Ascendis Pharma (NASDAQ:ASND) reported second-quarter financial results on Thursday. The transcript from the company's second-quarter earnings call has been provided below.
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Summary
Ascendis Pharma reported total revenue of 339 million euro for Q2 2026, with product revenue of 315 million euro, more than doubling year over year.
Yorvipath revenue reached 252 million euro in Q2, achieving blockbuster status, while Skytrofa and Uviwell generated 55 million euro and 8 million euro, respectively.
The company anticipates achieving 5 billion euro in revenues by 2030, driven by existing products and the TransCon technology platform, with expectations to reach over 10 billion euro in the coming decades.
Key strategic initiatives include expanding the TransCon technology platform, pursuing label expansions, and advancing combination therapy trials, notably with Yorvipath and Uviwell.
Ascendis Pharma is addressing significant unmet medical needs with Yorvipath and Uviwell, both showing strong market uptake and patient satisfaction.
The company has ongoing legal challenges with BioMarin regarding Uviwell's IP, but management does not foresee a material impact on their growth trajectory.
Cash flow from operating activities is expected to exceed 500 million euro for the year, with strong financial positioning, including 812 million euro in cash and cash equivalents.
Full Transcript
OPERATOR
Ladies and gentlemen, thank you for standing by. Welcome to the second quarter 2026 Ascendis Pharma earnings conference. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you would need to press star 11 on your telephone. You would then hear an automated message advising your hand is raised. We ask that you please limit to one question and return to the queue for additional questions.
And to withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Chad Fugiere, Vice President of Investor Relations. Please go ahead.
Chad Fugiere, Vice President, Investor Relations
Thank you, operator, and thank you everyone for joining our second quarter 2026 financial results conference call. I'm Chad Fugiere, Vice President, Investor Relations at Ascendis Pharma. Joining me on the call today are Yen Mickelson, President and Chief Executive Officer; Scott Smith, Chief Financial Officer; Sherry Glass, Chief Business Officer; and Jay Wu, Executive Vice President and President, Ascendis US. Before we begin, I'd like to remind you that this conference call, including the Q and A session that follows our prepared remarks, will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. All statements made on this call, other than the statements of historical fact, are forward-looking statements. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of Skytrofa, Yorvipath and Ubwell, including label expansion and combination treatment; certain expectations regarding patient access and financial outcomes; our pipeline candidates and our expectation with respect to their continued progress and potential commercialization; our strategic plans, partnerships and investments; our goals regarding our clinical pipeline, including the timing of clinical results and trials; our ongoing and planned regulatory filings and our expectations regarding the timing and results of regulatory decisions; and our financial outlook and Vision 2030 objectives. These statements are based on information that is available to us as of today.
Actual results may differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see the Forward-Looking Statements section of today's press release and the Risk Factors section of our Annual Report on Form 20-F filed with the SEC on February 11, 2026.
In addition, during this call we will refer to certain non-IFRS financial measures. These measures are not prepared in accordance with IFRS accounting standards and should not be considered in isolation from or as a substitute for our IFRS results. A reconciliation of each non-IFRS measure to the most directly comparable IFRS measure, together with an explanation of why management believes these measures are useful to investors, is included in today's press release.
TransCon Growth Hormone, or TransCon hGH, is now approved in the US by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency, in addition to the treatment of pediatric growth hormone deficiency; in the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. TransCon PTH is approved in the US by the FDA for the treatment of hypoparathyroidism in adults, and the European Commission and the United Kingdom's Medicines and Healthcare Products Regulatory Agency have granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. TransCon CNP is approved in the US by the FDA to increase linear growth in pediatric patients 2 years of age and older with achondroplasia with open epiphyses. Continued approval for this indication, which was based on an improvement of annualized growth velocity, may be contingent upon verification and description of clinical benefit in confirmatory trials. Other than the approved products I've just described, our product candidates are investigational and not approved for commercial use.
The safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding product candidates shall be viewed as promotional. On the call today we'll discuss our second quarter 2026 financial results and we'll provide further business updates following some prepared remarks. We'll then open up the call for questions. With that, let me turn it over to Y.
Jan Mikkelsen, President and CEO
Thanks, Chad. Good day, everyone. During the second quarter, achievement of important milestones and strong demand for our TransCon products continue to drive the transformation of Ascendis Pharma into a leading global biopharma company. The uniqueness of the TransCon technology platform, our strong development and global commercialization capability, and our values and vision are the fundamentals driving this transformation. We believe the same strength will continue to drive Ascendis' growth in the following years, starting with the long-term durability of our highly differentiated, approved protein- and peptide-based combination products Skytrofa, Yorvipath, and Uviwell. We believe these products will be the key driver of our growth story for the next 10 to 15 years through global commercialization, potential for label expansion including combination treatments, and investment in patient support offerings. The continued expansion of the TransCon technology platform enables us to fulfill our plans to file at least one IND or similar yearly, each based on a new NCE, laying the foundation for strong growth for many decades.
This will also enable us to establish new therapeutic areas in addition to hypopara and growth disorders. As a further upside, our established partners are advancing TransCon candidates in large indications. This is why we believe Ascendis is well positioned for self-sustained long-term growth. Let us begin with a more detailed look at Yorvipath. Yorvipath is the first and only approved treatment for adults with hypopara that addresses the underlying disease by replacing the missing endogenous PTH throughout the body.
Uptake of Yorvipath has grown steadily since launch, both in the U.S. and many other countries, reflecting the significant unmet medical need among the more than 800,000 patients living with this serious rare disease in the geographic region covered by our global commercial infrastructure. Outside of the U.S., we see consistent new patient demand and continued expansion of global commercialization launches with full reimbursement. Yorvipath is now available commercially or through named patient programs in more than 35 countries.
This illustrates the strength of our ability to execute rapid, broad global launch of a rare disease product. In the U.S., new patient demand for Yorvipath in the second quarter has remained robust, consistent with prior quarters. In addition, precision prescribing is broadening and deepening. Patients who have successfully initiated Yorvipath treatment continue to stay on therapy, indicating a high level of satisfaction. We continue to be excited by the growth of Yorvipath in the U.S. and outside the U.S., and to see its continued strong performance. Data from our long-term Phase 2 and Phase 3 trials of Yorvipath presented in the second quarter highlight why Yorvipath is becoming a standard of care in post-surgical and all subsets of hypopara, including ultra-rare genetic causes like ADH1 and ADH2. Results showed sustained response rates of 82% to 86% for the multi-component endpoint with clinical benefit across multiple organ systems—CNS, kidney, small intestine, and bone—plus meaningful improvement in quality of life, with patient retention as high as 95% after five years of treatment.
Pretty unique. In parallel, we are working to further advance our leadership in hypopara with additional clinical trials that include expanding the label to include the age from 12 to 18 years and, in the U.S., higher doses for patients, and developing a once-weekly product for patients who are on stable doses of Yorvipath. Turning now to Uviwell, we believe Uviwell is positioned to become the market-leading therapy for achondroplasia. Rapid uptake of Uviwell is already transforming the U.S. market. Across the board, we see a highly favorable response among patients and physicians to Uviwell’s differentiated profile in the U.S. Through June, we had more than 170 unique patients enrolled. Since then, uptake has continued, with more than 220 enrollments and more than 65% approved for reimbursement in the U.S. through the end of July. Really a unique launch. The rapid uptake is by patients of all kinds of background—those switches returning to medical therapy or starting therapy for achondroplasia for the first time.
We believe Uviwell is really growing the U.S. market, which is exactly the pattern you would love to see when a highly differentiated product is introduced into areas where there still exists a high unmet medical need. Long-term data for the now completed pivotal approach trial show durable and consistent improvement in growth, leg bone, and body proportionality, along with a generally well-tolerated safety profile compared to placebo, underscoring that the community is quickly adopting Uviwell in the U.S. In the EU, a regulatory decision for Uviwell is expected in the fourth quarter of 2026. We are also making Uviwell available in select international markets through early access programs using the U.S. FDA approval. Longer term, we are pursuing expansion opportunities for TransCon CNP through ongoing and planned trials. These include ongoing activities such as infants 0 to less than 2 years of age—and we recently announced completion of this target enrollment faster than expected—adults with achondroplasia, children with hypochondroplasia, and we will continue with geographic expansions.
Turning now to combination therapy with TransCon CNP and TransCon growth hormone. The biological rationale for this combination treatment is clear and extremely well founded on science. TransCon CNP is removing the limitation caused by the overactive FGFR3 pathway, so TransCon growth hormone can provide a strong complementary effect. In addition, it has been observed that in achondroplasia there is a partial impairment of the IGF-1 growth hormone axis.
This is illustrated by children with achondroplasia having a negative IGF-1 SDS value, as shown in the demographics in both our Phase 2 and Phase 3 trials. In our COAST clinical trial for children with achondroplasia, this unique combination has demonstrated sustained transformative annualized growth velocity and height SDS, including improvement in body proportionality. Based on these results, we believe this unique combination of once-weekly TransCon-based therapies will transform the treatment of achondroplasia and other indications over time.
Our recent week 78 COAST data show sustained efficacy over 78 weeks with no compromises to safety and tolerability. This points to the potential for this novel combination to establish a new treatment standard in achondroplasia. The Phase 3 combination trials in children with achondroplasia will begin enrolling later this year. Turning to Skytrofa, the once-weekly growth hormone treatment builds on the mechanism of action of unmodified somatropin, with indications for pediatric and adult growth hormone deficiency.
We continue to be the number one long-acting growth hormone brand by value in the U.S. We are extremely proud that Skytrofa recently achieved more than 20,000 unique enrollments. This illustrates the strength of our capabilities—from supply chain, commercial infrastructure, and market support—to benefit such a large number of rare disease patients. And we are working to make TransCon growth hormone available to more patients through label and geographic expansions.
To support label expansion, including that described in our achondroplasia program, we are conducting the Phase 3 basket trial investigating TransCon growth hormone in ISS, SGA, and Turner syndrome as an integrated part of our global growth disorder strategy. We expect to launch TransCon growth hormone in the same countries where we also expect to launch TransCon CNP. Turning now to our partnership in metabolic disorders and obesity, our once-monthly TransCon semaglutide program with Novo Nordisk continues to advance.
In ophthalmology, our partner Oculis recently initiated a first-in-human clinical trial of an anti-VEGF treatment built on the TransCon technology in patients with wet AMD. In closing, by always putting patients first, Ascendis Pharma delivered three highly differentiated, leading TransCon-based products: Yorvipath, Uviwell, and Skytrofa. We are on track to achieve our Vision 2030 objective of being a leading global biopharma, building on a strong foundation for the future.
With that, I will turn the call over to Scott to review our financial results and some additional comments.
Scott Smith, Chief Financial Officer
Thanks so much, Jan, and good afternoon, everyone. I will touch on some key points surrounding our second quarter financial results. For further details, please refer to our Form 6-K filed today. Total product revenue was 315 million euro, more than doubling year over year. Total revenue for Q2 2026 was 339 million euro, which included non-product collaboration revenue of 24 million euro, which further included a 17 million euro milestone related to TransCon CNP.
Yorvipath revenue was 252 million euro in Q2, reflecting consistent new patient demand in the U.S. and continued growth outside of the U.S., reaching blockbuster status on a run-rate basis in the second year of launch in the U.S. Skytrofa contributed 55 million euro in Q2, which reflects increased demand in the U.S. and includes product sales to a collaboration partner. Uviwell was commercially launched in the U.S. during Q2 and generated 8 million euro in revenue in its first quarter on the market, reflecting strong demand and rapid conversion to paid therapy with limited stocking.
Turning to expenses, R&D expenses in Q2 were 76 million euro, up from 59 million euro in Q1, reflecting continued investment in our pipeline and innovation. Recall, Q1 included a favorable 11 million euro reversal of prior period write-downs of TransCon CNP prelaunch inventories. SG&A expenses were 173 million euro in Q2 compared to 145 million euro in Q1, reflecting additional investments in the commercial launches of Yorvipath and Uviwell to accelerate growth for the long term.
Operating profit of 220 million euro in Q2 included 158 million euro of other operating income related to the sale of the PRV. Non-IFRS operating profit was 92 million euro, and non-IFRS operating margin was 27%. Refer to our press release for details. For Q2 2026, net profit was 207 million euro, and non-IFRS net profit was 61 million euro. We ended Q2 2026 with 812 million euro in cash and cash equivalents, which includes the use of 56 million euro in Q2 for our previously announced share repurchase program, including the net settlement of certain RSUs following the settlement of our convertible notes.
We have no bank debt, no convertible debt, and 1.4 billion euro of equity. Turning to our outlook for the rest of 2026: for Yorvipath, we expect growth and performance consistent with prior quarters. For Skytrofa, we expect relatively stable revenue in the U.S. For Uviwell, we are encouraged by the early demand trends. We believe it is expanding the market and is on pace to be the leading achondroplasia therapy in the U.S., reflecting the large unmet medical need and the highly differentiated profile of Uviwell.
Our Q2 performance reinforces our belief that we can achieve 5 billion euro in revenues in 2030. With our existing portfolio and our TransCon technology as a strong foundation, we believe we are well positioned to grow revenue to more than 10 billion euro in the next decades while developing and launching new TransCon products with blockbuster potential. We expect significant operating leverage as revenue scales through the balance of the year, while maintaining new investments in global product launches and patient access to reach as many patients as possible and support our long-term revenue aspirations.
Even with these investments, we expect to generate more than 500 million euro in cash flow from operating activities this year. With that, operator, we are now ready to take questions.
OPERATOR
Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11. Again, we ask you to please limit to one question and return to the queue for additional questions. Our first question is going to come from Jessica Fye with J.P. Morgan. Your line's open.
Jessica Fye, Analyst at J.P. Morgan
Hey guys, good morning. Thanks for taking my question on that outlook for at least 500 million of operating cash flow this year. I think you gave that in the beginning of the year prior to the PRV sale, and I was just wondering if you're able to kind of update your cash flow expectations for the year. I know it's sort of like a greater than is unbounded, but curious if there's anything more you can add there? And then on that comment that UvWell seems to be expanding the market, is it possible to estimate how much of these patient enrollments are coming from market expansion?
Thank you.
Jan Mikkelsen, President and CEO
Thanks. Yes, for the questions and the other happy person besides me, Scott. Scott got the opportunity to be the first one answering questions. So please, Scott.
Scott Smith, Chief Financial Officer
Yeah. With respect to our cash flow guidance, just to be clear, greater than 500 million. I thought I heard you say 100. So, greater than 500 million. At this time we don't want to bound the upper side because we're initial into the launch of UvWell, and that's euro, by the way — 500 million euro, Jan likes to point out.
Jan Mikkelsen, President and CEO
Just related to that, and it comes back to what we somehow communicated last time we had this call, that we don't have really the insight into exactly the distribution of where the patients are coming from. Our general feeling, and how we see it, is that with such a strong demand, we have a really strong belief that it's not only coming from switches. It must also come from either patients that had stopped therapy or new patients that basically are coming to a situation — because of the highly differentiated nature of UvWell — that they want to start therapy.
And I think this is where we have this strong belief that we see an expansion of the market.
Jessica Fye, Analyst at J.P. Morgan
Thank you.
OPERATOR
Thank you. And the next question is going to come from Tazeen Ahmad with Bank of America. Your line's open.
Tazeen Ahmad, Analyst at Bank of America
Hey, good morning. Thanks for taking my question. So Jan, I wanted to get your thoughts about the IP challenge on UvWell. We know obviously what the blue-sky scenario is for Ascendis Pharma and, you know, most of the scenarios look positive. But can you just maybe walk us through what the potential outcomes are? This is for a patent that expires obviously in 2030. And so between now and then, can you just tell us what could happen and what the potential for, you know, payments that offenders would need to make in the worst-case scenario could be?
Jan Mikkelsen, President and CEO
Thanks, Cecile, for the question. And it's basically a question that is addressing the ongoing legal, I would call it, battle between Ascendis and BioMarin. Let me just come back to some facts. The fact is that this patent that we discuss got completely invalid in Europe, so we never really came to a discussion if we were infringing or anything like that. So when we see the situation outside the U.S., we got the patent invalid immediately through the patent system in Europe.
In the U.S., we never managed to come into the patent system because BioMarin selected to go to the ITC case, which is a system which, we can easily say, traditionally has not really dealt with a lot of cases dealing with branded pharmaceuticals. In the ITC case there will be a first opinion from a single judge, and he will come with an opinion here in August. And then the next time will be in December — there will be an opinion from the ITC — and then later on there will be a potential confirmation of the ITC decision two to three months after through a presidential order.
So you can see we are not getting any clarification in August in one way or the other. Even if it's positive for one company and negative for the other one, it's not really any kind of decision where it's going to be ending after the first initial opinion from a single judge, because the ITC case will be taken to a decision for — I cannot remember how many judges — that will be part of that decision. There is a huge opportunity to provide what we call public interest for this product.
And when we see the public interest — meaning the element of how these product opportunities are really serving an unmet medical need in the U.S. market with this rapid, rapid uptake — it's really, really clear there is a huge public interest to keep that. And just recall, I cannot remember one single case in the U.S. where a branded product that provides benefit to U.S. patients has been denied. You can see we're just in a case where it's only U.S.; it has been cleared ex-U.S. So whatever happens, it will not have any material impact on Ascendis' pathway. I can guarantee that. Some people take it up as life and death for Ascendis — this is totally not taken into perspective what it means for Ascendis — and out from that I see it's not really a material element for our destiny to be a leading biopharma and hit the 5 billion in 2030.
OPERATOR
Thank you. And our next question will come from Gavin Clark-Gartner with Evercore. Your line's open.
Gavin Clark-Gartner, Analyst at Evercore ISI
Hey guys, thanks for taking the question. Actually just wanted to ask on the earlier pipeline — you noted in your prepared remarks that the TransCon platform can fuel one IND for an NCE annually. I guess there hasn't been one yet this year. Should we expect one in the near term? And what exactly are the go-forward plans for the earlier pipeline? Thank you.
Jan Mikkelsen, President and CEO
It was because I somewhere felt that the two product opportunities that we have developed through our partnerships built on the TransCon technology would still be considered NCEs — the one that's now in clinic with Iconis, and the other one we expect to go into the clinic now with Novo Nordisk — still somewhere being developed through the TransCon technology funnel. And perhaps I shouldn't have done that, but I still believe I feel some kind of little bit ownership on these two product opportunities; at least we have major upside in both of them. So from that perspective, I still consider the potential this year two new chemical entities being entered into clinical trials. And I think Kenneth and his team and anyone else, they are working very hard on that — there'll be at least one of these new chemical entities coming into every year now. And I'm really proud about that. But it's also addressing the sustainability of Ascendis, independent of going out and buying something no one else wants to have.
And I think this is where we really feel extremely pleased by the situation — by being a fundamental company that's building on a strong, strong technology platform that provides both sustainability for ourselves but also a continued flow of potential partner licensing.
OPERATOR
Thank you. And the next question will come from Yaron Werber with TD Cowen. Your line's open.
Yaron Werber, Analyst at TD Cowen
Great, thanks so much. Question on UvWell. Do you expect that there is some seasonality in terms of new patient starts in the summer? Kids are going on vacation. We're getting a lot of questions on sort of the 60 patient start forms in April and now you're at 220. It sounds like there's 50 per month now. Is that sort of sustainable from now on? And then it sounds like you're planning — you think you could be the number one brand by the end of the year.
BioMarin, we think, has about 750 patients on drug. In the U.S., are you referring to getting to a higher number than that by, let's say, late February? Thank you.
Jan Mikkelsen, President and CEO
Thanks for the question. I actually don't think Ascendis Pharma has really made some clear forward-looking statement related to how we see UvWell accelerating and expanding the market in a quantitative manner. I don't think we have come with any kind of indication related to that. I have no doubt it will do it, but it's not the same thing that we're going to quantify it currently. I think after basically only four months in the market, I feel really not prepared to come with clear guidance to it before we have more quarters really into our analytical system where we basically can look at trends and other things like that.
But one person that really can give you good feedback — now we talk about the U.S. market — is Jay, and he's extremely enthusiastic about what he's seeing. He can give the latest view on what you see, how the market will develop. Thanks, Jan.
Jay Wu (Executive Vice President and President, Ascendis US)
As Jan mentioned before, four months in, we're not prepared to give longer-term guidance, but what we can say is we're incredibly encouraged by what we're seeing today. When you look at some of the fundamentals behind the UvWell uptake — whether it's prescriber reach, we talked a little bit before around this space, there are quite a few centers of excellence — we're seeing nearly 80% of them, already in a short four-month period, prescribe UvWell to their patients.
So even in early days we're seeing a lot of enthusiasm from providers around the clinical profile of this product. I think even more importantly, when you look at the patient enthusiasm, you can see in early days we're seeing a very positive trajectory. While we don't explicitly collect information on what therapy or non-therapy a patient is coming from — and again that's driven largely by the fact that we have a broad label, so we don't need that information in order to ensure that this patient can get on therapy; this is a rare disease — qualitatively we have heard confirmed anecdotes across all three categories for which our patients are coming from. And those three categories, again, are: one, patients that are switching from current therapy; two, patients that have previously discontinued pharmacological therapy and now want to return to pharmacological treatment; and then third, a group of patients that historically have sat out and have said, based on the clinical profile of UvWell, they now want to try a therapeutic option for the first time.
So all that, again, to underscore there is existing unmet need here, and because of our profile we're definitely seeing that patients are coming out of the woodwork from a growing-the-market standpoint, and we're just getting started.
Jan Mikkelsen, President and CEO
Just to summarize and to add on to Jay's excellent comments: Ultimately, I have no doubt we will be number one in the achondroplasia space. Ultimately, we will expand the market because of the unmet medical need, and that is just with the monotherapy. And when you look at how committed we are to this area, where we now are making a complete new standard with the compound treatment, I believe we are dedicated to be not number one in the first year but to continue to build for the next five to ten years with monotherapy, combination, integrated treatment regimens.
And I believe with our once-weekly TransCon product built on GOTOMO and CMP, we are extremely, extremely well positioned to be the leader in this segment.
OPERATOR
Thank you. And our next question will come from Derek Archila with Wells Fargo. Your line's open.
Derek Archila, Analyst at Wells Fargo
Hey, good morning, and thanks for taking the questions. Congrats on the progress. Scott, I just wanted you to clarify a comment on your revenue path growth for the rest of the year. I think you said it's going to be like prior quarters — I guess which quarters are you referring? Because I think the quarter-over-quarter growth in 1Q was negatively impacted; saw some catch-up here in the second quarter. So maybe you could just clarify which quarters you are referring to.
Scott Smith, Chief Financial Officer
Yeah, Derek, thanks for the question. I think that two points. One is the consistent performance with the KPIs that we've given you. For example, with enrollments, we expect those to continue and be consistent. The other would be, and you could refer to our prior quarters, and maybe Chad can point to prior comments. But I think that now that we've seen the full year, you know the various trends that will come into play related to Q3 and Q4 and then Q1 next year.
So we think actually folks did a pretty good job modeling out Q2, and now you have all the information you need to model the rest of the year going forward until we update basically the KPIs.
Jan Mikkelsen, President and CEO
Just to give you some kind of what is our value in this year? The value for us we want to give you, we want to give you not so you basically getting a lower number so we look like heroes. We want to give you the number so you are right nearly every time. And I think this is a way we try to come up with our different mathematic algorithm, how we see it, and give you all the information for you really to be right in this manner. And I think this is a way we like to be extremely transparent with everything we perform.
So we are quite sure that you basically can go out and really somewhere feeling always comfort with the guidance we give you. Great, thank you.
OPERATOR
Thank you. And our next question will come from Joseph Schwartz with Leerink Partners. Your line is open.
Joseph Schwartz, Analyst at Leerink Partners
Hi. Congrats on all the progress. Thanks for taking my question. As you embark on a phase 3 in hypochondroplasia, I wanted to ask how you're defining the enrolled population and how large do you see the diagnosed, treatable pool of hypochondroplasia patients who are not already being treated, in some cases if they're at the more severe end versus achondroplasia. Thank you.
Jan Mikkelsen, President and CEO
This is a very interesting question because it's actually in some way going into the situation on how we basically do genetic testing, taking a big patient group that in old days were called ISS, idiopathic — meaning we have no clue what is the underlying disease. And then you go out and do more and more and more genetic testing, and then when you find a mutation in the FGFR3 receptor and you find it in the right regions, then you suddenly are not an ISS patient, but then you are a hypochondroplasia patient, even if you don't have, you can say, the phenotype of looking like an achondroplasia patient or a hypochondroplasia patient that we saw 10 years ago. So therefore you can see the ISS population is in some way getting smaller and smaller, because genetic testing is basically going out and giving them an underlying reason why you are perceived to have a short stature without potentially having the other elements that you see for the phenotype of that. So this is where you can say when you go into ISS, you define it from a genetic perspective or you define it for a phenotype or anything like that.
And we are in a situation where, when you see the clinical trial how we are doing it, you will basically see that it's one of the pathways we have selected. Thank you.
OPERATOR
Thank you. And our next question will come from Daniel Bronder with UBS. Your line is open.
Daniel Bronder, Analyst at UBS
Hey team, congrats on the quarter. I'm on for Lee Watsack. We were just wondering if you could give us a little more color on the quality-of-life metrics in the COACH trial. You already alluded to the body segment ratios, but how should we think about benefit on arm span and other metrics?
Jan Mikkelsen, President and CEO
Just to recall, the COACH trial is the combination trial where we're combining the two TransCon-based products, our TransCon Growth and TransCon CNP. And I have to say, when I look at an element like arm span, we already reported some of the data. We have reported the 52-week data, and if you cannot find that deck I can send it to you, or Scott can send it, or Chad can send it, or I don't know — we have so many IR people I don't know their names more.
So from that perspective it already came out, and I have to say that was one of the, I will say, extremely positive surprises I saw, because when we looked at monotherapy, either a CNP-based one or a growth hormone-based one, we did not see the expected, hopeful development that we could hope for, but we definitely saw it when we looked at the combination therapy. And then you can ask me what is the scientific reason why you see a much more influenced benefit by the combination therapy?
And I have to say I don't know. But what we saw was an arm span that really gave us this hope. With the combination therapy you basically will be in a position that you basically could avoid all kinds of limb elongation surgeries in achondroplasia, both related to both legs and arms, by that. And it is slide number five, as I remember it. Scott, read off—
Scott Smith, Chief Financial Officer
The unprecedented improvements in the arm span with combination were plus 9.4 cm with the TransCon CNP-naive cohort and 7.9 cm with the TransCon CNP-treated cohort.
Jan Mikkelsen, President and CEO
So it was really compared to limb lengthening surgery. Exactly. Exactly. I have to say it was one of the days where I felt it was worth to go to a job and really can see the benefit of what we're doing. Okay, thank you.
OPERATOR
Thank you. And our next question will come from Yoonjong with Wedbush. Your line is open.
Yoonjong, Analyst at Wedbush
Hi, excuse me. Good morning. Thank you very much for taking the question. I wanted to confirm that you have not provided prescription number for Yorvipath in case I missed anything. And so I know that you said the patient demand remained robust in the quarter, so I wonder if there is any additional quantitative information that you can provide. And going forward, are you going to provide that number in the coming quarters? And I think you had this question before at the beginning of the launch — and when do you expect that you will feel comfortable providing a guidance in terms of the sales range on actual revenue?
Thank you very much.
Jan Mikkelsen, President and CEO
You are right. And I think it's starting to be a little bit appreciative every quarter coming out and saying that we have about more than 1,000 patients being unique enrolled per quarter. We have continued that measure, that we see steady state, steady state, and steady state. And we said last year that we will stop coming with this because it was too repetitive, and then because people doubted for the Q1, then we also came up with the Q1 and it was the same number again.
And what we're writing is that we see a robust, steady-state enrollment of unique new patients, and here we are referring to the U.S., with about 1,000 new patients every quarter. And we don't believe really — now we went over to Yorvipath, so now we're starting to give you a unique prescription enrollment of Yorvipath instead. So we always have one product opportunity where you will have something to play with with numbers and everything like that.
Scott, you have some comments for the last one?
Scott Smith, Chief Financial Officer
Yeah, I think our comments were directed to assume that the metrics that we've given you are consistent, because Jen wants to make our script shorter, so we don't want to repeat them more. And you should just assume that until we change it.
Yoonjong, Analyst at Wedbush
Great, thank you.
OPERATOR
Thank you. And the next question comes from Alex Thompson with Stifel. Your line is open.
Alex Thompson, Analyst at Stifel
Great. Thanks for taking the question, and I appreciate the color you provided to Tazeen's question around the ongoing legal battle with BioMarin. I guess as we think about potential scenarios here, and again acknowledging sort of this idea around the public interest of the product and unmet need, do you see a settlement as a reasonable scenario to think about, or is that really not something that you think is reasonable? Thank you,
Jan Mikkelsen, President and CEO
Alex, I think I'm a very flexible person, and one thing I really want to do — I will always do what is best for patients.
OPERATOR
Thank you. And the next question will come from Maxwell Skor with Morgan Stanley. Your line is open. Great.
Maxwell Skor, Analyst at Morgan Stanley
Thank you very much for taking my question. Just a quick one on Yorvipath durability. I was just wondering if dropouts are still mostly during the titration phase, and if you can comment at all on how reauthorizations are trending. Thanks.
Jan Mikkelsen, President and CEO
I think you're 100% correct. And when we see a patient being successful coming into a treatment with Yorvipath, coming over the titration part of it and being into the treatment after that, we see extremely, extremely low dropout. And I think that illustrates one thing — the patient satisfaction with this treatment. Because I'm now often being asked what can we do more for these patients in the therapeutic treatment of it. And when I see the satisfaction that it is in this way, then I feel that there is an extremely good persistence, retention, and everything, which really shows that we still develop once weekly for patients on stable doses, just to give patients the choice if they want to do it in this way. We will look at other ways to improve their life, like, for example, at-home capture, monitoring, and anything like that we can help the patient with, like it happens in type 1 diabetes and other things like that. So now you're addressing the element where we're saying we developed this here with a once-weekly profile. Even if we could make it — sorry, once-daily — because we wanted to do the titration most easily, because it's really complex to take patients off conventional therapy at the same time you increase the PTH in replacement therapy.
And that was why we made it as a once-daily — it's really to facilitate the best possible titration. But still we know it can be problematic for some patients, and Jay can try to explain what we are now doing to basically handhold the patient in this period so we also can make that extremely successful. So when you get a prescription, we know everything will be much more successful for the patient, not just after they're really being stable in the titration.
So Jay, will you explain the effort you're building in to really get that to be as soft as possible?
Jay Wu (Executive Vice President and President, Ascendis US)
Absolutely. Can chat a little bit more about certainly the investments that we're making, and also to answer your questions around drop-off and reauths. Yes. As we've shared before, the majority of the drop-offs is during that titration period, in terms of when patients experience the most amount of change and where additional education and a higher-touch support model makes sense. And then for reauths, that's actually pretty routine for us, so there really isn't much there in terms of it being a measurable effect on any kind of ongoing patient support.
We have patients reauthorizing throughout the year, and it's just part of our day-to-day operations. From an investment standpoint, we've invested heavily in patient-facing roles for which we've deemed our patient access liaisons. They support patients both pre-prescription as well as through the prescription process and post. So essentially we've seen a lot of success in early days with this field team being able to engage with this patient community.
They have appreciated this high level of support, and we of course support them throughout the journey to ensure that we're optimizing for patient experience. Great, thank you very much.
Jan Mikkelsen, President and CEO
One thing that I meant — now we focus on the U.S., but there is still a world outside the U.S. Outside the U.S., we have not seen the same level of dropout in this phase. It looks like the interaction is pretty well established between the physician and the patient and support system, really to see it without this kind of dropout. So it's basically a U.S. issue and day. So therefore we know we can get it to function. We just need to ensure that the support system also in the U.S. is strong enough to be sure that it's not a problem.
Maxwell Skor, Analyst at Morgan Stanley
Very helpful, thank you.
OPERATOR
Thank you. And our next question will come from Eric Joseph with Citi. Your line's open.
Eric Joseph, Analyst at J.P. Morgan
Hey, thanks for taking the questions. As far as your named access, your named patient programs or your early access programs, can you elaborate a little bit on which markets you're active in, whether eligibility might be determined by treatment status of a patient, and just generally how we should think about whether named patient programs could be meaningful contributors to patient volumes this year? Thanks. Yorvipath in particular.
Jan Mikkelsen, President and CEO
Okay, I just wanted to ask what product you were referring to.
Eric Joseph, Analyst at J.P. Morgan
Yorvipath.
Jan Mikkelsen, President and CEO
Yeah, I can guarantee that as we basically, in our prepared remarks, tried to put emphasis on, we have a global infrastructure in commercialization and patient support, product supply, and everything like that. Just the number of SKYTROFA rare disease patients we have taken over to the system: more than 20,000 patients. We are having the system functional in more than 35 different countries. So we are not a company that just needs to get started.
We already have established all this infrastructure, and what we're doing is that we're utilizing this established infrastructure that got established because of Yorvipath, because this is what we did with Yorvipath. We're using exactly the same infrastructure also for Yorvipath. So we will be where the patient is, and we will quite surely also serve the patient outside the U.S., and potentially the market is much larger outside the U.S. And I think we hope we also will see a large penetration in the U.S., where another short-acting product really failed to do it.
And we believe, because of the highly differentiated nature of Yorvipath, we will see a completely different pickup in the U.S. But definitely we have a strong, strong, strong focus on the ex-U.S., and we will give you some guidance when we come later in the year so you can also build up a model for the ex-U.S.
Eric Joseph, Analyst at J.P. Morgan
Excellent. Thanks for taking the question.
OPERATOR
Thank you. And the next question will come from Luca Issy with RBCM. Your line is open.
Cassie, Analyst at RBC Capital Markets
Great, thanks so much for taking our question. This is Cassie for Luca. So going back to Uvwell and Jay, the three categories that you very nicely touched on for the naïve, switch, and discontinued patients that are not on script: BioMarin mentioned on their second quarter call that less than 100 patients have switched off of Voxzogo. So the simple math that we're trying to do here is that it leaves you with about 70 patients in the second quarter who are naïve or returned to treatment.
So that's taking off the switch patients. Does that align with the numbers or impression that you have? And how does the dynamic look like between the truly naïve patients and the patients who were once on, stopped treatment, and are now returning to treatment? But to Uvwell and SKYTROFA very quickly, if you've commented or not on the ex-U.S. strategy for Uvwell, given the decision is pending and coming very soon this year. Thanks so much.
Jan Mikkelsen, President and CEO
I like your way of doing all the calculation and anything like that. I cannot support it or I cannot deny it, because I don't have the factual insight to, in some way, confirm any of the numbers. I also saw the number that came out, but I cannot really support it because I don't have the insight from our own numbers to really come out and come with any statement that indicates if I'm aligned or not aligned with it. Related to the ex-U.S., for me to understand, your question was this reflecting what is the limitation in the ex-U.S., or what was the question?
Cassie, Analyst at RBC Capital Markets
Thanks for asking. To clarify, more about are you committed to running the show by yourselves, or you're considering partnering? Given that 70% of the Voxzogo sales is historically coming from ex-U.S., it can be a quite heavy lifting.
Jan Mikkelsen, President and CEO
Yeah, but so basically in the ex-U.S. we have our direct market, which are, I think, 60, 70, 80, where we have our own commercial infrastructure and anything like that. It's pretty, pretty clear what we're doing there. Then we have our sales and distributions agreement, and this is, I think, it's 70 countries or something like that. Well, it's 80 countries that is covering this sales and distributions agreement, and then the vast majority of all of them are all three products.
So basically, there is already established infrastructure for the distribution. And then we have the two other models, where we have our partnerships: one in Japan, one in China, and it also has all the three products. So we don't need to go out and make any new agreements for anything. Everything is established, everything is running on full speed, and for some of the EU direct market we're just waiting for our expected approval here in Q4 this year.
OPERATOR
Thank you. And our last question is going to come from Faisal Kirsched with Jefferies. Your line is open.
Faisal Kirsched, Analyst at Jefferies
Hey guys, thank you for taking the question. Just wanted to ask a little bit on the Yorvipath lifecycle strategy. Can you give us an update on the latest on getting the higher dose into the label for FDA, and then also any update on weekly Yorvipath? Thank you.
Jan Mikkelsen, President and CEO
Yeah. What we see today is that we are enrolling the trial in the U.S., where we are evaluating the 30 to 60 dose range in two different means that has been aligned with the FDA in their design, what they wanted to see. And we see that enrollment going extremely fast. So we expect very, very, very fast, and you can say label expansion in the place where we don't have up to the 60. So we see that basically on just on execution.
Faisal Kirsched, Analyst at Jefferies
On weekly Yorvipath.
Jan Mikkelsen, President and CEO
Any update there? Yeah, I think there's no news in this way, that we're just executing and getting it into the market as fast as possible, out from the expectation that we see that not as any kind of LCM activity, but more patient support for patients that really are in the stable dosing, which are not a lot, after they have been in a situation where they have been stabilized with our daily treatment.
OPERATOR
Thank you. This is all the time that we have for questions today. This does conclude today's conference call, and thank you for participating. You may now disconnect.
Jan Mikkelsen, President and CEO
Thanks a lot, everyone.
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