Hello, and welcome to Ipsen's year-to-date sales conference call and webcast. The host for today is David Loew, Chief Executive of Ipsen. After a short presentation, there'll be the opportunity to ask questions, which you can do by pressing star one one on your keypad. With that, I will hand you over to David. Please go ahead.
Thank you, operator. Good afternoon or good morning, everyone. I'm delighted to welcome you to our year-to-date sales update. As you heard, I'm David Loew, Chief Executive Officer of Ipsen, and it's great to have the opportunity today to run through our performance in the first nine months of the year with you. Please note that this presentation is available on ipsen.com as we have just been signaled that there might be a small technical issue with the webcast. Please turn to slide two. This is our safe harbor statement, which outlines the routine risks and uncertainties contained within this presentation. Also, any commentary on growth you'll hear today will be based on constant exchange rates. Please turn to slide three. I will 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. The headlines today illustrate the strategic progress we are making. Sales in the first nine months of the year increased by 9.5% to EUR 2.2 billion, while in the third quarter, we delivered sales growth of 7.6% to EUR 775 million. I'm particularly delighted by the success of our growth platform, about which I'll talk more in a moment. Turning to the pipeline. While we look forward to stage three oncology data readouts before the end of the year for Cabometyx and Onivyde, we have noted the recent postponement of the FDA's advisory committee meeting on palovarotene in FOP. We made further progress this summer with our external innovation strategy, closing the agreement to acquire Epizyme in August, while signing a strategic partnership with Marengo Therapeutics to advance two IO candidates into the clinic.
Finally, we have today confirmed our guidance for the year with total sales growth anticipated to exceed 7% at constant exchange rates and the core operating margin above 36%. Please turn to slide five. As I mentioned a moment ago, sales in the first nine months of the year increased by 9.5%, while in the first quarter, we delivered sales growth of 7.6%. Looking specifically at our growth platforms of Dysport, Decapeptyl, Cabometyx, and Onivyde, they grew by 20.8% in the year-to-date and by 23.2% in the third quarter. Importantly, they continue to more than compensate for the decline in somatostatin sales. I'll now take you through the drivers of this performance. Please turn to slide six. We've delivered a strong Dysport performance this year across both therapeutics and aesthetics.
The market continues to be in robust growth, and the 24.8% increase in sales was in line with the performance last year. Our sales growth in the first half of 2022, particularly in aesthetics, was limited somewhat from the measures to further increase our manufacturing capacity. We began to see the benefit of that improvement in Q3 with an underlying strong market growth and a supply catch-up from the first half, resulting in sales growth of 43.3%. The increase in Decapeptyl sales in the year-to-date was mainly driven by continued volume growth across all countries while the recent relaxation of COVID lockdown rules in China boosted our performance in the third quarter. The growth in Cabometyx sales in the year-to-date was driven by the second line monotherapy setting in renal cell carcinoma.
The region in strongest growth was rest of the world, where sales were up by 74.2% as we continue to launch and gain reimbursement in more markets. Our overall Cabometyx performance has been supported this year by the growing contribution from the first line combination with nivolumab, including in France and Germany. The growth of Onivyde sales reflected a solid performance in the second line pancreatic indication in the United States, while there were increased sales to our ex-US partner. As you know, our guidance this year assumes an increased level of competitive activity for Somatuline. Sales of Somatuline declined by 2.8% in the year-to-date and by around 10% in the third quarter in line with this guidance. In North America, sales of Somatuline declined by 3.6% in the first nine months of the year.
I'm pleased that we grew our volumes and maintained overall market share. Pricing, however, has been adversely affected by the level of commercial rebates, and we have experienced unfavorable movements in channel mix driven by the increased effect of 340B. We have also been impacted by lower wholesaler inventories this year. In Europe, the impact from generic competition has increased. This has most keenly been felt in the third quarter in Germany, France, and Spain, and this trend in Europe is set to continue. Depending on the country, the impact has been on volume or pricing or a combination thereof, but we have seen solid volume growth in other markets this year, including in the U.K. and Italy. The Somatuline performance in the rest of the world has been excellent, with strong volumes and sales growth in a number of markets, including Japan and Brazil.
Please turn to slide eight. Turning to the major elements of our pipeline, this familiar chart is building quite nicely thanks to the progress of our external innovation strategy. Since we acquired Epizyme in August, we have added a number of trials across the three phases of clinical development. IPN60210, our oral SETD2 inhibitor, is in phase I development in relapsed refractory multiple myeloma and diffuse large B-cell lymphoma. While Tazverik in various combinations is in phase II and phase III development across a number of indications, including second-line follicular lymphoma. We have also had a number of near-term milestones for the pipeline, which I'll address on the next slide. Please turn to slide nine. There are two major milestones for the pipeline before the year ends.
We anticipate the phase III data readouts for Cabometyx in combination with atezolizumab in second-line non-small cell lung cancer, as well as the phase III data readouts for the Onivyde NALIRIFOX regimen in first-line pancreatic ductal adenocarcinoma. While an EMA decision on palovarotene for FOP is anticipated in the first half of next year, we note the recent postponement of the FDA's advisory committee meeting. Depending on the position of the FDA, a potential regulatory decision on palovarotene in the U.S. may occur in first half 2023. In addition to the phase II-B data readouts for mesdopetam in levodopa-induced dyskinesia, we expect to finish the first half of 2023 with a phase III data readout for elafibranor in second-line primary biliary cholangitis. Please turn to slide 10.
Based on our strong performance in the year to date, we have confirmed our full year guidance that was upgraded at our last set of results. We continue to anticipate total sales growth at constant exchange rates to exceed 7% this year. The core operating margin is expected to be greater than 36% of total sales, including the impact from the Epizyme integration. We expect a slightly more favorable impact from currencies of around 6 percentage points based on the average level of exchange rates in September. Meaning that we anticipate growing our top line by more than 13% in 2022. Please turn to slide 11. I'd like to conclude our presentation with four key takeaways. We've delivered another strong sales performance in the period with our growth platforms increasing double digits and more than compensating for the decline of Somatuline.
The size of our pipeline is growing nicely, and we have a number of near-term milestones, including several phase III data readouts. Our external innovation strategy is progressing well, illustrated by the recent Epizyme and Marengo transactions. While our financial guidance for 2022 has been confirmed today. Please turn to slide 12. Thanks for listening to our presentation. We now have time for your questions. Operator, over to you.
Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. Once again, star one one to ask a question. We will now go to our first question. Please stand by. Your question comes from the line of Elizabeth Walton from Credit Suisse. Please go ahead.
Hi. Good afternoon. Thank you for taking my questions. I have two topics. The first is palovarotene. Given the unexpected delay of the Advisory Committee that we were expecting on Monday, perhaps you could clarify what the additional clinical data is that the FDA has requested. Did any of your conversations with the agency ahead of the AdCom suggest that they required any additional data? Are these any different efficacy questions than those previously raised by the agency? Lastly, how long do you think it'll take to supply that information to the FDA? The second topic I wanted to touch on was Somatuline. We're seeing that Advanz is continuing to launch in new geographies without any apparent supply issues. We understand that Advanz is now taking a larger market share in Germany.
Can you clarify if there are any additional markets you expect Advanz to enter either in Q4 or into 2023? How we should think about the trajectory of European sales for Somatuline into 2023. In the U.S., if we look at the recent IQVIA data, we see Cipla continuing to gain market share. Can you help us think about how much of the decline we saw in the U.S. was due to Cipla's share taking versus the pricing pressures and the inventory changes you pointed towards? Thank you.
Thank you, Elizabeth. On your first question on palovarotene, as the discussions with the FDA are in fact still ongoing, we can't really elaborate at this moment on the additional data requests. We are gonna have another telephone conference with the FDA in the coming days. Was it anticipated? No, it was not anticipated, and it was also not previously raised. How long this is gonna take will depend really on the data request. What we have understood so far, we think we can respond relatively quickly, but I don't wanna run ahead of this because we still need to wait now for the next telephone conference that we're gonna have with FDA to understand better the impact.
On Somatuline, in terms of additional launches that you are gonna see in Q4, we can see that Italy is launching now Advanz. They have entered in two subregions, and this was anticipated. We will see gradual launches. We hear that they're also thinking about submitting in the U.K. and Sweden, for example. This is kind of what we have anticipated. On the trajectory for Europe, we will, of course, see continued gradual erosion, which is a mix of volume and price. Please remember, the rest of the world countries are developing very well, so it suggests the fact that they have not launched everywhere around the world, that in fact, there is still a certain supply constraint.
I would just wanna correct that perception because logically, they would have launched since a long time in many, many more markets. I think they're just ramping up gradually their production. In the U.S.., Cipla is gaining some market share. It's modest. You have seen also their estimation that they have communicated that they expect by quarter one next year to achieve about 10%. So far, they're around 4%. We are continuing to gain market share also on Somatuline. So we actually see volume growth for Somatuline in the US. However, the decrease in the sales that you have seen is stemming from more commercial rebates and also from the mix effect of 340B.
Thank you. We will now go to our next question. Please stand by. Your next question comes from the line of Richard Vosser, JPMorgan . Please go ahead. Your line is open.
Hi. Thanks for taking my question. A couple on Dysport please, and maybe one on Decapeptyl. On Dysport, just could you give us a little bit more color on the extent of the boost in Q3 that was related to the sort of the extra inventory going into the channel when the new manufacturing was started? And then also just an idea of the underlying demand. I think we had an idea of double digit underlying demand growth, I suppose, across both types of indications for Dysport. If you could give us an idea of that and whether you're seeing any impact on the aesthetic side of the business due to, you know, cost of living pressures, et cetera, at this point, and how we should think about that going into 2023.
I suppose just one more on Dysport. Just thinking about the supply into Russia, and how the proportion of sales that are Russian and how those are developing as well. Maybe I should probably stop there because that's three on Dysport. Thanks so much.
Richard, it is starting to become a long list of questions. On the extent of the boost from the inventory, it's relatively difficult to reconcile it very precisely because as you know, sales are going into therapeutics, which is growing very nicely, but also into aesthetics, which is also growing very nicely. Both markets are having a strong underlying growth. You talked about double-digit growth. You know, we are assuming about 28% in aesthetics, roughly 15% in therapeutics. To reconcile it's difficult because you don't have IQVIA data, for example, on aesthetics. A lot of sales are coming also from emerging markets where you have less details.
It's a little bit hard, but I think overall, I think we are in line now year-to-date with the 25% growth rate we had last year. I think we anticipate further growth in both markets. Now, of course, your first question, which is the cost of living, could it impact in 2023, for example, on the aesthetics market, which is probably the more likely one to impact if people have, you know, for example, less money in a recession. Too early to really, you know, speculate about this. We have seen that beauty market is very important for people. We see an expansion of younger and younger people, you know, getting these treatments, women and men. Clearly the market is having a strong underlying growth.
We don't anticipate that this is gonna come, you know, to a strong deceleration even in a recession. On the question that you were asking, we don't give sales split by country, as you know, but we see strong growth basically in all markets, in both in therapeutics and in Russia and in aesthetics, yeah.
Thanks very much.
Thank you. We will now go to our next question. One moment, please. Your next question comes to the line of Simon Baker, Redburn. Please go ahead.
Thank you for taking my questions. Two, if I may. Just firstly returning to palovarotene and the delay. I'm slightly confused here because on the one hand, if the FDA is asking for data a week before the event, that would suggest it's fairly peripheral. It's not a core issue that they're looking for and therefore should be relatively minor to fix. On the other hand, David, you said you were in discussions with the FDA. Is that reflective of not the size of the request, but the clarity of the request? I appreciate it's difficult for you to comment on this, but anything you could say to square that circle would be helpful. Secondly, a slightly broader question.
Now that another quarter has passed with Epizyme, I just wonder if you could give us an update on any potential changes to your expectations, be it for the commercial phase or pipeline assets within Epizyme, how that picture's evolved now that you have the close of the deal. Thanks so much.
Okay. Thank you, Simon, for your question. Yeah, of course, it's a bit unusual, you know, that the FDA postpones an advisory committee one week before, but you have seen that they did the same thing just yesterday and announced on Perrigo. I think we need to really see what they're gonna come back with. I don't wanna speculate further on this, you know, because these discussions are ongoing. We really have to wait and have the telephone conference with them. On your second question on Epizyme. It's very early days still on the integration. Remember that we closed the deal beginning of August. Of course, there was also the summer break.
On Tazverik, as you know, this drug has been launched, you know, more than a year ago. You know how it is when you take over a launch which perhaps has not been fully leveraged because, they didn't have all the resources that they needed to have. We have started to deploy our field force and our MSLs on the territory since the end of August. It's very early days. We have seen that many hematologists were not aware at all of Tazverik. There is, of course, quite a bit of work to be done in terms of relaunching, that drug and perhaps also making sure it's correctly positioned. On your second question on the pipeline, we are still assessing the pipeline. So far so good.
I think they have several preclinical compounds also being based on that platform, which are potentially interesting to us, and we are gonna communicate more, you know, towards probably the year-end results communication, because we wanna really go through it and really assess all the science around it.
Great. Thank you very much.
Thank you. We will now take our next question. Please stand by. Your next question comes from the line of Michael Leuchten from UBS. Please go ahead. Your line is open.
Thank you very much. Two questions, please. Just going back to palovarotene last time, this did spill over into Europe as well and sort of triggered a delay because the ABCs obviously talk to each other. Is there anything you can say on that for now? I presume not, but I thought I'd ask. Just going back to Dysport, if it's hard to really grasp what's in the inventories and what isn't, how did the first half present itself, where you said you weren't quite able to deliver to the demand? Were customers actually not able to get product even though they ordered it?
Is there just a sort of an assessment that the market was growing a little bit quicker than the stockout that you had or the products that you had shipped from your facilities? Thank you.
On your first question. Thank you, Michael. On palovarotene and is there a potential impact on Europe? We have not had any further questions from Europe. You know, so far Europe doesn't seem to be changed. We expect the CHMP opinion in December, so that has not changed. On Dysport, to try to reconcile the sales, what we have seen is that when you take the underlying market growth and you have seen our sales performance in Q1 and Q2, which were with a growth of roughly 15%, you can in fact say that we were not able to deliver to all the customers the quantities that they would have liked to have. Of course, there was a bit of a depletion of inventories in the distribution pipeline.
You know, there is of course then, part of this effect kicking in in Q3. But you also need to remember that the market itself is growing. You know, any inventory needs that the distribution channel is gonna have is actually, while the market is growing, also gonna increase because they keep days on hand, depending on the sales trend. They are gonna, you know, increase also the days on hand that they wanna keep because they know that the sales are growing because the market is growing very nicely.
That's why, you know, when you look on a year-by-year, last year growing 25%, this year growing 25%, we can say that probably a piece of this first half was indeed that we could not fully satisfy the demand in the market, and they had to eat into their stock. There were very few places with very short stock-out periods. You know, the major markets we were generally able to deliver. It's more a kind of an inventory effect.
Thank you.
Thank you. We will now go to our next question. Please stand by. Your next question comes from the line of Richard Parkes from BNP Paribas. Please go ahead, your line is open.
Hi. Thanks for taking my questions. I've got a couple. Firstly, just looking out to 2023 and the pushes and pulls on margin. I think if you look at consensus forecasts, it looks like analysts are modeling a 250 basis point core margin contraction in 2023, but only an incremental EUR 150 million in OpEx, which seems a little bit light to me given full year of Epizyme, likely increased marketing support and expected increases in R&D behind palovarotene and elafibranor, as well as overall inflationary pressures. I know you're not gonna guide, but if you could give us some kind of sense of the moving parts there and thoughts on consensus, it would be helpful. Maybe there's some offsets from cost savings that I'm missing.
The second question is just a very simple one on Somatuline. It's gone from declining in high single digits year-on-year in Europe in the second quarter to 20% year-on-year declines in Q3. Is that kind of trajectory we should expect and for US Somatuline heading into the fourth quarter and maybe Q1 next year? Or is there reason to be more optimistic those sales can be defended? Thank you.
Perhaps on your first question I ask Aymeric to answer.
Yeah. Regarding the guidance for next year, as you said, we will provide that next year. I think at the previous call, we framed how we see 2023, and I think that clearly our performance in Q3 is confirming what we see, which will mean that we should be able to continue to grow our top line, despite the gradual erosion that will continue for Somatuline. I think there will be further dilution from the Epizyme acquisition, as you mentioned. We know that there will be pressure also from the global environment on costs related to inflation. We are clearly committed to mitigate as much as we can, with efficiency, the impact of the mix on the gross margin and also those additional costs.
That's why we are confident that we should be able to manage the decrease of the operating margin as we have guided with acquisition of Epizyme under Q2 calls.
On your second question on Somatuline regarding the U.S. In the U.S., as we have said, we anticipate a continued gradual erosion. It's a 505(b)(2), so it's not the same as Avastin with a generic. We have also two different J-codes in the U.S. It's not at all the same situation. Just perhaps to keep in mind, in Q4 last year, that was a relatively strong Q because there is always a bit of inventory buildup, which might not happen, of course, this year, since the inventory levels have adjusted given the appearance of 505(b)(2). Just that to keep in mind.
You might see perhaps a little bit of stronger erosion than what we usually would anticipate, but that's gonna smoothen out again in 2023. This is just an effect that we need to keep in mind. On 2023, we're not giving guidance right now, but as we said, this is a gradual erosion. We have not seen you know massive penetration of Kuvula here. But of course, there is you know a bit of pricing pressure, as I mentioned, due to commercial pricing, but also because of the mix effect of 340B, which is an interesting phenomenon, but which is impacting Somatuline.
Thank you.
Thank you. We'll now go to our next question. Please stand by. Your next question comes to the line of Charles Pitman from Barclays. Please go ahead, your line is open.
Hi. Thank you for taking my questions. Two, please. Maybe just another one on Palovarotene to dig into it. I accept that you have some more discussions to come with the FDA. In terms of how we think about it, given the outcome now of the rearranging and the 60-day notice period that's required, should we be thinking like a six-month delay is sensible at this point? And then just secondly, on Decapeptyl. Could you provide any more color on the impact of the Nigeria shipping? Is this just brought forward from 4Q and expecting that out by the end of the year? And then maybe just on the good growth in China, could you give us some idea of the growth dynamics there? Thanks.
On your first question, you know, I mean, I really don't wanna speculate on this because we need to really wait for the discussion with the FDA. You know, if they wanna stay in the same procedure, they could have a maximum review extension of three months, not six months. We need to really wait, you know, that's the current regulation of FDA. We need to really wait to hear more for them to then provide you more precise guidance. On Tecentriq, Algeria, you know, we don't provide these kind of details because, I mean, we don't go into brand per country. On shipments.
What we can say is that on China, that you have heard in my script, we have seen the easing of the COVID measures, and so that market has accelerated in terms of growth again. We are benefiting from that, and seeing good growth now again in China. But we need to be seen, right, in China. I mean, you have seen the Communist Party meeting, et cetera. We have to see how China develops. What we are seeing right now is that if there are lockdowns, they have not so far locked down whole cities, but only sometimes called in individuals or very small parts of cities. That's just the current situation that we have in China.
Brilliant. Thanks.
Thank you. We'll now go to our next question. Please stand by. Your next question comes to the line of Keyur Parekh from Goldman Sachs. Please go ahead. Your line is open.
Hi, and thank you very much. Three questions if I may please. The first one going back to palovarotene. If I understand correctly, you're assuming a regulatory decision in the U.S. for palovarotene in the first half of 2023. Just wondering kind of what gives you the confidence that the FDA is going to be in a position to review the additional data that you provide and potentially host an advisory committee over the next kind of six, seven months or so. Just kind of the thought process behind that first half 2023 kind of timeline would be very helpful. Secondly, as we look at your early-stage pipeline on the longer-acting neurotoxins, when are you expecting the phase I data to be presented?
Can you help us understand why kind of IPN59011 is not being considered for therapeutic use at this point? Lastly, as I think about Somatuline into kind of 2023, how sustainable is the rest of the world growth that you have delivered in 2022 so far? Thank you very much.
Thank you, Keyur, for your questions. On your first question, you remember, of course, our slide two that, you know, these are forward-looking statements. There are, of course, risks and uncertainties attached to this. I just want to repeat that because the discussions with FDA are still ongoing. Our confidence level so far is at our, I would say, best estimation. But you know, we need to really have now the discussions with the FDA to understand better, okay, what exactly is the new data that they wanna have so that we can really assess the scope and, if you know, that hypothesis that we have given to you is in fact gonna be confirmed.
On the LANT, it is a phase 1/2 trial, so we are in the follow-up phase right now. We should have results which is gonna inform our phase III trial by the end of 2023 for aesthetics. We have two candidates. We have the AD and the A. The AD is really our lead compound. The A was a backup compound because the AD is the newly engineered recombinant one. We have had in fact higher hopes on this candidate. We wanted to have also a little bit more, let's say, traditional one with the candidate A. It turns out, in fact, that our hypothesis was correct, that the AD seems to be more differentiated, and that's the one we're gonna take forward.
Of course, we have seen mouse data, which has shown that the LANT has in fact a potential to be higher dosed and has much, much less spread into surrounding tissue, which is a key point when you wanna have a truly long-acting neurotoxin. We have seen this in preclinical models, and it seems to confirm now also in the phase I data that we are seeing that we have actually been able to dose LANT much higher than what we have initially thought. That has taken a little bit more time to develop, because we had to have the dose escalation. This has actually been a good thing.
We are now in the follow-up phase, and we should be able to have data by the end of next year, which is gonna inform a potential step into the phase III. In terms of your third question on Somatuline 2023, again, we're not giving guidance on 2023. What we can say is that the rest of world markets still have significant potential because neuroendocrine tumors have not been treated as they should be treated, and these markets are still growing quite significantly. It of course then depends if one day could also start to launch in rest of world markets. So far, we see relatively little activity outside of the key market.
We hear that they're gonna launch in Australia, but you know, there are many more markets around the world and so far we have not detected activities there.
Thank you. We will now go to our next question. One moment, please. Your next question comes from the line of Elizabeth Walton from Credit Suisse. Please go ahead.
Thank you so much for taking my follow-up. I have another question on palovarotene. You mentioned the Perrigo AdCom that was also delayed this week, but that company also got a notification that their PDUFA was also pushed by three months. Can I check that your working assumption is that there will be an AdCom prior to a regulatory decision by the FDA? If you have any opinion as to why a new potential PDUFA date has not been communicated to you yet? Thank you.
Okay. I think that's gonna be our last question. Thank you, Elizabeth. On the advisory committee, you know, they have not communicated on cancellation. They have communicated on postponement. We have to just, you know, take it as what it is. I mean, this is the communication from the FDA. We, since they communicate on a postponement, we assume that we're gonna have an advisory committee. The new PDUFA date has not been communicated. As you have seen on the website, they don't express anything on the PDUFA date.
Again, here, we just need to wait for FDA coming back with more precision on the exact new data that they would like us to analyze, and then on any potential further changes to the current process, which as I said, you have seen it on the website, has so far not been communicated to the public nor to us. With this, I hand back to the operator for concluding our call. Thank you very much for your attendance.
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by.