countries across three continents. My last three roles at Merck were, you know, Head of Global cardiovascular business, so U.S., European International, but before that Chief Marketing Officer in Europe and CEO of emerging markets so a third of my life in the U.S, a third in Europe and a third in international markets.
And throughout my career in the cardiovascular alone, we launched the ezetimibe franchise, we launched JANUVIA, JANUMET. We launched Cozaar, Hyzaar. And I even you know, even worked on Renitec in its latter days and it is great for me and for all of us to be working on a drug like the CPAP. I mean, it is not every day that you see a product delivering not 25, because in Europe, we are mostly on established at 30% relative risk reduction, three, zero.
Georgi Yordanov
And you know some of the things that is the evolution of launching a drug in the U.S. 15 years ago and 10 years ago and five years ago, and right now there's been an evolution payers are much more important. Is Europe a little bit more static, meaning what's happened 10 years ago and five years ago is fairly similar today, or there have been some nuances and differences you'd have to adapt to?
Karim Mikhail
It's been very dynamic. This is a very good question. Not only there have been changes in the last 10 years, there have been significant changes in the last two years. Why? People maybe forget that, you know, in Europe, medicine is paid by the government, right? Everything is subsidized by the government. There are no private insurances, right? There are no contributions that you pay to an insurance company.
It's deducted from your salary with your tax, your social contribution. And the government takes that money and basically pays us the pharmaceutical companies for the drug. So you're really negotiating with the government, one single payer, on you know, the future of your drug. And the challenges in the last two years, is that most of these governments have been under incredible budgetary pressure, where a country like Germany.
And you know, we've had a challenge in Germany, like many other companies, they've basically had a healthcare deficit that they've never had in 20 years. So it was not possible no matter even if you had the miracle drug, for them to say. Yes, I will reimburse because they just don't have the money to pay for it. It's as simple as that. It's not a privately regulated system.
Georgi Yordanov
That's great. So maybe, can you can you remind us how many countries in Europe is have the reimbursement negotiation being completed, and then how many have you launched in?
Karim Mikhail
So when we started 2022, we had only one country in pricing, reimbursement negotiation, we finished 2022 with 10 submitted doses and five approved. So we have now the product price available and in launch phase in the U.K., in Sweden, and Finland and Austria and Denmark. And our price in those five markets is very similar, in the range of €5, €5.3 per day, almost $2,000. Net a year, which is completely in line with what we committed to that we believe there is significant value in terms of revenue.
Very recently, we compare this price with the average cardiometabolic in Europe, larger patient population in Europe you tend to get a very low price per day, because the patient population is huge. So far, what we have achieved is very positive. Now we are in markets where we have even larger population. But where we started allows us a bit of room to negotiate. So that's the phase we're in.
Georgi Yordanov
Great. And - I guess, what are the expectations in terms of by the end of the year in terms of launches in Europe? And can you frame maybe the number of countries you're in right now, what percentage of the market is that? And where do you get where do you expect it to be by the end of the year?
Karim Mikhail
So 2023, we believe is going to be the year where we're going to have most of our pricing reimbursement decisions completed, right? We're already in launch mode in the U.K., this is now the key focus. And in 2023, let's face it, the revenue is going to come mainly from the U.K., because it will be the only country that had 12 months of revenue, other markets as they come they will contribute to the revenue.
But as we always say, you know, the easiest thing in Europe is to say let's accelerate, the negotiation, they give us a price and we say yes. Well guess what, if this is a, I'm just making a number 20% discount. You agree to that you agree to it for the next 10 years. We have regulatory exclusivity until 2031. So imagine, by giving 20% of the price you would give 20% of the area under the curve.
That's why the wise decision is always take more time to negotiate, because that price point will always be better than just making a concession to look good that you're rushing to market it's always better to keep the price as high as possible, because they only go lower in Europe not higher.
Georgi Yordanov
That's great, very helpful. And as we think about the U.K. specifically, can you can you provide your recently provided some updates in terms of early uptake or the feedback availability? Can you can you share any additional insights and, and again, as you mentioned, like probably 2023 European revenue will be coming from the U.K. so what percentage of that total opportunities is - does the U.K. represent?
Karim Mikhail
Sure, I'll start with the sort of last part of the question. So any large market in Europe, like U.K., Spain, France contributes generally, somewhere between 10% to 15% depending on, how successful you are, so if you add them all up, that are going to be like 60%, 50%/60% of your total, and then the mid small size, they will contribute the rest. So the U.K. will probably contribute more than 50% of the revenue of this year based on what we expect.
How we're doing, we feel very confident of the launch. So far, we've recently shared, at our earnings call, some data that shows compared to bempedoic acid and inclisiran how are we doing with formulary listing. This is another thing that again, for U.S. investors and U.S. analysts is very different. In the U.S. once you agree on a contract the product is in and there is nothing else to do. There are different health systems in Europe.
And again, I hope we're not trying to paint a more complicated picture, because we don't want to scare anybody. But this is that environment. And it has advantages and disadvantages. The advantages are in the U.K., you need to be funded, which in our case, we are funded with no discount, we are one of the very few products on the market, where we demonstrated the value, and we were not required to reduce our price.
Okay, so that's number one. But then you need the formularies of the key accounts to list you. So there is a discussion to convince them of the value of your drug. So imagine we compare ourselves with bempedoic acid, we compared ourselves with inclisiran. That's the data that we shared a few days ago. And in the case of bempedoic acid, it's an LDL reduction. So the concept is quite simple, right? People would accept to list you right away.
Inclisiran was an NHS driven deal with Novartis, meaning they discounted the price so much to agree with NHS, that they're going to fund this for 300,000 patients. So theoretically, you can be listed on any formulary right away, because the government is saying I'm pushing for that. And in both benchmarks, we actually were better than bempedoic acid as good as inclisiran, if not better, and that shows that the team on the ground in the U.K. are doing a wonderful job with the early access.
Now we need to turn this into prescription the product is available, the product is going to be paid for by the key accounts. Now it's a question of convincing physicians, challenge we had, if you remember, REDUCE-IT was not implemented. We did not have sites in Europe, with the exception of the Netherlands and Ukraine. So in many of these countries, the physician does not have any hands on experience.
When we launched REDUCE-IT in the U.S., there were five years of pre-marketing before that. So it's definitely taking time to get the product up to speed, but we feel very confident of the future.
Georgi Yordanov
That's great. And if we think about the formularies, do we have an idea of like, what percentage of the formulary you're in?
Karim Mikhail
Yes, so now we have 19 out of the top 20. Okay and that covers 50% of the eligible patient population already. And we are not even, you know, three months after launch, where we have open availability to half of the market. And again, we've shown data that says, Who can prescribe within that account, because these are important details in Europe at times, especially in countries like Italy.
You have the product available, but it's restricted prescription for a number of physicians. What we got in the U.K. and all these accounts is at full open 100% prescription capability for anybody, GP cardiologist, endocrinologist, first intention, second intention, repeat or new. So that is also a great thing.
Georgi Yordanov
And it's just a matter of time to get to 100, rather than there is more?
Karim Mikhail
Yes, but we already have - we already have, honestly the big bulk of it. Now it's a question of driving awareness, building the adoption and making sure that the prescriptions.
Georgi Yordanov
That's great, so maybe that's actually a good segue to the next question, which is, how - can you talk about how prescribing for an indication like, was - is approved for how - might it differ from the U.S. in Europe, in terms of the specialties of clinicians?
Karim Mikhail
So, it depends on the country, right? There are countries that are very well known to restrict prescription to specialty. So in Italy, for example, it's a country very well known to restrict to specialists at launch. They'll keep you there for a year or two, just to make sure that actually the product is not misused. It's not like they don't want you to sell. They want to make sure that the product is going to be used appropriately.
So they say you're going to be with cardiologist for a year or two, and then we're going to open it up for GPs. In the case of the U.K., we don't have any restrictions on prescribers. In the case of Sweden, Finland and all these other markets, we do not have any restriction on. But we are reimbursed for established CVD patients not for the primary prevention patient population.
Georgi Yordanov
And your current sales force, what percentage of I guess of the total opportunity do they have access to?
Karim Mikhail
So, we currently have a small specialty team in the U.K. Because of the way we sequence the plan, we've been incredibly cost/cash conscious, as we're launching. So we did not go with the approach of let's always go with the big guns, and let's throw all the money we have, because in Europe that actually doesn't pay out. What you need to do is you build, you step on what you build then you go even higher.
So, we currently have a small team targeting cardiologist, endocrinologist and key clinicians. But we feel very confident with what we have at this point in time and at the right time, we will expand obviously.
Georgi Yordanov
That's great. And I guess, thinking about the launch, and how we could, I guess, track or set expectations, what we kind of like started the questions about? Are there any, I guess examples of European launches that could be helpful to investors, it's usually very helpful to kind of have a comp and kind of get an idea of like, what has happened before? How can we think about it now, obviously, the unique every situation is unique?
Karim Mikhail
Yes, every situation is unique, your right again, and this one is even more unique, right? Because there are so many - you could say, oh fibroids could be a good competitor. But fibroids don't have a cardiovascular claim, right? They've reduced triglyceride, but they don't have a cardiovascular risk claim. So there are a number of ways of going about this. First of all, this is a product that's going to be used on top of a statin.
So the most logical thing is for you to look at products that are used on top of a statin what is used on top of a statin today, ezetimibe is used on top a statin PCSK9, are used on top of a statin. Unfortunately, for those two there are, you know, disadvantages of looking at them as ezetimibe is 15 plus years old or more. And PCSK9 are injectable, and very expensive. So they will provide some value, but not so much.
So we also add to the mix products that have a cardiovascular risk reduction, like some of the anti-diabetics like some of the anti-platelet products. So hopefully soon for the U.K., we will be able to share some of this data just to compare and contrast. How are we doing with others? The challenge with these comparisons is that we show revenue data based on list price. And we are the only product may be on the market that does not discount.
So we're going to be disadvantaged compared to everybody else, but I still believe we're still going to look, you know, better than expected so, looking forward to share this data late this year.
Georgi Yordanov
That's great. And have you provided any guidance in terms of what our expectations should be for ex U.S. sales this year?
Karim Mikhail
So, I want to say we, we would be probably the party that is most excited about sharing guidance, right? We've been working on these numbers ourselves for the last three years, you know, what is Europe going to sell and by year and so on, we have a very, very robust model. We already said that it's going to be above a billion. Our challenge in the negotiation is imagine you are negotiating with the Spanish government.
And at the same time, you're going publicly to say, here are going to be my revenues by year over the next whatever five years, while you're actually negotiating with them, potentially a volume price deal. They're going to see these numbers. That's not how you do things, right. And remember, there is no pharmaceutical company in general, that gives guidance about Europe, right, especially when you have one product, because it puts you at a very risky position.
Now, having said that, we are very keen on communicating guidance, we want to communicate guidance, because we want to show what you know what to expect for an investors, but we really want to wait until we have the big markets negotiated. So that's, you know, Spain, Italy, France, to make sure that we have this and then at that point in time, it would be more logical to share some of this data.
Georgi Yordanov
That's great. So a lot of progress maybe. Can we talk about Germany, specifically, is there a chance we can revisit that opportunity? And then if we don't, what percentage of that market? I guess we won't have access to show?
Karim Mikhail
So back to Germany, and we just discussed a few minutes ago, what has happened in Germany, why we are where we are and we passed through a phase where nine out of 10 products in Germany got no additional benefit. And that was not because of anything related to the drug that was something related to their, own budget and what they're able to pay. So to rush today to Germany is useless, because the situation the economic situation has not changed in Germany dramatically.
So to go and try to renegotiate now doesn't make sense. So step number one is get the other markets approved, show Germany, that they are singled out, by the way, historically, they've been singled out many times. And they don't get sort of ashamed of that so, but make sure that there is Pan European endorsement of your price level, that's number one. Number two, start working on your resubmission.
Because you need to come back with different data, you need to come back with a different approach, which we're working on. But very recently, you have read maybe in the news that there, have been a very historical litigation in Germany, you know, a company that actually challenged the German system and said, no, no, you miss actually judged me. And this is the first time in German history and they won the case.
And that case has similarities with our product, not 100%. There are similarities, the similarities are this was a product that did not have a clinical competitor. In our case, we also did not have a clinical competitor. So, we definitely are going to explore, you know, avenues of using that it is still too early to judge whether this is going to be a viable solution or not. But this is a team that does not give up, right? So we're going to keep trying to go back to Germany, because it represents 10% to 15%, of potentially European revenue.
Georgi Yordanov
That's great. And thinking about outside of the EU, can you help us define that opportunity? We saw recently, the deal we signed, which provided some small non-diluted funding, or can we can we expect some tax similar in the future?
Karim Mikhail
Yes, so - remember, this is an initiative that started in August 2021, right. So in August 2021, where we basically said, we are available in Europe, we are available in the U.S., but there are so many other important markets beyond U.S. and Europe. And we initiated the process to get regulatory approval in 20 additional countries beyond U.S. and Europe.
Some of the early approvals that we got was in Australia, and by the way, Australia participated in the REDUCE-IT study. So it is a country that has hands on experience with a number of sites that was implemented there, where we have regulatory approval today, and you've seen us, communicating that we have a partnership there. So this is a very active program.
We have the deal with CSL Seqirus that we're very, happy with, they're the ones who introduced, you know, the Moderna vaccine to Australia, so a very robust, reimbursement/commercial team. And - we also made comments that we are working on potential partnership in Southeast Asia and Eastern Europe that we - are ready to execute in the near future. And the size of the opportunity to your question is significant.
And I remember that you had some of your own sort of analysis, showing that for a product like Lipitor, the split between us and ex, U.S. revenue was 50:50. And when you look at that splits, you'll see that the 50, that's ex U.S. and imagine, the potential for the U.S. business for the VASCEPA was somewhere between the three to five, right? Imagine if you can recreate that ex U.S.? Well, two thirds of that are going to come from Europe, and one-third is going to come from rest of the world.
And I believe these data on Lipitor, did not include China as part of them. But definitely the opportunity, the magnitude of the opportunity ex U.S. is significant and can be in the cardiometabolic space as big as the opportunity in the U.S. It just takes time to build it and to develop it over time.
Georgi Yordanov
Now that's a very good point. And I believe the specifically for Lipitor, didn't have to take some pretty significant discounts on their pricing in Europe?
Karim Mikhail
Yes.
Georgi Yordanov
So opportunities even larger, you've talked in the past about franchise extension strategies for VASCEPA and specifically combinations with statins. Can you provide - an update on that?
Karim Mikhail
Sure. So first of all, we feel very strongly about the value of fixed dose combination within the cardiometabolic space. If you were at European Society of Cardiology, the last conference, there was a whole session about treatment strategies. And it was all about fixed dose combination. It was about how can, you use multiple products to just help the patients. For us we're introducing a new paradigm of treatment in Europe.
If you can somehow associate yourself with a non-molecule that's used loved, on daily basis, that just gets you to gain years of adoption, right, instead of just going it alone. You put yourself with a strong statin then very quickly you become a far more familiar product. Now on top of that, you get potentially, a better lifecycle management strategy, because it allows you to continue to penetrate allows you to negotiate price at the right time.
Meaning that your price revision time-point three, five years, you go to the European government, and you say, look I have a deal. I'm going to give you the statin for free, if you don't actually impact my price, and you keep going. So instead of get a price erosion, you keep that price increment, imagine if this was only 5%. And imagine if that 5%, you are going to get three times until you lose exclusivity.
Three, multiply by five compounded it's like 17%, 18%. That's a lot of area under the curve, to create. So we feel very strongly that this is an opportunity, you saw that we communicated that we submitted to EMEA. For advice, we got back feedback, we're working on our response on this, and we're going to continue to pursue it. This is a challenging initiative. Let's be very clear, it's not that easy to put and oil with a solid in one product, right.
So there are formulation challenges, there are potentially stability challenges. So, we don't want anybody to think oh, this is going to happen anyway. No, no, this is a challenging initiative, but it's worth pursuing. It is worth pursuing. And all the larger franchises have fixed those combinations ezetimibe had four Cozaar had two, JANUMET had one. So many, many of the franchises have that.
Georgi Yordanov
Okay, why don't we wrap it up there Karim. Thank you, for taking the time, all the best to you and your team as you continue to execute the launch and enjoy the rest of the conference. Thanks.
Karim Mikhail
Thank you.
