Okay, welcome to the 44th annual healthcare conference. My name is Stacy Ku. I'm one of the biotech analysts, and it's my pleasure to introduce Neil McFarlane, CEO of Zevra Therapeutics. Neil, please take it away.
Thank you, Stacy. Thank you, Cowen, for having us here today. I'm going to take probably about 20 minutes of the time this morning to be able to talk a little bit about Zevra and what we're up to, and then we're going to move into a little Q&A. Before I get started, though, I'd like to let everybody know that I'm going to be making some forward-looking statements, and I refer you to the latest SEC filings. So, Zevra, we are on a mission to become a leading rare disease company, and we're focused in three areas: bringing a team together with solid rare disease experience, executing on commercial excellence to make sure that patients have access to our therapies, and growing a pipeline to bring new products and deliver value to patients. Let me start a little bit with the team here.
What you see is a team that brings a lot of rare disease experience from a lot of the large organizations and smaller organizations that have been masters in the rare disease execution, with product launches also in areas that are overlapping to where we are. We're doing that with strong collaboration with rare disease advocacy partners. On this slide here, you see a number of the areas in which we're focused in, from rare sleep to larger organizations like Global Genes, as well as policy advocacy organizations like the Rare Disease Company Coalition. We partner very strongly with these organizations to ensure that we're working with the advocacy organizations to get not only our products but deliver value along the patient's journey. Let me spend a few minutes talking about our portfolio. This is a very busy slide, and there's a lot going on.
We are a commercial-stage, rare disease company. We have OLPRUVA, which is right now in full commercial launch as of January of this year for urea cycle disorders. We've got arimoclomol, which is being developed for Niemann-Pick disease type C, NPC, and our PDUFA date was recently extended from June 21st to September 21st this year to allow the FDA to have some additional time to review the robust package that we put forth. And we've got celiprolol, which is for vascular Ehlers-Danlos syndrome, and that phase III trial is ongoing. KP1077, our own proprietary formulation of serdexmethylphenidate for idiopathic hypersomnia.
That phase II top-line data is expected in the H1 of 2024, but also want to announce here today that we had last patient last visit that happened at the end of last week, so we're well on our way to achieving the timeline of the H1 of 2024. In addition to that, we had a phase I trial complete last year. That was an IND-opening trial for narcolepsy that will package our 1077 data, along with the idiopathic hypersomnia data to ensure that we've got as much data as we can to inform the phase III program.
Underneath all of that, we've got AZSTARYS, which is partnered with Corium, and we receive royalties and the milestones, and I'm here today to let you know that we did achieve, as we announced in Q4, we did achieve our Q4 milestone payment of $10 million, and that was paid in Q1 of 2024. So what you see here is a pretty busy company, as a small company that's come together in the rare disease space with a portfolio that I'd like to talk a little bit more here now. So commercial excellence, one of the pillars that I talked to you about before.
We've launched, we closed an acquisition of Acer Therapeutics in November of 2023, and, within a six-week period, we hired our field-facing organization, sales, medical affairs, patient services, inside sales, as, as well as, our sales reps, and these folks went through intense training, and certification and hit the ground running in the third week of January. There are, there are a lot of companies that I've been a part of, but not a lot of them that I've hired, trained, certified, and gotten out in the streets to be able to get a product launched, like we have in a six-week period. So I think that goes to show a little bit of the level of expertise that we're bringing to the table, and the folks that we brought on board had 20- and 30-year histories of, of really being experts in the rare disease space.
So, kudos to our commercial organization, our medical affairs organization to getting that done, but we're doing that through rare disease specialists. We're doing that by having world-class patient services to allow patients to navigate the reimbursement journey, and we're doing that with a marketing team that's nimble and executing the types of things that we need to do to get the rare disease message out there in an account management fashion. So I touched on a little bit of medical affairs and patient advocacy earlier, so I won't spend too much more time on that. Our first commercial product, as I mentioned before, is OLPRUVA. It's a nitrogen scavenger, and that removes excess ammonia. The disease is urea cycle disorders. It's caused by hyperammonemia, and it can lead to brain damage or death. This cycle you see here is the urea cycle.
It's got six enzymes and a few transporters. The hallmark of UCD is having these hyperammonemic crises, and they can lead to neurocognitive damage and potential coma and even death. What OLPRUVA does is it actually grabs the nitrogen prior to going into the cycle and allows for it to be metabolized in other ways. Urea cycle disorders is an orphan disease. Today, it's estimated about 2,100 patients in the United States. About 1,000 of those patients are diagnosed, and greater than 800 of them today are treated with other sodium phenylbutyrates. Sodium phenylbutyrates, as I mentioned, there are others that are out there. They do have an unmet need that the palatability, the odor, how it is administered. More and more, our patients and physicians tell us that that affects adherence.
In the next slide here, OLPRUVA has been formulated in a single-dose envelope, not a liquid, not multiple capsules that have to be taken every day, but in a polymer coat, a dual-coated polymer formulation that allows for the product to be put into a glass of water and be taste masked for up to five minutes that allows patients to be able to take this with better palatability, less odor, and ease of administration. The competitive advantages here, as I mentioned, are really as strived by physicians to hopefully improve adherence through this formulation that we have. It's patent protected through 2036, and today, the market is about $350 million of the products that are out there. We've got a growing pipeline, and Niemann-Pick disease type C is the one that we've got arimoclomol being developed.
It's a progressive lysosomal storage disorder, builds up cholesterol in the lysosome that leads to cell death. Arimoclomol allows for increased metabolism in the lysosome and processing of various cholesterols. This disorder is NPC gene mutations that produce abnormal or absent NPC proteins that allow for that cholesterol to be processed. You get the buildup, cell death, as I mentioned. Ultimately, these patients do go on to die from their diseases. It is an orphan indication. The prevalence between the U.S. and Europe is about 1,800 patients, approximately 900 patients estimated in the United States. However, we do know of about 300-350 of these patients that are currently diagnosed and being treated with off-label products. In addition to that, we have an expanded access program in the United States that treats about 70 patients in the U.S.
About 70 patients ex-U.S. It's a significant unmet need. These patients have neurocognitive declines that are irreversible and fatal. The mean age of death in these patients is about 13 years old. As I mentioned, there's no approved treatment in the United States, excuse me, to date. So we're positioned to be the first-line treatment for NPC. It is an oral, first-in-class treatment that can be capsules that are swallowed whole, mixed with food, and have the ability to be, as I mentioned, the first-in-class. Extensive clinical experience with this product. It was developed in a number of other indications. There are over 600 patients that have been treated with the product with no significant safety findings. The pivotal trial that took place a few years that read out a few years back provided with some reduced disease progression data.
In addition to that, I mentioned the ongoing expanded access program and had over 150 patients being treated today in the U.S. and Europe. It's got Orphan Drug Designation. It's eligible for a rare disease pediatric voucher, and today that's approximately $100 million. Our other phase III program that we have ongoing is for vascular Ehlers-Danlos syndrome, and this is a connective tissue disorder that leads to vascular ruptures. And celiprolol is a product that has been designed to reduce mechanical stress on these collagen fibers as they become inelastic and then are prone to dissections or ruptures of the medium and midsize arteries. It is a—it's called vascular Ehlers-Danlos syndrome but also EDS type 4—and it is also a genetic mutation in COL3A1 gene that has been identified.
These patients have vascular ruptures, as I mentioned, of these large to medium-sized arteries, about 25% of patients before the age of 20 and then about 90% of the patients by the age of 40. Mean survival rate in these patients is 48, and usually because of an incident of rupture, leading to sudden death is about 51 years of age. In the United States, there are about 7,500 patients diagnosed in the U.S. with no currently approved treatment options. Currently, right now, the only real treatment option is for you to have a symptom, find it before you have a rupture, and surgical intervention takes place. Celiprolol is approved in Europe for hypertension, and it's actually become the primary treatment for vEDS patients in several European countries. We believe that there's an opportunity to be able to move that program along in the U.S.
So as I mentioned, Celiprolol's mechanism of action is really around vascular dilation and smooth muscle relaxation that allows for the pressure and the mechanical stress that comes on these collagen fibers to be smoothed out, and then you don't get as much wall pressure that leads to aneurysms and ruptures. It's got a pretty unique pharmacological profile that was studied in Europe from the best clinical trial that actually showed about a 76% reduction in the risk of these arterial events in the COL3A1 subpopulation. Some additional data from a longer-term observational study was done in France, and today we are in the DISCOVER phase III trial. It is a decentralized virtual trial with a SPA agreement that is registration enabling, and we'll also have a new chemical entity and ODD. The IP is also out until 2038.
One of our phase II programs that I mentioned that we finalized our last patient last visit last week and are on the path to database lock and driving to top line data in the H1 of this year is KP1077. And this is a formulation of methylphenidate that is serdexmethylphenidate, and we know that idiopathic hypersomnia causes excessive daytime sleepiness. But some of the unmet needs are really still around sleep inertia, which you can't get these patients up in the morning no matter what you do. You can shake them, set alarms, but that sleep inertia, no matter how much they sleep, they still just have a really tough time getting up. And brain fog.
We believe that serdexmethylphenidate can provide an optimal level of exposure of methylphenidate to better address this unmet need in sleep of sleep inertia and brain fog. Let's see here. Let me get to the next slide. So the prevalence is large. It's about 37,000 diagnosed patients in the United States, and we believe that that is underdiagnosed today, and the total population may be much larger. Today, the current unmet need, the current treatments really don't address the needs. There is an approved product for IH today, but the tolerability of having to wake up through the night to take a second dose to then get you the wakefulness that you need during the day and some of the comorbidities of the cardiovascular of having to take multiple stimulants.
With our serdexmethylphenidate program, we've done some cardiovascular work that allows you to get the very high levels of serdexmethylphenidate that you wouldn't be able to get to in the immediate release version of methylphenidate. And then also the potential drug-drug interactions with contraceptives, antidepressants, antihistamines of some of the other sleep agents, you don't have with serdexmethylphenidate. So as I mentioned, KP1077 is a proprietary prodrug of methylphenidate. It is dosed at this time in our phase II trial. We have two dosing regimens that's being done, once daily at bedtime, and then that same dose divided into two, half at bedtime and half in the morning.
We will be reading out, as I mentioned, this data in the H1 to allow us to understand with both the dose finding as well as the design of the study, which was a run-in study to get your dose optimized and then the ability to then do a randomized control withdrawal. We'll have that data, and it'll help us to understand how we move forward into phase III. But this unique pharmacokinetic profile I discussed of being able to take high doses of a stimulant at night, and then about 10 hours later, the opportunity for you to have high doses in the morning when you need to wake up, we believe that hypothesis allows us to be able to address the unmet needs that are still out there. Solid IP, through 2030 and potentially beyond that based on some of the work we've done internally.
And right now, SDX is designated as a Schedule IV controlled substance, and I think that's a key takeaway here as well versus some of the other sleep agents as well as stimulants in the class. Let me end on this slide. I said a lot today about a lot of things that are going on at Zevra as we launch our mission to becoming to bring life-changing therapeutics to people living with rare diseases, but it really does start with the team. We have a strong experience in rare disease commercial launches, a strong track record of bringing drugs to market as well as overcoming some complex regulatory challenges. From a commercial excellence perspective, we're growing these capabilities by making sure we focus on the patient.
What we do every day is understand how we can impact patients and make decisions to improve the lives of the patients that we're here to serve. Right now, we're really working through OLPRUVA. We've launched this product 3 or 4 weeks ago now. We're in the process of learning, gathering information, pivoting, and understanding how we can ensure that we're getting this product to those that can benefit from it. We're also preparing for our arimoclomol launch. As I mentioned earlier, we had a 3-month extension of our review, which we believe will allow us to be able to continue to execute on our commercial launch of OLPRUVA but also continue to make sure that we're ensuring that we have the market access and the market prepared for the launch of arimoclomol as well. Growing pipeline.
It's a busy time, between our PDUFA on September 21st, 2024, Celiprolol's ongoing program, and KP1077 top line results. The next six months will be a busy time for us at Zevra, and I thank you for your time.
So, around arimoclomol and the FDA, curious your thoughts around changing the timing, and obviously in conjunction with that, you had talked about the financial forecasts. So just talk about where you think, that will help you getting around those PDUFA requests.
That's great. So yes, yesterday we announced that we had a extension of our PDUFA based on, actually the agency had been responding to information requests that we got our first information request that we got in January, actually, we've been fielding these requests, and they asked for more time. But I think it's important to take a step back.
You know, we were addressing 3 major areas from our CRL that was, came through in 2021, and the robustness of the package that we had put forth to the agency, in regards to the scale and how we had a modified 4-point scale that we moved forward with, also how to handle the imputed data as well as the confirmatory evidence we provided in our resubmission, new non-clinical data, new clinical data when it comes to natural history of the disease, which we didn't have as much then, as well as the 4-year open-label extension study from our EAP program. It's a longer-term data, and then we were able to really connect all those dots towards the clinical data that came out of the phase III.
So the robustness of our package and the vast amount of data didn't surprise us that the agency needed more time, but that came across from our first IR that we're continuing to be able to answer and field those today. I know Adcom. You asked me about Adcom too. So yes, the agency did reiterate that they plan to bring the product to an Adcom, but they have not given us a date, formally at this point. So we anticipate something prior to the PDUFA date of September.
We talked about right now the independent access program. What it means to the extent that independence flows, level of medication satisfaction, obviously the same activity for some of the patients.
Yes, great.
Well, part of the process of our EAP program, as I mentioned, about 140-150 patients that have been in there, some of them over four years. And about 70 of them are in the United States, and about 70 of them are primarily in Europe. The interesting part of working in this patient advocacy world is how they can activate when they really want to be able to drive forward a program. And when we think about what's transpired with arimoclomol last week, an informal petition went in from more than half a dozen advocacy organizations that came together, almost 1,000 participants between clinicians, patients, as well as their caregivers and family members in support of arimoclomol's PDUFA or approval, I should say.
We feel like between the patient support of not just that informal petition that went in but other advocacy organizations that have also communicated with the agency for the approval, that shows a lot of those patients who've basically said, "I'm on arimoclomol, and it has made a difference to me or my family." We feel that's the strength for us moving forward when it comes to the Adcom, but also the long-term effects that it's had on people over the last four years.
As we think about, let's turn to Twitter.
Yes.
We talked about the authors of the product.
So I think just to provide a little bit more context there and then also to the extent that we can, the different trial findings that we've seen that obviously help us understand kind of different context in terms of what you're going through at the day, what kind of data that is available.
Yeah, so a lot of questions in that one. I'll take them one at a time and see if I can get through them all. If not, remind me. So you asked about the first one, which is their off-label utilization of products in the U.S. There are actually miglustat is approved for Niemann-Pick disease type C in Europe, and it is approved in the U.S. for Gaucher disease.
It is utilized in about 85% ± from what we can see in the patients that are diagnosed in the U.S. Our study studied both those patients, and we had about 85% of the patients in our phase III study on miglustat as well in addition to arimoclomol and the placebo and active arms. So we have some experience in patients having been taken both but also experience in those patients that were just on arimoclomol. That data's into the agency right now. I can't talk much about it at this point, but we're hopeful to be able to get that out later on. The other question you asked me was on other competitors.
We're aware of other symptomatic control competitors that are out there today that are looking at ataxia but not necessarily in ways to be able to stop the progression of the disease, more symptomatology for those patients with Niemann-Pick C that have that symptom. So not necessarily disease halting as we hope that arimoclomol, if it's approved, will become a standard of care and the cornerstone of therapy that can be built on for symptoms.
And I guess to be something we can then discuss, do you expect the drug for them to be used with a basic evaluation in production with miglustat?
Miglustat. So a lot of times with the agency, you get what you study, and we studied patients that were on it and not on it.
So it's our intention that arimoclomol, if approved, would be the cornerstone of therapy. It'd be the only approved product for Niemann-Pick disease type C. and that, you know, physicians can make the case as to whether or not they feel it's important to be able to add to that or, again, in the case of symptom control, be able to also take care of symptoms, like ataxia, accordingly. So those patients today that are on miglustat, we know again of the 300-350 patients that are being treated today, about 85% of them are on miglustat. and we know about 70 of them are on arimoclomol. They're in our expanded access program.
You know, I think it'll be for the physicians to be able to decide for those patients that are de novo that they can get arimoclomol and those patients that are currently on miglustat where arimoclomol makes a difference for them as well.
And then last question is on your, on celiprolol. So in phase III for vascular Ehlers-Danlos, when could we expect that acquisition?
Yeah, so part of our acquisition of Acer Therapeutics, the vEDS program came through that acquisition. You know, it's been 3 months, almost 4 months since that acquisition, and we've been analyzing all of the portfolio products that were there. We believe that continuing to move the vEDS program along made sense to us, so we're continuing to do that in terms of where we are on when that might finish enrollment or where we're moving forward.
I think you got to hold off on that a little bit. We need some more time to be able to dive deep as we reinitiate some certain things and figure out how things move forward. So I need a little bit more time on that one to give you some guidance.