Okay, good morning. Thanks so much for everyone to be joining our 45th Annual Healthcare Conference. I'm Stacy Ku, one of the biotech analysts, and I'm joined by my colleague, Vish Shah. It's our pleasure to introduce Neil McFarlane, CEO of Zevra, who's going to be giving us a presentation today. Looking forward to it. Thank you.
Thank you, Stacy. Thank you, Cowan, for having us. I look forward to spending a little bit of time running through a deck with you today. I'll start by stating that we'll be making some forward-looking statements, so please take a look at our filings, our most recent filings on our website for the most up-to-date information. Zevra has had quite a transformational 12 months. If we think about what we are all about, it's about the opportunity to impact people living with rare diseases. We've got two commercial-stage rare disease products. We've got an advanced clinical pipeline with a phase III program, as well as a phase II program that has read out data. I'll talk a little bit more about that in a minute. We're building an infrastructure to support our future growth at this point.
We have a fairly strong financial position with some updated information that I could talk about later on as well. We are really building the company to impact patients living with rare diseases. If I focus on what our mission is as we are bringing these life-changing therapeutics to the community, there are three really important things that we focus on. One is execution, and we have to focus on a few things, and we have to continue to innovate. The resources that we are actually building today are around four pillars. We talked about this on our Q3 call around our strategic plan. These four pillars are commercial excellence, pipeline and innovation, talent and culture, and corporate foundation. I will work through these as we walk through today's presentation.
On commercial excellence, it's about our ability to synergize our products, supporting the patients that we've got, and building that muscle that allows us to be able to do it again and again after we earn that right. It's about building and innovating on a pipeline that leverages the infrastructure that we have on our commercial business, building a team that's not just rare disease expertise, but people that are built around a culture that really want to make an impact in the lives of patients, and demonstrating that financial discipline with our corporate foundation that allows us to continue to build a sustainable business moving forward. We do that with having the right people around the table.
What you see here in the team, that is the C-suite here, but in addition to all of our teammates, they come with rare disease experience, rare disease product launches, and understand how to be able to make that impact for patients. I want to talk a little bit about the portfolio because this is really how we're going to deliver that value. Most recently, we've got an approval of MIPLYFFA, which has been developed for Niemann-Pick disease type C. We got an approval in September of last year, and we put the medicine in channel at the end of November, and with solid intellectual property as well via orphan drug exclusivity. OLPRUVA, which is a product that we acquired out of our Acer transaction about a year, a little over a year ago, and that is for certain urea cycle disorders.
That product's been launched, and we have great synergies between both of these commercial assets that allow us to be able to leverage an infrastructure that is quite lean on the commercial side. We've got a partner product in AZSTARYS, which was developed by the company, and we collect royalties and milestones from the sale of AZSTARYS through our partner. On our pipeline, I think importantly enough, one of our catalysts coming in 2025 is around how do we expand our MIPLYFFA Niemann-Pick disease type C program XUS. We're exploring regulatory pathways in Europe and other countries, and understanding our MAA filing and how we move that forward will be our next big catalyst in 2025. We'll come back to you and let you know more about that as we uncover the appropriate approaches to take there.
With CELIPROLOL, that's a phase III program being developed for Vascular Ehlers-Danlos syndrome. That's an ongoing trial, and we're enrolling those patients. As we mentioned in our Q3 call, we restarted enrollment, and we'll be talking more next week on our earnings call about the updates in Q4. The phase II program I mentioned earlier on was KP1077. It was being developed for idiopathic hypersomnia as well as narcolepsy. We actually delivered our end of phase II or our phase II data, which was positive, and then we went to an end of phase II meeting with the agency. We have a pathway forward for a single pivotal trial and understand the safety data that we need to collect as well in the 1077 program.
However, we're looking for strategic alternatives for that program versus doing it ourselves because the end goal of being able to provide a commercial infrastructure that would be able to adequately get KP1077 to those patients in the sleep space is a much larger infrastructure and not really provides this, doesn't really provide the synergies that we're looking to try and continue to develop and leverage with our commercial infrastructure for MIPLYFFA and OLPRUVA. We are in the process of doing that right now. Let me switch briefly and focus on what is near and we're executing on, which is around our commercial infrastructure. We've got a very efficient team that's providing access to our medicines that are commercially available today. It starts with our rare disease specialists. We've got the marketing support.
We've got patient reimbursement services, account management, and from a national payer perspective, as well as from a regional payer perspective. We surround that with very solid medical affairs and patient advocacy in this space of rare disease, which is critical to impacting small disease populations. We've got a program called Amplify Assist that makes our, it's a comprehensive support system for getting patients on an individualized basis through this challenge of getting medicines to patients through the payer coverage, through education and disease state education, as well as some personalized insurance coverage. We work through that process through our Amplify Assist program for both of our products, which I think is an important perspective as well. We do that for MIPLYFFA and for OLPRUVA and get some synergies out of that as well.
I'm going to spend a few minutes talking about MIPLYFFA, our most recent launch, and you can take a look at the prescribing information for all of the key data. Based on the next 15 minutes or so that I've got, I'm going to whip through a few of these. MIPLYFFA is indicated for use in combination with Miglustat, and I'll tell you why the benefits of that in a moment and the clinical data that we have there are so important for treatment of patients two years and older with Niemann-Pick disease type C. The reason you see these different colored boxes is because it's a weight-based therapy. It's given orally or via feeding tubes three times a day in various dosages that you see here.
Quickly about Niemann-Pick disease type C, it's a neurodegenerative lysosomal storage disorder, builds up of cholesterol in the cell, and this progressive buildup of lipids in the cell leads to cell death. Ultimately, based on when you present earlier, you may have more visceral-type implications of the spleen, liver, and the brain, but actually the older presentations, you may see more issues with the brain. It results in loss of cognition, speech, the ability to swallow, fine motor skills, ambulation, which is also part of the tool that is utilized to be able to show disease progression over time. Once you lose these skills, you don't get them back.
Moving forward, about 1,800 patients from a prevalence perspective between the U.S. and Europe, about 900 of those patients from a prevalence perspective in the United States, and approximately 300-350 patients are diagnosed or treated through some work that was done previously through ICD-9 and ICD-10 codes in the United States. I mentioned that you can have onset at any age and the differences between earlier onset and later onset. There is more to that, but for the sake of time, I want to move on to some of the data. The average age is around 13 years old in terms of mean age of death.
About 80% of the patients that we've seen in all clinical trials, whether it be ours or others, and the experience we've seen in our Expanded Access Program are on Miglustat, and it's a primary treatment and approved for use in Europe, but not in the United States. As we move to the next slide, I mentioned, and I'll mention this in more detail around the efficacy data that we saw around 12 months of treatment, the NPCCSS, which is the only validated score that allows for the progression to show the progression of the disease. We saw halting of the progression of the disease with MIPLYFFA in combination with Miglustat, and I'll talk about this in a moment, versus a two-point progression of disease, which is significant.
A one-point progression of the disease can actually mean the difference between somebody ambulating or being in a wheelchair or the ability of them having to feed themselves or needing to be fed by others. It is a devastating disease. From a safety perspective, very well tolerated, adverse effects were mild and moderate, and you can see this in the prescribing information. We have actually had a long timeframe of patients who have been in the clinical trials to the open label extension to the Expanded Access Program, and then all the way through now, now converting to commercial drug. Over 270 Niemann-Pick disease patients between our Expanded Access Program in Europe as well as our Expanded Access Program in the U.S. have been treated. We have quite a history from a safety perspective.
I mentioned the dosing three times a day, and I also mentioned some of the differentiation and efficacy data. Let me get into that in a little bit more detail here. I mentioned to you, if you look at this chart on the bottom left, what you see in the rising bar over 12, rising line over 12 months is progression of the disease with a patient who is, and 80% of these patients, actually all of these patients were on Miglustat only. You add MIPLYFFA, and what you see is no progression of the disease or even halting of the disease through 12 months when you add Miglustat and MIPLYFFA together. I mentioned that this is the revised four domain NPCCSS, and one point of progression is meaningful. Two points of progression is life-changing for patients.
We're happy to be able to provide MIPLYFFA in combination with Miglustat to these patients. On the right-hand side, you see the safety profile, well-tolerated safety profile. As I spoke about earlier on, this is information through October 31 that we announced on our Q3 call. Of those 300-350 patients, we had 90 prescription enrollment forms. Physicians enrolled patients for MIPLYFFA in the first five weeks post-launch. Sixty-nine of those came from our Expanded Access Program, and 21 of those patients, importantly, were new patients de novo to MIPLYFFA and were outside of our EAP. The statistic on the bottom, all of these are dated because they're through October 31. We'll provide more information next week in our earnings call.
At the time, October 31, approximately five weeks post-launch, we had about 30% of the prescription forms at that point that had been approved for reimbursement. You can imagine we have more prescription forms. We have more enrollments and more coverage determination as well that we'll talk a little bit more about next week. I also mentioned that the next major catalyst for us is also understanding the regulatory pathway for an MAA in Europe. We've been working through the FDA documentation to be able to understand how the best approach is to reestablish our application in Europe. We're not ready to let folks know what's transpiring there yet because we're still working through that internally. Very soon, we'll be able to announce a pathway.
In Europe, importantly, we have about 70-80 patients that are in compassionate use in Expanded Access Programs today that are being treated with arimoclomol. Through the French program that allows for pre-commercial sales, we net about $2 million per quarter out of that program. We plan to continue to have arimoclomol and hopefully MIPLYFFA in Europe shortly for patients across the continent. I want to skip quickly to the program that we launched earlier, about a year ago, actually, this time last year that we launched after acquisition of Acer Therapeutics. it's OLPRUVA. The prescribing information is available online. This has been developed for certain UCDs. There are about six enzymes and a couple of transporters that process ammonia and nitrogen out of the body.
When you have defects in some of these enzymes or transporters, you get buildup of ammonia and nitrogen, and you actually get neurotoxic and cognitive damage that actually is irreversible. There are nitrogen scavengers that are out there, or a number of them that are out there. OLPRUVA has been developed as one of those nitrogen scavengers that's got a clinically differentiated profile that we're offering for patients. The marketplace in the U.S., about 1,100 patients diagnosed, approximately 80% of them are in the enzymes that we are approved for, which gets to about 800 patients receiving therapy in the U.S. The important part is of those 800 patients that are receiving therapy, still 25% of them or so have hyperammonemic crises, and a lot of that is based on adherence. OLPRUVA was, and I'm going to skip to the next slide here.
OLPRUVA was developed through a 505B2 filing pathway, but to be able to actually provide some of the differentiation to some of the products that are out there today, which I'll talk about in a minute, and had a safety profile that's consistent with the other sodium phenylbutyrates that have been on the market for decades. The dosing is one of those areas that is actually a differentiation. It's a convenient single-dose envelope, and we call it ammonia control on the go. It was developed to be able to have palatability and adherence type of differentiators, one being that you can actually put this, dissolve it in water, and was designed to be taste masked for up to five minutes and provide that palatability that patients don't have with some of the current therapies that are out there today.
As I mentioned, poor adherence, recurrent hospital visits, and patients that are not optimally treated or have mild diagnoses that do not take medicines, or they may have diet or other areas that they do to control their nitrogen buildup. These are some of the real reasons why OLPRUVA was developed. As I mentioned, we are driving this adoption of OLPRUVA in multiple avenues, but we pivoted our strategy in Q3 to those more active adult patients that are looking for that ammonia control on the go. They were missing their midday doses because they had to pull out an OLPRUVA and take it in the middle of their day. We wanted to be able to provide a more discreet therapy for these patients and a more private opportunity for them to take their and manage their ammonia. We are working through that strategy right now.
We'll have more in terms of the adoption of that strategy as we get through the next couple of quarters, and we'll talk more about that on our call next week as well. I want to quickly, in the last few minutes that I've got, talk about our pipeline. One is CELIPROLOL. CELIPROLOL is a program that's being developed for the treatment of Vascular Ehlers-Danlos syndrome, which is a connective tissue disorder, and it's the most severe of the Ehlers-Danlos syndrome subtypes. It's caused by a COL3A1 gene mutation. It leads to defect in the vessel walls of arteries as well as hollow organs. You can have aneurysms, you can have dissections, or you can have ruptures of hollow organs with this connective tissue disorder. There's a significant unmet need for vEDS.
In the United States, there are no approved, actually, there are no approved treatments in the U.S. or in Europe, but I'll talk a little bit about that in a moment. About 7,500 patients in the United States live with vEDS, and about 95% of them are genetically confirmed COL3A1 diagnosis. So about 25% of the patients experience an event before the age of 20. 90% of these patients will experience an event by the time they're 40. Their median age of survival is 51 years old. Quite frankly, the only treatment today is surgical intervention if you know that you have it and you're monitored to see if you can fix the ruptures and catch them ahead of time. The one thing I mentioned a moment ago, there's no approved treatment for vEDS in the U.S. or Europe.
However, CELIPROLOL was approved decades ago and found to be effective in vEDS patients in Europe. It is the standard of care in several European countries today, but it is not available in the United States. Talking a little bit about the potential treatment of CELIPROLOL for vEDS patients, it's designed to reduce the mechanical stress of that constant pressure that comes on the arterial walls. It's a selective adrenergic modulator, and the mechanism of action is thought to be through Vascular dilation and smooth muscle relaxation so you don't have that pressure buildup on the walls, and that leads to then a rupture. There is quite a bit of data that's been developed on CELIPROLOL throughout the years. There was the trial called the BEBES trial that showed improvements with CELIPROLOL versus non-treated patients. There's long-term French data that was put forth also showing benefits.
There's an observational Swedish study that showed benefits, and then our DiSCOVER trial, which is ongoing right now. There is a lot of data out there showing that CELIPROLOL has the ability to impact vEDS patients. We are running this trial. It is a 150-patient randomized decentralized trial, and we have started re-enrolling patients after a hiatus from the previous sponsor at the end of Q3. We will talk a little bit more about our path forward as well as impact on what we have done over the last quarter on our call next week. Switching gears very quickly to KP1077. This is the program that serdexmethylphenidate we were developing for idiopathic hypersomnia. Idiopathic hypersomnia is a devastating sleep disorder that is debilitating by nature in regards to just being chronically tired. It is characterized by excessive long sleepy times. You still actually never feel refreshed even after long naps.
It is usually measured by the IHSS, which is the Idiopathic Hypersomnia Severity Scale or the traditional Epworth Sleepiness Scale. I am going to quickly run through this because I am running out of time. There are approximately 37,000 patients in the United States with IH. About 66% of these patients still report symptoms of not being treated well enough and have excessive daytime sleepiness, brain fog, so on and so forth. About 85% of them need more than one therapy, and the current treatments just do not seem to address the needs. Let me tell you a little bit about our program. Serdexmethylphenidate is a proprietary prodrug of D-methylphenidate.
We looked at two different dosing regimens, once a day at bedtime at very high doses that then allowed for patients to be able to get their doses elevated throughout the evening and then get a high dose of stimulant on board approximately 10 hours later when you're trying to get patients up, which is what they have a lot of times with the sleep inertia that they get. We looked at both the safety and tolerability of existing treatments, and we saw some greater tolerability, some lower cardioVascular effects. There is no drug-drug or there's limited drug-drug interactions with other, unlike other sleep areas. There are some real differentiators that we bring with serdexmethylphenidate. It's got orphan drug exclusivity.
The important part here is you see some of the data on the right-hand side, which was very encouraging for us to be able to go to an end-of-phase II meeting with the FDA at the end of Q3 and allowed us to be able to work with them on a path forward for a single pivotal trial with collecting the appropriate safety data that will allow us to be able to move forward into IH and the potential to expand into narcolepsy. After looking at both the clinical development pathway as well as the commercialization needs that we have, it just doesn't have a fit that we have with what we're currently doing in the ultra-rare 40 centers of excellence, the high synergies that we have versus the sleep space, which is a slightly different, it's a different call point than what we have.
We decided that we would look for some strategic alternatives, and we're exploring that with outside parties today. I am going to stop in one minute and let you know that this data that I'm showing you right here was as of Q3. We talked about having approximately $95.5 million on the balance sheet at the end of Q3. Obviously, this data is a bit stale. What I can tell you, though, is that last week we announced a definitive agreement to sell the pediatric or the priority review, the pediatric priority review voucher that we received with the approval of MIPLYFFA for $150 million to an undisclosed party. We're working towards closing that in the next 30-45 days. With that, we feel like we're in an even stronger position from a corporate foundation perspective.
I'll leave you with, we believe that Zevra is a unique opportunity for not only patients that we serve, but also for investors that are looking in investing in an organization that's got two commercial rare disease programs. We've got a pipeline that is both late stage, which we believe is de-risked from a clinical perspective, and we'll do the trials accordingly. In addition to that, also discipline that we understand if we start something in a phase III program, we've got to be able to commercialize it and are looking to be able to find the appropriate partners for 1077 for a phase III ready sleep program. We've got an infrastructure here that's supportive of future growth.
We have two programs that we commercialize with a very lean infrastructure, and our goal is to be able to execute what we have today and earn the right to potentially leverage our commercial infrastructure in the future. As I mentioned, between commercial revenue, royalties, and milestones and the monetization of a PRV, we feel like we are in a strong position to be able to execute our mission. Thank you, Stacy.
Wonderful. I want to make sure you all are given the opportunity to ask some questions. If not, we certainly have a few.
What's the support for the infrastructure you're building?
The question was, how many programs do we think we can support with the commercial infrastructure and the infrastructure we're building in the rare disease space?
I'll say to you that when we think about where we are today and the synergies with about a dozen people on the ground between sales and commercial, and then we also have reimbursement specialists that we ramp up and down through a contracting organization that we work with, that if there are 40 centers of excellence that we call on today that are the vast majority of these lysosomal storage diseases, we can add additional programs into our infrastructure today to commercialize it with our back office, our specialty pharmacy, our hub solutions, all of the other things pretty easily. What we have to do right now is execute on what we've got in front of us and earn that right.
How many NPC patients in the U.S. are on miglustat?
The question was how many patients in the United States on miglustat and the typical duration of treatment. Did I get that right? Okay. What we know in terms of miglustat utilization is based on our clinical data, our EAP data, other clinical data from other competitors that have been out there and other programs that have been developed. Approximately 80% of all patients have been on or are on miglustat or have been on miglustat throughout their journey. What we understand from physicians and patient advocacy groups as well as patients is that the safety profile of miglustat and its sometimes GI effects that it has, patients will dose up and down throughout, but they'll try to stay on miglustat as best they can.
Of the 300-350 patients, our best guess is that 80% of those patients are on miglustat and remain on miglustat based on the safety profile.
It might be helpful for you to maybe comment on the patients that you're kind of seeing get on MIPLYFFA. It sounds like you do have some patients that are de novo and obviously a little outdated information, but maybe comment on what we're seeing as we think about maybe those that are diagnosed and treated and maybe those that are undiagnosed and could really enter the funnel.
Great question. We are pulling out all the stops from our educational perspectives, our genetic testing perspective, all the things that we're doing to be able to make sure that we're educating people that MIPLYFFA is available as a cornerstone therapy in combination with miglustat.
When we looked at our Q3 data, that again, first five weeks, we saw that there were both newly diagnosed patients, patients who were converting from our EAP program, and those who had never been on the program before. We'll talk a little bit more about this next week, but what I can say is that we continue to see enrollments coming in in those buckets as well. Continuing to have conversion from our EAP patients, continuing to have de novo patients, and continuing to have newly diagnosed patients as well, which I think is that unlocking of the 300-350 to the 900 patients that are from a prevalence perspective. It is early in the launch. I'm incredibly grateful and pleased with our team and the support from the patient advocacy organizations and all of the people.
It takes a village to unlock and provide these therapies to patients. I have to tell you, the launch to date is exceeding my expectations for sure.
Wonderful. To exceeding your expectations, that comment, maybe for some context, provide your original expectations for maybe when your EAP would have been kind of run through, so to speak, and maybe latest public expectations around when that would close.
Okay. Great question. Two things. One is we had 83 patients that were in the EAP when we got approval and the program was no longer enrolling patients.
We actually had about a dozen, I'm going to say about a dozen, because I can't tell you the exact number because I don't know what the, and I can't remember what the exact number is, patients that after our advisory committee and the strength of the vote of the advisory committee, there was a bit of a rush to patients wanting to get into our EAP program. We went from approximately 70 patients in our EAP program up to 83 once we got approval. That was also telling. In a lot of other rare disease drug launches that I've done and others in our organization usually take about 12 months to get your EAP patients converted. The expectation going in was that we would see something similar to that. What I mentioned on our Q3 call is that actually we accelerated that and we brought that in.
We think that we're going to be able to, at that time in Q3, which we announced, and we'll tell you the update next week, that we felt like we'd bring that into the end of Q2, which was less than a year. The expectations of trying to transition all those patients within a year, we now feel, we announced in Q3 that we felt we could do that by the end of Q2, and we'll have an update for the public next week.
You kind of started by saying you are really focused on the XUS opportunity. Maybe add a few more details there. Where are you in the boots on the ground kind of approach?
If I bring the audience back, the product was originally filed in Europe first from the previous sponsor and then taken back at withdrawing the application at about the same time the FDA provided the U.S. with the CRL. We knew what the issues were and we knew what the U.S. issues were. They were very similar, and we worked over a couple of years to get the new data that would allow us to be able to get a successful regulatory approval in the U.S. Now we're taking that data and actually understanding how we can position that for an MAA. That has been the work since all of Q4. Today, the team is doing extraordinary effort in trying to bring the most efficient package we can and understand how we can get this product to patients in Europe.
About 1,000 patients in Europe, 1,100 patients in Europe, as I mentioned in the presentation. Miglustat is approved in Europe, and I think much more of a mature market. There are more patients that are treated and diagnosed because they've got an approved product. We're hopeful to be able to bring MIPLYFFA to those patients and then have a cornerstone of therapy and halt the progression of the disease just like we did with the FDA label.
Wonderful. Any final questions? Okay. With that, I think we're at time or a touch over. Thank you so much.
Appreciate the extra time.