We're going to go ahead and get started. Thanks again, everybody, for joining us this morning at the Citizens Life Sciences Conference. Really pleased to be joined next by Zevra Therapeutics CEO Neil McFarlane, CFO LaDuane Clifton. Zevra is a company focused on developing and commercializing therapies in the rare disease space. The company has a portfolio now of approved products. The one we're focused on most near term is MIPLYFFA for Niemann-Pick Disease Type C, which was launched towards the end of last year. Our view has been really impressed by the launch so far. Welcome, Neil and LaDuane. Maybe I could just ask you to give a quick 30-second intro.
Yeah, thank you. LaDuane, quick intro.
Hello, I'm LaDuane Clifton. Been with the company for about 10 years. I think this is a very exciting time for the company as we've got two commercial products, product of a lot of strategic planning over time. Seeing it come together along with a very solid corporate foundation has been a great journey.
Shall we go on?
Sure.
Let's make it happen.
I mentioned that MIPLYFFA launch has gone really well. Can you maybe just give us the background to the product, a little bit of an overview of the clinical profile and how you approached the launch last year?
Yeah, thank you. We are really pleased with the work that happened prior to launch, leading up to launch, and then the launch for a rare disease, as you mentioned, Niemann-Pick Disease Type C, which is a lysosomal disorder. You get buildup of cholesterol in the cells, which leads to either visceral presentations in the early diagnostic phase or more psychiatric presentations in the later phases of the disease. MIPLYFFA, as you mentioned, was approved in combination with miglustat in September of last year, and a great breakthrough for patients having the first product ever approved in the United States for Niemann-Pick Disease Type C. With data that is quite strong, in combination with miglustat, we see that you have approximately a two-point difference between miglustat alone and the progression of the disease through the Niemann-Pick Type C Clinical Severity Scale, and then actually halting of the disease. When you think about neurodegenerative diseases that continue to progress, the holy grail of what patients, families, and physicians want to see is how can you halt the progression. That's what our data says through 12 months based on the NPCCSS with a very acceptable safety profile.
Right. So a true disease-modifying profile.
Absolutely right.
Can you just give us a little bit of background on the disease? You said it's a lysosomal disorder, but how many patients are there? Where are those patients? What are they treated with today? Understanding that you were the first FDA-approved therapy.
Right. In the United States, there are approximately 900 patients from a prevalence perspective. Of those 900, 300-350 of them have been diagnosed. Importantly, the data that I mentioned that's in the FDA-approved label does not also mention the fact that we've had an ongoing expanded access program for patients up to five to seven years, both on efficacy and on safety. This data and the strength of the data and over the long duration of therapy, I think, has been part of the success that we've had from launch to today.
Great. You mentioned the EAP program. You have successfully and rapidly transitioned patients over now to commercial drug. Reimbursement is never easy, right? Can you speak to just how that process has been and what you have done to help patients get onto therapy and get onto reimbursed therapy as quickly as you have?
Let me start with the EAP program, because I think this is an important component. As I mentioned, the longevity of the data really differentiates MIPLYFFA from anything else that's out there and that's been developed to date. We traditionally had about 70-80 patients in our EAP. After we had our advisory committee last year and the strength of the data came out and the support from the advisory committee and then leading to approval in about a short period of time, about a month thereabouts, we had a rush of patients who we like to say these are the really in-tune patients. They're patients who are in the patient advocacy orbit. They are patients who are wanting and willing to get into clinical programs like an EAP.
We had this half a dozen patients that came in at the very tail end that were trying to get into our EAP prior to approval. Once we had those patients, we started to be able to then work with the sites. We had about 13-14 EAP sites. Patients had to go to the site to be able to get their previous quarter's worth of medicine. We were able to get that down to about a month's worth of medicine. Patients were being seen on a regular basis.
That really allowed us to catapult our transition of patients from the clinical program into prescription enrollment form that would then actually lead through reimbursement and then patients on commercial product while supporting them through patient services, while supporting them with field reimbursement, and then obviously while supporting the education of the payers when it comes to the strength of our data and why it's so important for patients to be on a disease-modifying therapy.
Great. Can you speak to what you've heard from physicians early in the launch? Obviously, there's physicians that have used the drug before, have had patients in the EAP, but you've also had patients that are new to therapy since the launch. What are you hearing from physicians about what attributes of the drug they like, what they're seeing in patients in the early experience?
I think that having launched a number of rare disease programs and been in the pharma industry for a while, you always get the same things once you launch a program. Physicians say, I need more data before I prescribe it, or I need more safety data, or I need more efficacy data. For us, it was a challenging time to get MIPLYFFA to the marketplace. It also allowed for us to continue to invest in this long-term data set. When you come to market and you have data that's not just 12 months in a disease-modifying label, but you have five years' worth of longitudinal data and patients and physicians who've had experience, it lends itself to those physicians who know that in the rare disease space that have heterogeneous presentations, you need multi-therapeutic avenues in order to be able to treat these patients.
You have got those physicians now. We have heard from those physicians that they are now able to be able to drive both with miglustat and MIPLYFFA, which is one in our label, and look at the modality of therapies that they have more than one to work with. The opportunity for those physicians who are seeing patients and getting them for the first time on a disease-modifying label comes with very different types of feedback, which is a lot of times education that our medical science liaisons and our field representatives are doing on the data itself. They have never utilized a disease-modifying therapy.
It's a bit of the folks who've been there, who've had a long duration of therapy on MIPLYFFA and miglustat, and then those who are new to therapy that we're having to educate, both the physicians, the office staff on how to move forward with, especially pharmacy, and then pulling patients through to the bottom. Our efforts are paying off. As you mentioned, through the end of Q4, we had 109 prescription forms and prescription enrollment forms that came in. That's approximately a third of the diagnosed patient population. Next week, we'll be announcing earnings for our Q1 number, which we'll be pleased to share next week.
I will not ask you that number now. You mentioned basically 1/3 of the diagnosed patient population now has a patient enrollment form. And a lot of that, a good portion of that was in the EAP. How should we think about the cadence moving forward of new patient adds? I mean, of those remaining 200-250 patients, how well identified do you think they are? How accessible do you think they are to go and get on drug?
This is part of our learning. This is part of what a launch is all about. As we have now started to expand beyond our EAP, which again, are these very engaged patients, families run through walls to try and get anything they can for their families. There are also families who have been treated for just symptoms. You may have had epilepsy as your symptomatology. You may have had some visceral symptoms and only treated with symptoms. That is why it is important that we continue to educate, do our disease state education, get our reps out there and making it happen, and driving. Our media campaigns that have been moving forward have been incredibly touching. Our earned media profiles that have been going out have been picked up nationally on the national stage. We launched a new disease state awareness campaign that has got really good insights.
Next week, Josh will talk more about some of the benefits that we're seeing there. It's not just about the 300-350 patients. We're also seeing newly diagnosed patients now as well, which is a very different learning for us. It's the 350 to the 900 patients that we're seeing as part of this global U.S. campaign of disease state awareness and making sure people know there's actually a product available for these families now. That opens up new doors. We're seeing newly diagnosed patients as well. Different learnings for different segments, if you will.
Clearly, part of the answer to this question is that there has not been an approved therapy before. Why is the diagnosis rate as low as it is? What does that tell you about how you can get that diagnosis rate up? I mean, I am not sure there is an answer to this part, but can you get to 600 diagnosed patients? Can you get to 900 diagnosed patients? What are the pulls and pushes about finding as many patients as possible for the therapy?
There is a marker that we utilize and something that actually has already been done as a comp that we like to be able to share. In Europe, there are about 1,100 patients from a prevalence perspective. We know that based on our work and based on some of the publications that the size of the diagnosed patient population in Europe is much higher than that in the U.S. A lot of that is attributed to the fact that they have had an approved product in miglustat there for a decade. We have seen this gap between the diagnosed patients and those from a prevalence perspective through disease state education and through awareness campaigns really drive towards the prevalence number versus towards the diagnostic number we see in the U.S.
That comp for us gives us a lot of confidence that our ability to be able to now have a product approved, now get the disease state education out there, and really drive towards all of these varying things we announced on our Q4 call, genetic testing availability, obviously all the media work that's happening. The media work is really important. I can't tell you that as a rare disease company with a rare disease business model where we have a very focused footprint, about a dozen people between medical affairs, sales, patient services that handle our centers of excellence for MIPLYFFA, we need the ability to have surround sound and people who pick it up and do it for us as well. Some of these earned media that's come up has come into not dozens of markets, but over 100 different markets nationally across the United States. That is how we are going to amplify our voice. That is how we're going to continue to make sure we execute on this rare disease business model.
Can we talk a little bit about miglustat? Your label specifically speaks to the combination of the two products. How has that impacted the launch? Helped or in any way pressured the launch? Do you expect to see more patients go on to miglustat now because MIPLYFFA is approved?
I can't answer the second part of that question if more patients will go on to miglustat. What I can say is that the experience we've seen through our specialty pharmacy and the enrollment form for MIPLYFFA, again, we are commercializing MIPLYFFA. The label says our prescription enrollment form says, MIPLYFFA, what dose do you need? How many times a day? And are you on or have you been on miglustat? Check that box. We don't promote it per se because it is off-label. I do think that our early experience has shown that because there's a large percentage of patients who are on miglustat, we see between 60% and 80% in all the data or have been on or on it, that prescribers to get an unapproved, off-label product that is not cheap through a specialty pharmacy system, they have experience.
That experience helps us when we now bring a product that shows you a label that says miglustat alone, here is the progression of the disease, miglustat and MIPLYFFA together, you halt the progression of the disease. That education for us and the ability for them to then go out and do another specialty pharmacy order for a product that has a potential to impact the disease course, we believe it is very helpful.
Let me ask the question a different way. Looking forward, how much monotherapy use of MIPLYFFA do you expect to see?
I can't answer that on what we expect because this is really early in the launch. What I can tell you is that we have had and seen patients who have been on monotherapy or have been on miglustat before and unable to tolerate it. Physicians have been willing to actually put their patients onto MIPLYFFA. I mean, in our own clinical trials, in our phase three clinical trials, only 80% of the patients approximately were on miglustat. We had, although it was a small number of patients and hard to read into what that data is, patients that were not on miglustat, it happens.
Still early in the launch, but you said on the Q4 update that you are seeing patients getting refills. When you think about the patients that are new to drug, are you seeing refills in that population? I guess, when can you start talking about what the persistence rate is on the drug?
Really too early. Five weeks is all we had of medicine in the channel at the end of Q4. Obviously now we have a full quarter. What I can tell you, though, is that our expanded access program has shown us that patients, when they get onto MIPLYFFA, stay on MIPLYFFA. Again, up to five years in the data. You saw this in the advisory committee meeting and the patients who have talked about the impact that MIPLYFFA has made on their lives and on their child's lives. We see a huge level of consistency in that 70-80 patients that we had in the U.S. Actually, we ended at 83 patients. In addition to that, we've had a global EAP program running in Europe.
In our European global, we call it our global EAP versus a U.S. EAP, we've had 70-80 patients consistently now also for a long time. When we think about persistency and compliance, the best comp we have is actually our EAP patients who, by the way, they have to run through hurdles to go to the site every quarter to get data generated and to do all those types of things. It's a real blessing that these patients do that, but they continue to do it for a reason. We think the compliance rate, that's our best comp that we've gotten. We expect with the safety profile that we have for the product that we'll see that in the real-world experience play out.
How do you think about the European opportunity for the drug given that miglustat is approved there? What are your regulatory submission plans and commercial strategy in Europe?
To lay it out, about 1,100 patients in Europe from a prevalence perspective, a lot more diagnosed patients. I can't give you an exact, but it's a lot more than the U.S. And miglustat, which has kind of been there in the marketplace for some time. As we think about our data out of our phase three and that you had miglustat versus miglustat and MIPLYFFA and the split, as I mentioned, we're now talking about the opportunity to bring something that can help patients in Europe as well. We took the FDA package. We then went to two different outside consultants to help us to address some of the grounds for refusal that came through previously. Now with all this new data, we announced on our Q4 call that we'll be filing our MAA in the second half of this year.
In addition to that, we're going to continue to expand on our EAP program in Europe to make sure that patients now with an FDA label and the data that's out there, that we'll be able to continue to drive patients into our compassionate use programs. When I think about the market opportunity in the U.S., and if you just go with the 300-350 patients that are there today and a much larger number of patients who are being diagnosed and treated in the U.S., we see the TAM of about the same. Even if you calculate the fact that in Europe we would expect to see a lower price, you see a faster penetration because there's more miglustat that's been utilized and larger patient numbers.
As we're ramping the U.S. market and again, exceeding all expectations, nobody in this company, maybe I think maybe you might admit this too, but I'm not sure if you can, we're exceeding expectations by a long shot in terms of how fast we've transitioned the EAP and brought on de novo patients. We expect that with a European label, we can actually do that even faster because there's more patients that have been diagnosed.
We have written multiple times that you're exceeding expectations. And that's on management too, this great execution. We've written that too. No, it's been a great launch. Another thing that I think is really important right now is balance sheet, cash runway. Part of the MIPLYFFA approval came with a PRV. You very successfully monetized that at a higher value than I think anybody was expecting prior to the approval. Can you just speak to cash position, how you think about how that enables you to continue to execute on the MIPLYFFA launch?
We're in a very good position, as you noted. We reported out that we were sitting at, with the PRV sales that came in on April 1st. We already reported our cash balance. We were at $68.7 million. We got net proceeds of $148 million. It put us at $217 million of cash on the balance sheet. That puts us in a great position to continue supporting the launch and making sure we execute and focus on getting the MIPLYFFA launch, taking care of all the activities that Neil just mentioned, continuing to support all OLPRUVA launch, and also working to accelerate the rate of enrollment in our celiprolol program, which is our phase three for vEDS. We have all we need to do that. We look forward to just seeing how we continue to execute, look how these revenue trends change, and then we'll see where it goes from there.
With that backdrop of a really strong cash position, Neil, over the last couple of years, you've really focused the company on this portfolio of rare disease assets. You've prioritized within both the commercial focus and the pipeline. How should we think about looking forward how you're going to continue to generate or build shareholder value? Are there more assets that you could bring into the platform? Clearly, the focus today is on MIPLYFFA, is likely the focus tomorrow as well. Just how should we think about the broader strategic vision of the company?
Yeah. So you know over the last 18 plus months, the company has undergone a transformational change, right? We've made a lot, as you mentioned, we've made a lot of very focused decisions that have allowed us to then execute with the infrastructure we've had and to have this success, quite frankly, that we've had. Two things that are important. We're not doing this just because we had one or two assets that we're moving forward. We're doing this because we delivered to the board a strategic plan. And that strategic plan had four pillars that we started to outline at the end of Q3 last year around commercial execution or commercial excellence, we call it, pipeline and innovation, our teams, we have to be able to get our talent and culture right, and then the corporate foundation, as LaDuane mentioned.
Throughout that, we have short, medium, and long-term goals. The short term, this 2025 to 2026 time frame, is about executing what we have in front of us to earn the right to do something else. We also had in there a lot of different scenarios and strategies. A lot of the $217 million that LaDuane talked about gives us 217 million reasons to be able to have more scenarios that we can execute on to see how we might be able to leverage our infrastructure, how we can leverage our development pipeline to see where we can go from there. It starts, everything starts in that short-term window of executing what is here today. It is our commercial launches and it is our late-stage development pipeline. We will earn the right to do something else.
Got it. Maybe we could just talk about a couple of those other assets for a minute. OLPRUVA is your other commercial stage asset that you're commercializing yourself. There's been some headwinds there with that launch. Can you talk a little bit about what you're doing today and what you're doing differently to push that launch forward?
Sure. It started, as you mentioned, we launched, relaunched the program in February, end of February last year. We then came out of the gates with really great engagement with physicians and awareness of the product that had very limited awareness. The pull-through was challenging. We went back to the drawing board and looked at all the feedback we've received. We executed on some work that allowed us to pivot our strategy. We needed to be able to go after where the best clinical differentiation of the product supported the patients. That is in OTC, more female carriers, patients who could actually benefit from the portability of the product, the palatability of the product, as well as the personalized dosing where you could actually differentiate from the competitors that were out there. We kicked that off in Q3.
We've been executing on it now in Q4 early. It's going to take some time to move forward, but we will update next week on our earnings call kind of how that strategy is coming together. I quite frankly think that it's providing us with some learnings that will allow us to continue to deliver on the strategy. It is about making sure that we put the product in the right place to differentiate against the competition and then see if we can get a toehold.
LaDuane mentioned celiprolol in that phase three program. You went through a review of the program and decided to keep investing in the phase three program. Can you tell us why you did that and how you think about the value opportunity for celiprolol ?
Sure. As you mentioned, prior as part of the Acer acquisition that we made about a year and a half ago, we did an analysis of not only the Acer portfolio that we acquired, but also our internal portfolio of a lot of work that has been done over a decade plus that the company had invested in. One of those areas was the vEDS program. It is the Vascular Ehlers-Danlos syndrome program. There are about 7,500 patients in the US.
This was a program that had actually tried to do a paper filing, did not work out so well, but had then the ability to work with the FDA to get a phase 3, single phase 3 under a SPA, decentralized trial, 150 patients, two-to-one randomization that allowed us to be able to continue to invest in that program for a truly unmet need and nothing else in development for those patients. What we believe is a clinically de-risked program because celiprolol is available in Europe and is utilized off-label as a standard of care in certain European countries and has been for some time. Gives us a lot of faith that we can invest in this program, which in a very well-designed trial under a SPA and then try to be able to get this product to patients in the U.S.
It made a lot of sense for us to do it. We then kind of went through the screening patients who had been on the sidelines for some time that wanted to get into trial, but under the previous sponsor were not able to actually enroll because they ran out of funds. We have gone through that now. We have started re-enrollment. We have got patients on board, got the program opened up. Now we have been able to work with centers that have called 3A1 diagnosed patients and make sure that they know that there is a trial available to them to be able to enroll in now. We are starting to see some progression there. We have got to be able to enroll this trial quickly because it is an event-driven trial. As part of our ability to execute and get into product to market means that we've got to get the trial enrolled as fast as possible.
Great. Neil, LaDuane, really appreciate you being with us this morning. Exciting times and looking forward to the earnings update next week.
Thank you.
Thank you.