Hello, and welcome to Ipsen's conference call and webcast on the year-to-date sales performance. I'll now hand you over to David Loew, Ipsen's CEO.
Thank you, operator. Good afternoon or good morning, everyone. Welcome to Ipsen's year-to-date sales update. I'm David Loew, CEO of Ipsen, and it's my pleasure to take you through our sales performance in the first nine months and third quarter of the year. Please note that our presentation is available on ipsen.com. Please turn to slide two. This is our safe harbor statement, which outlines the routine risks and uncertainties contained within this presentation. Unless stated otherwise, any commentary on growth you'll hear today will be based on constant exchange rates. Please turn to slide three. I'm going to take you through our brief presentation, after which I'll be joined for the question and answer session by our CFO, Aymeric Le Chatelier. Please turn to slide four.
We're on track for the full year delivery of our strategic priorities, and this is illustrated by today's highlights that center on our sales growth, momentum, and pipeline progress. Total sales grew by 7.1% in the year to date, with Q3 sales up by 6.5%. Sales from the growth platform of Dysport, Cabometyx, Decapeptyl, and Onivyde increased by a combined 16.1% in the first nine months, while there was also growing contribution from our new medicines. We also made significant milestone progress in our pipeline, including with Sohonos, Cabometyx, and elafibranor, while we plan to refile odevixibat with the EMA in Alagille syndrome. I'll take you through the details in a moment. Finally, we have confirmed our full year guidance. We continue to expect total sales to increase by more than 6% at constant exchange rates this year.
The core operating margin is anticipated to exceed 30% of total sales. Please turn to slide five. Our growth platforms are continuing to perform well and are consistently outweighing the gradual decline of Somatuline. I'll now take you through our sales performance in more detail. Please turn to slide six. Turning to the growth platform's performance in Q3, Dysport sales grew by 13%, reflecting a challenging baseline effect. The market, however, remains strong in both aesthetics and therapeutics, with Dysport sales up by 25% in the year to date. Cabometyx sales were up by 21% in the quarter, with strong volume growth, in particular from the first-line renal cell carcinoma combination, which is now reimbursed in over 20 markets, so shipment phasing in the rest of the world impacted the overall performance.
Cabometyx in second-line renal cell carcinoma also continues to see good volume growth, notably in rest of world markets. Decapeptyl's growth in Q3 was limited to 4.5%, reflecting the challenges in China from the impact of adverse economic conditions on market growth. We have also recently seen the majority of healthcare provider interactions canceled as a result of the industry-wide anti-corruption campaign in China. In Europe, volumes continued to perform well, though overall sales were stable, reflecting increases in the level of competitive activity. Finally, Onivyde is growing nicely. In North America, Q3 sales increased by 16% as we continued to grow share in the current setting. We also made further preparations for a potential launch of the Onivyde regimen in first-line pancreatic cancer. As a reminder, the PDUFA date is set for mid-February. Please turn to slide seven.
Somatuline sales fell by 12% in the year to date and in the third quarter. This was further evidence of its gradual long-term decline profile, as illustrated by the chart you can see. In North America, sales fell by 18% in Q3. Pricing continued to be impacted by the level of commercial rebates and adverse movements in channel mix, though our market share is holding up well. In Europe, the sales decline of 9% was less than in recent quarters, given the reduced baseline effect from Q3, as it is more than 12 months since the generic was launched in key countries. Finally, in the rest of the world, sales were up by 16%, despite the launch of a generic in Australia. Please turn to slide eight. Our new medicines made a significant contribution to our top line in the first nine months of the year.
Since completion of the Albireo acquisition in March, Bylvay has delivered EUR 46 million in sales, and we were pleased to launch recently in a second indication, Alagille syndrome, in the United States. Sales in the first indication, PFIC, were encouraging as we increased the number of treated patients in both North America and Europe. Onivyde's relaunch continues to progress, though we recognize that it will take time to convert our activities into sales growth. In the first nine months of the year, we delivered EUR 28 million of sales, with growing commercial demand as a result of increasing prescriptions in the community setting. Finally, it was great to see FOP patients finally being treated with Sohonos in the U.S. this month after the FDA approval in August, especially as it's the first and only approved treatment for patients with FOP.
Global Sohonos sales so far this year amounted to EUR 3 million, though this reflected special license sales in some ex-U.S. markets. Please turn to slide nine. Looking to the major elements of our pipeline, we reached a number of important milestones in the period. In prostate cancer, one of the primary endpoints, progression-free survival, was met in the CONTACT-02 phase III trial of Cabometyx plus atezolizumab. We await mature overall survival data. While Bylvay was approved in the U.S. in Alagille syndrome, we did not achieve orphan drug maintenance status in the same indication in the European Union, despite the positive CHMP opinion. We therefore plan to make a separate regulatory submission of odevixibat in Alagille, Alagille syndrome under a different brand name in order to retain Bylvay's orphan status in PFIC. We expect to file before the end of this year.
We have initiated two new phase III trials for Dysport across chronic and episodic migraine. We have seen that the migraine market is dynamic and growing, and therefore presents a good opportunity for Dysport. Finally, regarding elafibranor, we plan to file in second-line PBC in the U.S. and EU before the end of this year. Please turn to slide 10. So before we go to questions, please let me conclude. There are two key messages to take away from our update today. Firstly, our top line momentum is strong, driven by our growth platforms and the increasing contribution from our new medicines. Secondly, our pipeline is progressing nicely, with several positive milestones in recent months, coming ahead of multiple expected launches in the near term. Finally, I wish to confirm two dates for your diary.
Following the late breaker presentation of the ELATIVE trial results at the AASLD Congress on 13 November, we plan to host a question and answer call for analysts and investors on 14 November at 4:00 P.M., Central European Time. Joining the event will be Dr. Christopher Bowlus, presenter of the late breaker session. The other date is the Capital Markets Day we plan to host on 7 December in London. Details will be published and distributed next week. Please turn to slide 11. So thanks for listening to our presentation. Aymeric and I now have time for your questions. Operator, over to you.
Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, you can press star one and one again. Please stand by while we compile the Q&A queue. Thank you. We'll now take our first question. Please stand by. First question is from the line of Brian Balchin from Jefferies. Please go ahead.
Thanks. Just two from me. On Bylvay, can you just help us with how we should be thinking about peak sales of that now that you won't have orphan designation for ALGS in the EU? And can you just clarify, if Mirum successfully file for their phase IIb in biliary atresia in December, would that put orphan designation status at risk for Bylvay in that indication, too? And then on Somatuline erosion, can you just help us with how we should be thinking about that, just 2024 and beyond, in light of the Crinetics on daily oral paltusotine and potential impact from that? Cheers.
Yeah. Thanks, Brian. I will start with Bylvay, and on your question on peak sales, I mean, I want to defer to the Capital Markets Day, so we're going to update you on the longer term guidance there, and also talk about sales guidance on the key products. But I can elaborate a bit on the orphan drug designation. So you need to remember that, on the Bylvay forecast, the majority of sales is going to come from the United States. In Europe, there will be some delay. We anticipate an approval of the second brand mid-next year.
We are not going to be able to launch in all the countries, especially, probably Germany, because there is a legislation that if you don't have orphan drug indication for a certain drug in a certain indication, it has an impact on the pricing. So, we will stay on PFIC with orphan drug in Germany, for example, but on the orphan drug status for Alagille, that is going to probably have an impact, and therefore, we will have to see with the payers in some markets where orphan drug status plays a role in reimbursement, how we can proceed there. But the impact is not that big. So just to help you a bit with the guidance.
On your question on biliary atresia, the feedback we have gotten from the FDA was that they want to see an outcome in the clinical trial. So this is why we have reopened our phase III study, to go for native liver survival. Mirum does not have that in their phase IIb. It's hard to say what's going to happen with that in Europe. It's not totally clear there. If they would be able to file in Europe, I think it's fair to say that if we go for an outcome trial, we would probably have significant benefits and therefore maintain the orphan drug status while coming a little bit later.
But, I mean, BA is an indication where you can generate native liver survival data relatively rapidly, so we have to see what the reaction is going to be from the regulators regarding that. Then on your second question, on Somatuline erosion, specifically, regarding Crinetics, I think that's your question. So there are kind of two aspects. What's going to happen to the erosion? So we, we still continue to believe that there is going to be a gradual erosion over the years to come. It's triggered by two things. There are some more generics potentially making it to the market, but then there might also be some new drugs coming to the market, like Crinetics.
However, on Crinetics, specifically to your question, we don't believe it's going to have a very big impact because when you look at their study, it's in acromegaly, and it's stopping, you know, some somatostatin analog and switching to an oral anti compared to placebo. So, I'm not sure that this is really very convincing. So we, we have baked in some erosion for new drugs, but, on this specific one, it's probably gonna be more limited. Thank you. Next question.
Thanks.
Thank you. We'll now move to the next question. This is from the line of Xian Den g from UBS. Please go ahead.
Hey, thank you for taking that question. Could you hear me all right?
Yes.
Perfect. Thank you. So I have two questions, please, and both on Dysport. So the first one, just wondering if you could give us some colors on the aesthetic market in the U.S. and ex-U.S. region, especially considering the economic downturn. Just wondering, you know, what are, have you seen so far in terms of the trend of the end user Dysport in aesthetic market, and what do you expect in Q4 and going into 2024? So that's the first question. And the second question is related to Dysport and QM1114. So I was just wondering if you could confirm, you know, like, the geographical split and royalty, et cetera, and economics for QM1114.
Just wondering if you could confirm whether those economics are actually similar to Dysport at the moment, or they are quite different. Do you think they might actually change depending on the remaining arbitration outcome? Thank you.
Thank you, Xian. On your first question on Dysport, on the aesthetics, we see worldwide that the markets are a little bit softer, but it's still growing very nicely in aesthetics and also in therapeutics. So, it's a very attractive market still. Regarding your second question on QM, the economics are broadly similar. There might be a difference if QM would, you know, penetrate to a very, very large degree, which, when you look at Revance, we would not anticipate today. That's where we are. In terms of the geographical split, I'm not quite sure what your question is.
Oh, so it's just a split. At the moment, are they actually similar to what you have agreed with Dysport?
You mean-
Geographical split for QM1114, they are the same as Dysport. Yeah. Sorry.
Yeah, the answer is yes. Yes. Okay, thanks a lot. Next question.
Thank you. We'll now take our next question. Please stand by. This is on the line of Simon Baker from Redburn Atlantic. Please go ahead.
Thank you for taking my questions. If you'll indulge me, I have three. Firstly, on going to slide 13, you very helpfully give us some color on the currency exposure that you have, but I wonder if I can dig a little deeper and ask for some more clarity on the other portion. Particularly the approximate contribution of the three currencies that you highlight on the right-hand side, the real, the Aussie dollar and the Turkish lira. Any color on that would be quite useful. Secondly, on Tazverik, I wonder if you could just update us on how far through the mechanics of the relaunch you are on that.
And then secondly, and you did allude to this a little on the call, but some more insights would be great on the process and timing for getting access and reimbursement for Sohonos and where you currently stand on that in the U.S.? Thanks so much.
Thank you, Simon. I will defer the first question to Aymeric regarding the currency exposure.
Yeah. So regarding the currency, as you know, we are operating in many, many country. I think it's more than 40 country outside of the euro currency country and the US dollar country. You see that the major one, which are really about Brazil, about China, for sure, about Turkey is also an important country. It none of them are very, very meaningful. You've seen that the Turkish lira has significantly devalued over the last nine months. So to quantify by country is a little bit difficult. There is a lot going on, but clearly Turkey has had a significant impact. China had also some impact. And we also have a remaining business in Russia, which also, as you know, the ruble has devalued quite significantly.
Then on Tazverik, how far are we through with the relaunch? So, first of all, just as a comment, relaunches, we know that in pharma industry are very difficult. We are somewhat behind our expectations. It's linked to the fact that we had quite some changes on the field force. We have now onboarded new people. We have trained them, so we have started to deploy them. So we will see, hopefully, an effect in the coming months moving forward. The switch is also happening, you know, from a focus that Epizyme had at the time in academic centers, and we really believe that the Tazverik patients are in the community setting. And in the community setting, it's a relatively large community, so you need to go and see a lot of doctors, and they don't have that many patients.
So it's just gonna take time until patients become eligible for Tazverik and that, physicians are actually gonna choose Tazverik. So it's a, it's a bit of a work to actually get there, but, we're confident we can see, further growth on, this area also for the future. Then on, Sohonos, in terms of, reimbursement in the U.S., so we have, several patients where, prescriptions have already been initiated. They now need to get the reimbursement with their insurance, companies. That takes always a little bit of a delay, but, I think we should see, sort of a pickup, in the coming weeks and months.
Great. Thanks so much.
Next question.
Thank you. I'll move to the next question. This is from the line of Richard Parkes from BNP Paribas Exane. Please go ahead.
Hi, thanks very much for taking my questions. Just two. Firstly, on Bylvay in Alagille syndrome, just wondering to what degree you expect payer access to have an influence on prescribing, given that Bylvay and Livmarli look largely interchangeable. And I just wondered if you could update us on where you are in terms of payer access and what barriers you might need to overcome in the new indication. And then, secondly, on elafibranor, if I look at the patient numbers, the opportunity for novel branded drugs in PBC looks to be materially larger than suggested by trials of Ocaliva. And I know it's not the perfect drug, but maybe you could talk about the barriers to unlocking that opportunity and how you might be able to do better than Intercept. Thank you.
Thanks, Richard, for the question. On Bylvay Alagille, in the US, where we had the approval, we don't really see a problem with the reimbursement, so that's encouraging. So here it's gonna be a question, how quickly we can penetrate that market. We see patients coming de novo, but we also see switches from Livmarli to Bylvay, which is actually a surprise that this has started to happen so early. But these are the two sources of patients where we're getting scripts from. On your second question regarding the market, you're right that on Ocaliva, they were not able to drive so much the market size. Typically, if you have one competitor in the field, of course, it's harder than if you have two talking about this, so that's there is one effect.
But the second effect is also, of course, that they have some side effects with colitis, which is known. So, they have recently not shown that the outcome trial was positive, so perhaps there is a little bit of an opportunity for elafibranor to take some share here. In terms of barriers of detecting new patients, we know that the detection sometimes on these orphan drugs is not so easy, so we foresee that first we are gonna launch elafibranor and focus really on gaining market share as quickly as possible. Market expansion projects typically come in a phase II, and they can come from, I would say, two sources. One is, there is a question, can you treat patients a bit earlier? And the second one is, are you actually identifying enough patients or not?
We would have to probably work with laboratories on detecting them correctly when blood sample is being drawn. So that's where we stand in terms of our market expansion thinking. Thanks a lot. Next question.
Thank you. I'll now move to the next question. This is from the line of Richard Vosser from JP Morgan. Please go ahead.
Hi, thanks for taking my questions. Two, please. Just going back to Sohonos, just thinking about the patient pool that's in the US of maybe, I don't know, 400 patients or so, you know, how many are enrolled in other clinical trials, and therefore, how many are actually available to treat? And a linked question of, how is the approval gonna affect the development of the ALK2 within your pipeline? Is that gonna make it more difficult? Are you gonna have to amend the trial program at all? And then second question, just on Onivyde, maybe a housekeeping question.
You know, some recovery in Somatuline sales, but they're still very, very low, and I know there's a new manufacturing setup, but how should we think about those ex-US sales, particularly as we go into the expansion into the first line? How should we think about the growth there, but also, I suppose the growth in the US, but really thinking the ex-US at the moment? Thanks very much.
Okay. Thanks a lot, Richard. On Sohonos, so, with the published incidence rates, you know, Necker Hospital published that, and we applied that around the world because we don't see really see big epidemiological differences. You can calculate that there are roughly 450 patients that have FOP in the U.S. Out of those, we have identified, I would say, about roughly half. Then you have to deduct from those, the ones which in the label are below the age. So in our indication, it says years 8 and 10. So 8 for girls and 10 for boys, so you have to deduct about 15% of the patient pool. But then once they get older and their disease progresses-...
Some of the older patients can find themselves in a situation where their bones are already almost completely locked. So you might have to exclude a couple of patients there as well, that are not gonna be eligible for treatment. And then, of course, we come to your question. We see about 50 patients in the U.S. being in clinical trials, of which a good part in the fifth research program that we are running. We don't anticipate an impact there because we have advanced very well already with the recruitment. So we don't anticipate that this is gonna really interfere. But of course, you're right, you would have to take them away from the commercially available patient pool. Regarding Onivyde ex-U.S., I let Aymeric elaborate on this because there is a technicality on it.
Yeah. So Richard, your question on the Onivyde, as you know, this year has been impacted by both phasing impact by quarter, because we are shipping the product by batches for several countries. It was impacted by the new manufacturing setup, where we are seeing at a lower price, but we make more margin as we transfer the product to our manufacturing plant in Europe. But your question was more about the trend. So the trend, the business is pretty mature today on the existing indication. I think going into 2024, you should see a very slow inflation as our partner, Servier, is progressively securing access in different geographies. But as you know, it's gonna take time in Europe and also in some of the ex-US, ex-Europe territories.
So you should expect a limited growth in 2024 to progressively. But as you remember, we have a limited contribution at the bottom line from that partnership.
Thank you.
Thank you, Richard. Operator, next question.
Thank you. We'll now take the next question. This is from the line of Charles Pitman from Barclays. Please go ahead.
Hi, thank you very much for taking my questions. Two from me, please. Maybe just on elafibranor and its expected competition versus kind of seladelpar as this, you know, next wave of products. And, you know, I think we're all looking forward to the full data to be released next month. But could you just speak a little bit more about the kind of target patient population? And specifically, how many of these patients would need to prioritize pruritus over the broader efficacy, and how you think this is gonna kind of play a part as you produce your kind of commercial strategy, when you're placing elafibranor in the treatment paradigm. And then just secondly, if you could speak just a bit more on your thoughts around the ongoing anti-corruption efforts in China.
What degree do you think this has impacted your sales, maybe particularly on Decapeptyl, and how do you see that going forward? I mean, is this a kind of industry change, or is this something that could annualize out? Thank you very much.
Thank you, Charles. So regarding your question on elafibranor and the target population. So about roughly one-third of patients are facing pruritus. Now, you shouldn't jump the gun. I think you need to look at the data which is gonna be presented at AASLD, and I will let it stand here. And then we can discuss during the post-AASLD session and take your questions and answers there in more detail, because I think it's gonna be important to really understand the details of the data, the demographic of patients which was included in the trial. We have seen a big difference in terms of the placebo effect. CymaBay had 20% placebo effect. We have basically almost zero.
So we really need to look at the data in all the details, and then I think we can really answer your question in more detail. On your second question regarding what's going on in China, and is that gonna have a lasting effect? We have seen these kind of things happening in China in the past. They are usually relatively temporary. They typically last about six to nine months, so we anticipate that there is a slowdown of the market growth until probably around spring. After that, there might be a bit of a lasting effect by the economic situation, because sometimes patients need to pay out of pocket. So it needs to be seen how this economic downturn is gonna last going forward. So I'm not an economist, and I wouldn't speculate too much on China on this.
There are people who are better placed to speculate about that. But it's clear that the forecasted growth rates for China are probably gonna be somewhat dampened. So that could take a bit of a toll on the growth rates in China overall for the pharmaceutical industry, in my view.
Thank you.
Thank you, Charles. Next question?
Thank you. We'll now take the next question. This is from the line of Manos Mastrorakis from Deutsche Bank. Please go ahead.
Hi, thank you for the question. Perhaps it would be interesting to hear your comments on migraine study initiation. With this part, drill down on the big sales ambition for that project. What makes you think it will be competitive, and why move into this market now? And secondly, on the withdrawal of our basket , ARIA Basket trial, Mr. Aymeric, can you tell us the rationale behind withdrawing it? Unless I missed it. Thank you.
... So on your first question on migraine, we see that neurotoxins have a good uptake despite the arrival of new oral drugs. Not all patients are responding to these oral drugs. There is a segment of patients which we believe, long-term, are gonna be still treated with neurotoxins. Peak sales, we're not gonna deliver peak sales on this call. We have a Capital Markets Day. The why now, basically, you know, we looked at the migraine market in more detail, and we believe that by embarking with Dysport today, and then eventually, later on, coming with a long-acting neurotoxin, we can already open up a door on Ipsen being in that segment. And so therefore, we see it as a stepping stone.
On itself, for Dysport, it makes business sense, but it also is gonna be a springboard for the long-acting neurotoxin once we come with kind of the new generation of neurotoxins, which has a much longer action. On Tazverik, on the basket trial, we came to the conclusion that, you know, this was a, I would say, a bit going too broad for Tazverik. We wanted to focus Tazverik on follicular lymphoma, really, which we see as the main part of the business case. So it was really a question of priority setting in the portfolio management. Thank you, Manos. Next question, operator.
Thank you. We have one more question. The last question today is from the line of Delphine Le Louet from Société Générale. Please go ahead.
Yes, hello. Can you hear me well?
Yes.
Okay. Good afternoon, both of you and team. Two question on my side. The first one regarding Dysport and especially in Europe. Can we get the real underlying growth or decline in Europe of Dysport, where we restate that from the inventory level from last year? Secondly, a question regarding the arbitration. So clearly, a clarification, I guess, is needed, and especially also another one regarding the complete response letter you received on the long-acting. So can you clarify that for me to be all set on these issues? Thank you.
On the first one, Aymeric, can you take that, the underlying inventory effect, on Dysport Europe sales?
Yeah. So I think that the baseline we were talking about in Dysport is mainly related to Europe, because if you remember last year in Q2, when we did significant investment in our manufacturing site, we had to stop shipments. And we clearly did recover because the market was doing very well in Q3. So Q3 last year was a very, very strong quarter. So the comparison that you get this year, even if the level of sales is still quite significant, and we're very happy with the performance, you have a negative impact due to that very strong baseline impact in Europe, in Q3.
In the range of mid-single digits or high single digits?
Yeah, I mean, the product continued to grow double digits. So you can assess what is the shipment impact.
Okay.
On your second question regarding the arbitration, and the complete response letter of QM1114, they are not linked at all. The arbitration was about Galderma filing in their name, and the arbitrators asked Galderma to transfer the marketing authorization holding to Ipsen. Then the second question was on the testing methodology, and here the arbitrator said that since there is no specification in terms of the regulatory filing, what the IP and marketing authorization holder can say, Galderma can submit the testing that they want, as long as it's corresponding to the legal setting or the regulatory setting in a country. So it's not related at all to this complete response letter. The complete response letter on QM1114 was relating to manufacturing.
As you know, as you know it from Revance, to actually produce toxins is very, very difficult and complex. So it's not a total surprise that this happens. Other manufacturers have that issue.
How long do you think it's gonna take to solve that?
I don't wanna speculate on this. You know, the manufacturing is done by Galderma, so you would probably have to ask them.
Yeah, okay. But you're aware about the number of questions raised by the FDA in the CRL?
Because we are the marketing-
Of course. Yeah. Okay. But there is more difficult question to answer than others, so, yeah.
Yeah, I would revert you to Galderma to... Because they, they will have to work on this, because they are the manufacturer. Okay, with this, thank you very much, all of you, for joining, and have a good rest of the day. Bye-bye.
Thank you. This does conclude the conference for today. Thank you for participating, and you may now disconnect.