Ladies and gentlemen, thank you for standing by. Welcome to Ascendis Pharma APPROACH Trial Top Line Results. 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 will need press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. In the interest of time, we do kindly ask to limit to one question and one follow-up. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Tim Lee, Senior Director, Investor Relations, Ascendis Pharma. Please go ahead.
Thank you, operator, and thank you everyone for joining our conference call this morning. I'm Tim Lee, Senior Director of Investor Relations for Ascendis Pharma. Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer, Scott Smith, Executive Vice President and Chief Financial Officer, and Dr. Aimee Shu, Senior Vice President and Chief Medical Officer, Endocrine and Medical Sciences. Before we begin, I'd like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statement may include, but are not limited to, statements regarding our expected timing for submission of certain regulatory filings related to TransCon CNP.
Our expectations regarding TransCon CNP's potential to meet the needs for a treatment addressing the health and quality of life complications of achondroplasia, our development plans for TransCon CNP, our ability to apply our TransCon technology platform to build a leading, fully integrated biopharma company, particularly in the treatment of skeletal dysplasia and growth disorders, on our plans and objectives for future operations and commercialization activities. These statements are based on information that is available to us today. Actual results and events could 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 our forward-looking statements section in today's press release, and the risk factors sections of our most recent annual report on Form 20-F, filed February seventh, 2024. On the call today, we'll discuss the TransCon CNP APPROACH trial top-line results. As part of today's webcast, we have an accompanying slide deck that you can find on the investor relations section of our company website. Following some prepared remarks, we'll then open up the call for questions. And with that, let me turn it over to Jan.
Thank you, Tim. I'm really proud, happy to be here today, and I will be sharing the presentation that I hope you have found online with Aimee Shu, our Chief Medical Officer. I will take the easy part because I will only take the first slide, number three. Reminding you, in APPROACH trial, we enrolled children between two and 11 years because we wanted to be quite sure we, from the beginning, could get the broadest treatment option for the patient. We know it's important to initiate treatment extremely early. When we take this entire patient population between two and 11, we have a treatment difference on 1.4 cm per year at week 52.
When we go to a more narrow group, the patients between four and eleven, because that is basically the only way where you can compare the population treatment effect to already approved therapy. We actually have a treatment difference when we incorporate taking into account the baseline before the treatment, trying to compare apples to apples in the best possible way when you compare inter trials. That is the best way we can do it. We come to a treatment effect of 1.78 cm per year. We can support all our growth data with both when we look on the growth, on Z-score, other elements that Aimee will go through it. We feel really, really proud. We feel proud about how we can go out and really also improve the treatment related to comorbidities.
As we always have said, we are going for a treatment, and when we see all the data we have, we are still analyzing the data related to this element. We still getting data coming in, all of them showing the same trend. We also addressing comorbidities. In any treatment, safety and tolerability are, is a key issue. When it come to pediatric, it's a must. You cannot compromise there. We saw a safety profile, safety results that really, in my view, is one of the most favorable safety profile I have seen. Key effect I would like to take up before Aimee Shu go to all the entire integrated safety effect, is that we not saw any effect of hypotension. Remember you, we didn't have any kind of prior administration of oral before they took TransCon CNP, anything like drinking one-third of a liter of water or other effect.
The other part, we someway are correlating back to. It's back to the science, because we basically defined TransCon CNP to provide a continuous exposure on CNP. And from that perspective, we will not actually ever have expected to see any effect on hypotension. Because of the TransCon technology, which are a product technology, we basically are injecting an inert drug. That is also reflected in the injection site reaction. What we see, it was well tolerated with extremely low frequency of injection sites. So to sum it up, once weekly TransCon CNP has the potential to address the needs for an efficient, safe, tolerable, and convincing treatment. I will now move it over to Aimee Sh u, where we go to all the data, and I will be back on the last slide.
Thank you, Jan. I will start on slide four, which is the trial design for the pivotal APPROACH trial. So to summarize here, we sought to enroll approximately 84 children, and that's what we did, ages two to 11, with achondroplasia, and they were randomized in a two-to-one fashion to TransCon CNP, also known as navepegritide, or placebo. The primary analysis was conducted at week 52, so these are the results we are talking about today, and we are just at the top line. Primary endpoint was Annualized Growth Velocity, AGV, at week 52, so at a point in time.
Secondary endpoints included change from baseline in height Z-score, also known as height SDS score, at week 52, which normalizes growth by sex and age, and also some measures of quality of life, including the Short Form-10 Physical Summary at week 52, and certain measures of the Achondroplasia Child Experience Measures, ACEM for short. We did have safety endpoints, of course, including treatment-emergent adverse events, and injection site reactions and blood pressure, and other selected endpoints, including radiology and upper to lower body segment ratio. I will turn to the next slide and walk you through two slides about baseline demographics and characteristics. On this slide, we show that the average child enrolled was 5.7 years old, and that 57 children were randomized to TransCon CNP and 27 to placebo.
There was a good split between girls and boys, and as we randomized by strata, that turned out to be nicely balanced as well, so the randomization strata were ages younger than five, ages greater than five, five or older and female, five or older and male, and this was done based on what we knew from the literature and how growth rates seem to happen in achondroplasia. We also recruited from around the world. On slide six, I continue baseline demographics and characteristics, and here you can see the mean height was 88 cm, with an achondroplasia-specific height Z-score compared to the CLARITY Database, close to zero, so here we're showing 0.09, showing that this population, in terms of their height and growth up till now, is characteristic of the general population with achondroplasia at large.
Compared to the general population of average stature children, as measured by the CDC or Centers for Disease Control growth curves, these children were minus five standard deviations or had a Z-score of minus five below average, so very short compared to the average stature population here. In terms of the genetic variance causing achondroplasia, again, very representative, with the most common known genetic variants being also the ones reported here and some other less common ones as well. Diagnosis generally occurred close to birth, so as you can see, between the two treatment arms, they were well-balanced at key baseline demographics such as height, sex, and age, and now we'll turn to the safety part. Here with treatment-emergent adverse events, you see that most of the adverse events were mild and moderate. That's grade one and two.
There were some that were reported as treatment-related in that, the next row. We did have some serious adverse events. All were reported to be not related to study drug. Serious adverse events, as you know, is a regulatory term that requires hospitalization or surgery. We had adverse events of special interest. This is another regulatory term asked by the regulators based on data they know from medical therapies for achondroplasia that are of particular interest to them. These included injection site reactions, which accounted for all of the adverse events of special interest here, fractures and symptomatic hypotension, symptomatic low blood pressure. As you can see, the rates of injection site reactions were similar between the two arms, 19% and 15%. This is quite low in general for a treatment that requires weekly injections.
Also, there were no adverse events that led to discontinuation of study drug or withdrawal from the trial. So as you can see here, the safety and tolerability results for TransCon CNP were comparable to placebo, and the eight adverse events were generally mild. On the next slide, slide eight, we summarize a lot of what I just explained in the prior slide. I want to focus specifically on the last two bullets on this slide. Because TransCon CNP acts on a natriuretic receptor, of course, blood pressure is of interest. But it was measured carefully at all study visits, and symptoms and signs that could be associated with low blood pressure were also carefully assessed during this trial. I'm really happy and pleased to report that there was no evidence of a hypotensive effect across the trial.
No blood, no low blood pressures that were asymptomatic, nor a signal for increase of low blood pressure that was symptomatic. In terms of injection site reactions, they were generally mild. They were all mild. All of them were grade one, and we had a relatively low frequency. In this case, 0.41 events per patient year. And now I will turn to the efficacy portion. This starts on slide nine. For the trial's primary endpoint, annualized growth velocity at week 52, what you see here is the adjusted mean annualized growth velocity, or the modeled AGV, is 5.89 cm per year. So these children allocated to TransCon CNP were growing at 5.89 cm per year, compared to placebo, who were growing at 4.41 cm per year.
The estimated treatment benefit is 1.49 cm in favor of TransCon CNP, with a confidence interval that excludes zero and a highly statistically significant P value. So I'm happy to report that TransCon CNP and this trial achieved its primary objective, demonstrating increased growth over placebo. On the next slide, we have a figure. This is slide ten, showing observed AGV over fifty-two weeks. And what we like about this slide and this figure is that, as you can see, compared to AGV at baseline, there was an early trend for better growth apparent at week twelve, and this was consistent throughout the year.
Such that the kids allocated to TransCon CNP were growing at 5.95 cm, unadjusted, at the end of the trial, compared to three point nine five at the beginning, giving them an increase in AGV of 2 cm per year. And now on slide eleven, we show subgroup analysis for these, for this primary endpoint. So these subgroup analyses are split out by age. So we have ages two to four years old in the left-hand column and five to eleven years old in the right-hand column. And as you can see here, there's a treatment benefit in favor of nabipagratide in both age groups, with the age group of five and older reaching an impressive 1.78 cm per year in treatment benefit. So one point seven eight years higher, at 1.78 cm per year higher.
These were both statistically significant. Turning to slide 12, we present another way to look at growth, and the results are very similar. In this case, we're looking at change from baseline in AGV by age group. We're looking at week 52 minus the growth rate at week 0 and showing the difference. What you can see here is, once again, there's a treatment benefit in favor of TransCon CNP across both age groups, the younger than five and the older than five. Again, here it's 1.78 cm per year in favor of TransCon CNP, even by age group. This is, you're correct, the same 1.75, even though derived from different means, 1.78 cm per year.
This, to me, shows that the data are quite robust with these, this larger data set that we have recruited. Any way you look at growth, it is quite good. On slide 13, we turn to a secondary endpoint, and this one was changed from baseline in height Z-score at week fifty-two. On the left-hand panel, we calculate the Z-scores compared to a normative reference range for children with achondroplasia untreated with medical therapy. This is the Clarity database. On the right-hand panel, we show the children compared to children of average stature using the CDC database, which is traditionally used in measuring growth for children across the world. What you can see is, I'll go back to the left panel, that the children grew well and increased their growth percentiles and jumped to a higher growth curve either way you looked at it.
The children treated with TransCon CNP increased their height Z-score or Z-score by 0.3 of a Z-score, 0.3 of a standard deviation, and compared to placebo, that was a 0.28 Z-score treatment benefit. Even more striking, on the height Z-score compared to the general population, we saw the same thing, a 0.3 Z-score improvement for TransCon CNP. We have figures showing this in the next slide, that's slide 14, illustrated here. Again, on the left panel, compared to the achondroplasia height Z-score, and the right panel compared to the general population, the CDC height Z-score. I'd like to walk you through what these curves mean. On the left-hand side, with TransCon CNP shown in the gold line, these children are growing better than expected, better than natural history, as you would expect, given that they are receiving TransCon CNP.
Whereas those randomized to placebo grew at natural history. In other words, they were growing at the same Z-score that they had come in on, the same growth curve as generally children would stay on without therapy. On the right-hand side, we do a comparison to children of average stature. What you can see here is, as expected, the children are losing ground. The children randomized to placebo are losing ground, right? They're with each passing quarter, and in this case, with the passing year, they are going to a lower growth curve, and they are losing in terms of height compared to the average stature, relative to the average stature children. What we're really excited to see here is that the children randomized to TransCon CNP actually did better than that.
Not only did they hold their ground, but they were able to cut up higher onto a higher growth curve during this year, suggesting that they had gotten some catch-up growth in this past year with TransCon CNP. Now I'll turn to results beyond linear growth. As mentioned before, we looked at several measures of quality of life, and in the total trial population, we're happy to see that treatment with TransCon CNP resulted in numerical improvements in health-related quality of life compared to placebo, as observed in several ACEM domains. In general, at baseline, we had some differences reported by the parents of children in this trial compared with our phase II trial.
We're happy to say that as we looked at the selected endpoints here beyond linear growth, we did see some health-related signs and symptoms and quality of life improvements across the ACEM observable signs measures, physical functioning, daily living, and emotional well-being. We did not see any trend in the SF-10. We also will show in the next slide some exploratory endpoints, including muscle function testing. I'll show you on the next slide, these forest plots. That's on slide 16. The left panel shows when we looked at the overall full analysis set, intention to treat population, and then the right panel looks at when we restricted the analysis set to those patients who were reporting quality of life burden greater than 20 points at baseline.
These are for the ACEM measures, and I will let you know that the ACEM measures are scaled from zero to one hundred, with one hundred being the highest burden and zero being no burden. When we looked at the full analysis set, what you can see here is the point estimate was generally favoring TransCon CNP across these domain subdomains, where the blue dots are all in the blue zone and giving a negative number, meaning that the score got lower during the trial. We did have many patients who were reporting a zero score at baseline, and so as a subgroup analysis, we decided to look at those who were reporting burden greater than twenty points at baseline. When we did that, what you see is on the right-hand panel, the estimates, the point estimates got even a little bit better, more negative.
With the first one, ACEM observable sign and measure, even coming to the border of clinical significance with the confidence interval at zero. These ACEM, these four measures here were selected because of interest based on our phase II trial and because of being more compelling, we thought, to regulatory authorities. We also understood and understand that children younger than five years old have the greatest gap in achieving developmental milestones and in physical functioning compared to the average stature population. So when we looked at this predefined subgroup analysis for ACEM physical functioning, younger than five years old, we found this trend, and it was also statistically significant, that the point estimate also favored treatment with TransCon CNP with a p-value of zero point zero three seven.
This was a predefined analysis and encouraged us to look preliminarily at our muscle function testing of the youngest group that we tested. We tested starting at five years old, at week 52, and interestingly, here we see also represented in the blue shaded area, that these children had stronger muscle. In this case, this was a knee extensor test, so how, how much could they kick? How much, with how much force could they kick? So we are very encouraged by these quality-of-life measures, showing that TransCon CNP may have benefits beyond linear growth. Now, on slide 18, we show the upper to lower body segment ratio and how this changed over time up through week 52. On the left-hand panel, you see the children randomized to TransCon CNP, on the right-hand panel to placebo.
What you see here is even with the robust growth, that the children were maintaining, body proportionality with an improved upper to lower body segment ratio that was statistically significant compared to their baseline, whereas the placebo was unchanged from baseline. And now slide 19 for what's next in our clinical program. We're really happy to see that the pivotal APPROACH trial results support the desired target product profile of once-weekly TransCon CNP, delivering continuous exposure of CNP. What we mean by that is that, as you know, TransCon CNP was delivered, is delivered once a week with a nice PK profile that avoids any Cmax of CNP and thus should not cause hypotensive issues. And that is indeed what we saw.
I'd like to remind you that in our clinical program, because we did not expect any hypotension, we did not have any recommendations in the protocol to train caregivers or physicians to look out for signs and symptoms of hypotension necessarily, or to have recommendations to drink and eat plenty before receiving injections, and even with this, they did very well with their blood pressure. We plan to submit the New Drug Application to the U.S. FDA for the treatment of children with achondroplasia next year, first quarter, and to the EU or the European Medicines Agency, a Marketing Authorization Application in the third quarter of twenty twenty-five. Our comprehensive development plans for TransCon CNP continue with ongoing and planned trials to support additional patient populations.
And I'm happy to say that all 82 children who completed this APPROACH trial elected to roll over from the double-blind period into the open-label extension and are still continuing to this day. So with these wonderful results and knowing with once weekly Skytrofa and with the wonderful results today from TransCon CNP, Ascendis feels uniquely positioned to become the leader in the treatment of skeletal dysplasias and growth disorders. And with that, I will pass the microphone back to Jan.
Thank you so much, Aimee. I would like to go to slide 20, our Vision 2030 . I would only focus on one-third of the focus, the top one, being the leading endocrinology rare disease company. The first bullet, achieve blockbuster status for TransCon PTH, TransCon Growth Hormone, and TransCon CNP to worldwide commercialization. Our first product, TransCon Growth Hormone Skytrofa, is now approved in Europe and U.S. and other market. It launched in Europe, launched in the U.S. Even with the recent, what I call reset in Skytrofa, we have really seen the pathway, how we building Skytrofa in the U.S. alone up to a blockbuster product by continue changing our commercial strategies, because we will never compromise the value we have in Skytrofa because of its best-in-class nature. We will continue to do label expansion so we can achieve that status.
Today, we have approval of TransCon PTH, Yorvipath in Europe and U.S., and other markets. We have been launching Yorvipath in Austria, Germany and are for full launch. We have patients in many, many other countries. We're looking forward to launching Yorvipath in the U.S. here in the first quarter. We feel confident that this huge unmet medical need will really have a patient-focused treatment with Yorvipath.
With this data, we have achieved the TransCon CNP. Also be presented with Aimee. I feel confident we have the same pathway with CNP. And I'm feeling proud of Ascendis. I'm feeling proud about our algorithm for product innovation, our TransCon technology, that really have facilitate. We could take three preclinical candidates and really develop them so far, and I believe we will also get all three approved. We have the fundamentals with these three product really to be the leader in growth disorder.
We have our once-weekly Skytrofa TransCon growth hormone, our once-weekly CNP. And we really would develop then in the twenty-plus growth disorder, really to building up the leading position as the only company that has both entity. We will be in a position that there will be some growth disorder that basically is best treated with TransCon growth hormone. Other growth disorder will be best treated with CNP. Some of them will be best handled with the combination, and this is why we can be the leader in growth disorder. And we will continue improving these franchises with lifecycle management and label expansion. But we are not stopping there in rare disease endocrinology.
We have an extremely talented research and development organization, and today we are fueling the pipeline with new product opportunities, building on the same kind of TransCon technologies which have advanced over time. This is why we're sustainable, because we don't need to go out and buy it. We just develop them ourselves. And I'm looking forward in the future to talk about new rare disease product that really will be developed with the same kind of algorithm. After this concluding remark, we will be open for questions.
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. In the interest of time, we do kindly ask to limit to one question and one follow-up. Please stand by while we compile the Q&A roster. The first question will come from Jessica Fye with JP Morgan. Your line is now open.
Hey, guys. Good morning, and congrats on these results. I have one question with two parts. First, I'm curious about the change from baseline AGV for the overall population. Can we just calculate that using the numbers on slide 10 to get an overall change in growth rate for TransCon and for placebo? And then the second part, sort of related to this, when we look at slide, I think it's 11, for the change from baseline AGV for ages five to 11, which I assume would be most comparable to BioMarin's primary endpoint and age group, it looks like the placebo arm here had a positive change in their growth rate, whereas in the Voxzogo pivotal data, the placebo arm's growth rate actually decreased during the study period.
So I'm curious if you could provide the baseline and on study AGV inputs for this five to eleven age group so that we can better understand that cross trial comparison?
Yeah. I, I think I can take the last question, and I think Aimee will help me a lot here with all the different numbers on a very, very early morning. Yes, we tried to do the analysis on slide 11 for the five to 11 years to develop the best possible comparison using the same kind of algorithm that really have been utilized before. We always know it's inter-trials comparison, and but we believe that is pretty valid. Why do we also believe it's valid? When I go over and look at other data, looking on the five to 11 years on height SDS, and I have to see exactly the same pattern. So from their perspective, I feel really, really that is representing and really and strong growth in this patient group compared to the rest. Aimee, do you want to go into more specific data?
... So Jess, you asked on slide 12 from the change from baseline, if one could calculate what the full analysis set would be from the two age subgroups, and the answer is yes, one can. We did not exclude anybody from these. This is, this covers the full analysis.
Thank you.
The next question comes from Tazeen Ahmad with Bank of America. Your line is open.
Hi, guys. Good morning. Thanks for taking my question. I just wanted to get a sense from how you're thinking about the best population for the drug by age. It did look like the kids younger than five had a lesser height velocity improvement or slower improvement relative to the older kids. How should we interpret that? Was that expected as part of the study when you designed it? And how should we think about what a label could look like as it relates to age? And then, what else do you need to complete in order to get your application together by the first quarter of 2025? Thanks.
Thanks, Tazeen. And I think there's two different ways you can look at it. If you look at height SDS, you basically match each subject to gender, to age. And when we looked at that, we actually see the same increase in height SDS. So from that perspective, it's really, really consistent. When you look at annualized height velocity, it's a little bit different because when you see the age group between two and five, you have a heavy, deep acceleration of annualized height velocity. So therefore, you basically have something that's going one way, and then we promote growth in the other way. So therefore, the absolute difference in annualized height velocity will be different. But the real way to compare the growth-promoting effect on our drug is look at height SDS between the two patient subject groups, and there, you basically see the same effect.
The last question, we are finalizing all the documentation. We are for the U.S. application, and it's basically finalizing also the rest of the bioanalytical testing we have done. For example, we are finalizing all the immunogenicity analysis. We know from our phase II data long-term, over many, many years, we never have seen really any immunogenicity. So but all these elements need to be finalized, and then we are writing to get this in as fast as possible to ensure we can come out to the market as fast as possible.
The next question will come from Li Watsek with Cantor. Your line is open.
Hey, good morning, and congrats on the data. Maybe just a couple questions on the next steps. I wonder if you can comment on some of the quality of life metrics or body proportionality, whether you might be able to include that into the label, or whether you need much longer follow-up to have that conversation. And then for the pre-NDA meeting, just wondering what should we expect about the timing, and what are the key issues that you need to align with the agency?
I actually think you have a right view about body proportionality, because typically, you need to follow that on multiple years before you can see a real change in it. So when we looked at the data in body proportionality just for the fifty-two weeks, and we saw how it really improved from baseline, we actually felt really, really, really confident that is really some extremely strong data we have. We will always provide all the data to the agencies, and it will be up to a label discussion if we can get that included anyway in the labeling. And I think this is a little bit too premature to think about how we will describe our labeling.
What we want to provide, we think a holistic data packet that provide a treatment instead of linear growth, as it is in U.S., because we see so many, many different way where we really are helping each person with achondroplasia. Related to other element we need to finalize, we feel pretty ready to go in and be sending in our application here in Q1. We are finalizing everything as we normally should do and get ready to submit it as fast as possible.
And our next question comes from Joseph Schwartz with Leerink. Your line is open.
... Great. Congrats on the strong data. So just to follow on the last question, my first question is, I'm just wondering if you can give us a sense of your confidence that the review process can advance without a hitch, given the delays which we're seeing, in the review for TransCon PTH? Are you taking any particular measures to ensure that you don't experience any such delays again, based on anything that was learned, from the last review at the FDA?
Joe, if you look on my agenda, I can guarantee that is one of the things I really are integrated in the organization. What is the learning from PTH? What can we- how can we ensure that we never, never ending in the same situation, which I don't want ever to do in my life? Having a unique product, but somewhere being stuck in a process. First of all, TransCon CNP is much more simple in a way that is not really being dose titrated.
So just from the basic question about dose overlap, it's really hard to imagine when you only have one single dose. So the simple way to look at that is that we will be in an extremely constructive dialogue with FDA, which we always are. We are already discussing exactly how we are ensuring our CMC section are living up to the latest new requirement from FDA to ensure that we can get the possibility to take it out as fast, as fast as possible to here in the U.S.
Very helpful. Thank you. And can you comment on your assessment of Ascendis' freedom to operate with TransCon CNP, given BioMarin's belief that they control some key intellectual property on, CNP?
Yeah, I have heard a rumor, too, from a lot of different researchers, so I'm still struggling with what it is. I know there is an old patent from... that expiring in 2030, where there was some division being made. When I looked at all the patent, not only me, we have a lot of lawyers, we have a lot of people that look at that, and they come back with one single conclusion. First, they believe that the reissued patents are invalid, and even if it was not getting invalid, we will basically not infringe it.
Basically from the aspect that they're not really claiming TransCon linkers, and it's never been disclosed in this old, old patent. So from that perspective is, I'm really convinced, not only me, but also our entire legal team, external lawyers, that basically this issue is a non-issue. Just a kind of desperation in my view. So from that perspective, I feel really, really confident. I saw how the first part of an appeal went through in Europe. Basically, nearly every claims got removed. There was just the first part of the e-appeal, which are the easiest one for the applicant. Now, the second part is the difficult part for the applicant. So I feel pretty confident.
Thanks for taking the question.
The next question comes from Derek Archila with Wells Fargo. Your line's open.
Hey, good morning, and, congrats on the data. Just one from us. I was wondering if you could discuss your alignment with the FDA on the regulatory strategy for TransCon CNP. I guess, how would it compare to the BioMarin's experience with the Vosoritide and the need for two-year data? Thanks.
Yeah. First of all, we have what I call a standard way to look on our primary endpoint that have been utilized in, I think, 20, 30 years in growth disorder, looking on change in annualized height velocity for one year. It's typical how, to my knowledge, every compound that any impact on linear growth has been, really been evaluated in clinical trial with one-year data. With our interaction, not only with the U.S. regulatory agencies, that it also account other regulatory agencies like EMEA, Japan, every other places, we never have any kind of request for more than one year. Obviously, as you know, we have a lot of supportive data from our long-term trials. I think, Aimee, do we have three-
Yep.
four years now?
Three-plus years. Yep.
We have three-plus years in our long-term data that will be used as supportive data. So I'm not quite sure where this comment is coming from, because it's not coming from the world I'm living in.
... Thank you.
And the next question comes from Gavin Clark-Gartner with Evercore ISI. Your line's open.
Hey, guys. Thanks for taking the questions. First, I just wanted to ask on your broader development plans for CNP. So I believe you have an infant study in the Skytrofa combo study that's ongoing, but I specifically wanted to ask about hypochondroplasia and other indications. Then I had a follow-up.
Thanks so much. You know, you are asking a question which we are doing a lot of evaluation on, and Aimee, she can help me a little bit because as I said, we want to be the leader in growth disorder, and we can be the leader in growth disorder. Because when we just look in an area like hypochondroplasia, it's have a lot of heterogeneity. There is some part of hypochondroplasia which are not really affected by high level of comorbidities, and other are affected with low level of comorbidities. So, what we are trying now to potentially segregate that out and saying some of them would be best treated with growth hormone, and other one will have the most beneficial potential, a combination of growth hormone and CNP.
But Aimee, you're sitting with all this analysis and trying to build in this kind of visionary thinking in all the growth disorders.
So that's exactly as Jan said it, right? We are taking a look at growth disorders, skeletal dysplasias of various types, right? There are numerous out there, and trying to better understand the biology and also the literature out there, right? Hypochondroplasia has also been treated with growth hormone in the past. And as Jan mentioned, as we understand, their main complaint is height in hypochondroplasia, a little bit different from children with achondroplasia who have other complaints, right? Beyond and other comorbidities beyond the short stature. And so through this careful consideration, we are thinking about the best way to take these through development trials, right? Whether it's single agent, combination, comparing, but we will be driven by the biology and what we know out there so far.
Yeah. So we really, you see what we're doing in the growth hormone market. We started with adult, we started with Turner. We're filing the adult growth hormone here in this month here. In Turner, we will have end of the year, the phase II data. It give us the best way to adjust what we call high dose indication, and then we will make definitely basket trial, where we will try to basket many of these indication in one single trial. So we basically in the next three to four years, perhaps shorter time, we hope we can do it much faster. My goal is two to three years. We basically have all indication in the traditional growth hormone market. At the same time, we expanding in all of our growth disorders, and we are now building up the entire...
After we got the data here, exactly how we building up, how we combine it with single agent or combination, or take the best way for the treatment. We're here for do the best for the patients, and this is always our focus. We should not treat a patient with a high, expensive medication if it's not needed, and this is why we really can build out the best portfolio by having the combination of both Skytrofa and TransCon CNP.
Great, very helpful. Just a quick follow-up then on the TransCon growth hormone combination study. As we're looking out to that data next year, what should our expectations be?
You know, I think that is when I saw this growth data, I said, "Do we still need that trial?" This is the question I ask myself, because when I look at the data, if you initiate treatment in the first year or two of life, you will never need to have the combination trials. So the combination trial, basing to the patients or subjects that feel I didn't start sufficient, fast enough, any treatment with our TransCon CNP, and therefore from that perspective is I need to have extra catch-up growth.
There, the combination could help, and this is what we're looking forward to prove later in the year. We basically are enrolling all the patients. It takes us excellent. We have some excellent clinical operation that really talk with all the site every day and really know the patients and the everyone. So we can get this enrolled in. I think it takes us six, seven weeks when we finally got all the regulatory approvals. You saw how fast our trial get rolled in. Just see the time span it took for our pivotal trial here. It was the shortest pivotal trial I ever been part of. So, yes, you're right. It will be for patients that basically has not got initiated on CNP treatment within the first years of life.
Our next question comes from David Lebowitz with Citi. Your line is open.
Thank you very much for taking my question. From a practical speaking, when actually launching, could you run us through the decision-making process with respect to treatment-experienced patients versus treatment-naive patients, and how easy it's going to be to transition patients who might actually already be on Voxzogo, given their label starts at this time at a younger age?
Typically, we see elements that I think you need to separate the geographic different way, because if you just think US, it's some complete special ecosystem in how you basically have patient treatment. If we go to other geographic region, if there is an improved treatment and by discussion with the national reimbursement system, then any physician always take the best treatment. Because when you are into the ecosystem with an approved, reimbursed, full commercial product, there's no restriction in what compound you basically takes. When you come to the US, on long-term basis, every patient basically always get treated with the best-in-class product.
The penetration can some way be delayed in places in the US, as we see with Skytrofa, where there is a lot of resistance in the payer system to get the best possible treatment because of different revenue recognition for the distributor in the system. But I'm convinced that always, every patient should get the best, and we will work in a positive manner to that to happen, to ensure every learning we did it from Skytrofa can be integrated in our commercial strategies for our TransCon CNP.
You know, David, I have a nice story to share from some of our recruitment efforts in clinical trials. So even though some of these children live in countries where a daily therapy for achondroplasia is available, and essentially free to them, they have preferred to instead enroll in our trials, which requires additional visits, right? And time on their part, additional testing, because they have read the data, even from the phase II, and been very enthusiastic about that, and extremely enthusiastic about the once-weekly dosing and safety profile that they have seen from there. So, you know, as you heard earlier, been really straightforward to recruit patients for this trial through the hard work, but also because many of the patients and their physicians out there have found it a compelling approach to follow.
Our next question comes from Kelly Shi with Jefferies. Your line is open.
Congrats on the progress. I have to follow the same line of a growth hormone combo trial. Curious if you have any insights on how much of impact your other growth hormone alone could impact our linear growth for achondroplasia? And also regarding the convenience administration for weekly dosing, how much more expansion you would expect for addressable patient population compared to, like, a daily dosing? Thank you.
I think from my perspective is that we everyone accept the benefit of linear growth. What we see with TransCon CNP, we can provide linear growth with a tolerability safety profile where we can hardly discriminate the two per se. So the barrier for treatment is not high because it's not a major impact on the caregivers and the patient life. It's not like ensuring that you take a daily injection, ensure that the child drinking one third of a liter of water or any fluid before they go to bed, and then try to inject them daily. I think this is why Aimee said that when we recruit a patient, we have to recruit a patient where our access to both commercial products from another daily product, other experimental drugs, but we enrolled in a speed I never seen in my life.
Because the nature of TransCon CNP, there's not really any barrier for the treatment. We hope the penetration will be much higher, but I think it will be partly driven with the benefit we can show besides linear growth. And I think this is where I see we really are addressing all the impacts of the disease, and that is exactly what we want to show. So I think the penetration will be much higher than we have seen before.
... And our next question will come from Paul Choi with Goldman Sachs. Your line is open.
Hi, thank you. Good morning, and congratulations on the data. I want to ask a little bit on the quality of life measures that you list in slide 16. And can you maybe go into a little more detail on whether you saw age differences between the younger patients and the older patients in the study? And then I had a follow-up question.
I, Aimee will go to the details, and I can give you a little bit of my top-level perspective. Because when I see patient-reported outcome, and when you go to a phase II trial, where we basically had little bit more limited geographic out to a phase III trial, and also see how patient-reported outcome are being judged between different geographic region. For example, when I look on Yorvipath, the most impressive effect in some geographic region, when we went to Japan, it was really hard to see it because how to take the question, how to react to it. So what we saw here in our overall perspective, when I look between different region, I see different in this one. When I look on the age group, I don't see any clear trends in this perspective in it.
From my perspective, it is that the PRO always needs to be taken into the context of the different regions. I will not say anything in general. It is easier to get a PRO really to function in the US because there is much more, I should say, a verbal communication about complaints to other geographies, where people are potentially a little bit more quiet on complaints. I think the key element, what we have observed here, we're still doing a lot of other analysis of other elements to prove our beyond linear growth, but the data all align together. What we have seen in phase II, what we have seen in phase III, but we just have a different demographic in our phase III trial compared to phase II. I hope potentially that answers your question with the limitations.
Yes.
In this kind of method.
Actually, this is all the time that we have for questions today. This concludes today's conference call, and thank you for participating. You may now disconnect.