She still remembers it.
Okay, we're going to get started. David Amsellem from the Piper Sandler biopharma team, and we're delighted to have the team from Zevra Therapeutics join us for the 36th Annual Piper Sandler Healthcare Conference. So thanks, gentlemen, for joining us. And let's, Neil, I'll start with sort of a big picture question. I like starting off with big picture questions. So you gained approval of Miplyffa for Niemann-Pick type C recently. You launched it. You have Olpruva for urea cycle disorders. So your commercial portfolio is really coming into focus. So you have that, then there's pipeline. And beyond that, you've talked of ways to leverage your commercial infrastructure. So there's a lot of different moving parts when it comes to all things Zevra. So I guess the question here is, what is the big priority or how are you balancing all these different priorities?
Yeah, thanks for having us, and I appreciate the invitation. I should also start by saying I may be having some forward-looking statements. So take a look at our most recent SEC filings for the most up-to-date information. And to answer your question, David, is focus. We are an organization that, as you mentioned, has a number of various value-creating opportunities. And what we have done over the last 12 months is really started to focus our efforts into those things that can drive value for patients and drive value for investors. Our goals today are to execute on two of those that you talked about right now, which is the launch of Miplyffa and the launch of Olpruva. Those two are ongoing, and we'll get into those in a little bit later. But that is a core focus of our efforts right now.
Along those lines, our next goal is to be able to move forward with the MAA application of Miplyffa in Europe. That is a priority for us to be able to know that what we've done with the FDA and the additional data to get that product approved in the US, we now need to get to Europe, to patients that are there. In terms of our pipeline, we made some interesting comments in our last call, what we've been told is interesting comments in our last call. But I think to make it clear, we've done a lot of analysis over the last 12 months on our pipeline around our sleep asset and our 1077 program, as well as in our celiprolol program for vEDS. We'll talk about those a little bit more later.
But part of that analysis, we made the determination to explore strategic alternatives after a very successful end of Phase 2 meeting and a clear pathway for a single pivotal trial in IH to actually look for strategic partners and alternatives because of the fact that we want to be able to focus our efforts in the rare and ultra-rare area and leverage the infrastructure we have. So it's about focus, and we think that the actions we're taking are starting to drive the reality that we are focusing this organization on what can drive value.
Okay, so let's talk about Miplyffa and Niemann-Pick. And I'll just ask a general question, just how you're sizing up the opportunity, particularly given that your approval came around the same timeframe as another approval that's IntraBio's Aqneursa. So how do we think about the opportunity for your product in the context of this other product also being approved?
I think the physician community and the patient community has made it really clear prior to the approval of Miplyffa and the additional products that this is a heterogeneous disease. It takes multi-drug approaches to be able to truly impact the lives of these patients with this devastating neurodegenerative disorder. For us, and now with our launch metrics that we talked about at the end of October, we've seen a tremendous uptake of the product in the first five weeks post-launch with 90 prescription forms that have come in. Physicians have continued to tell us that Miplyffa, in combination with Migalastat, and the strength of the data that we have will be the cornerstone of therapy. And additional products have come to market that are symptom control and/or patients who have epilepsy, they have also anti-epileptics that come on board. You've got ataxia.
There's a drug now available for you there too. They've made it pretty clear that there's a disease modification that you've seen in the data with our label. That's where you're going to start, and then you're going to add on where necessary. I think that's fairly standard in a lot of heterogeneous type rare disorders that display themselves in various ways.
Yeah. How do you think about, or how should we think about the differences between Miplyffa and Aqneursa in NPC? I mean, I guess in terms of your messaging to physicians, how do you, I know there's heterogeneity, but just in terms of the key differences, how are you positioning it to physicians?
I think it goes back to being a multi-drug approach to therapy. We have data that is in our label that says Miplyffa, in combination with Miglustat, halts the progression of this disease through 12 months through the only validated scale in terms of the Niemann-Pick C severity scale. And we went through quite the unveiling and through our advisory committee around the level of data and the amount of importance around swallow, importance around the other areas when it comes to the Niemann-Pick C Severity Scale, that halting the progression of this disease, which is what we see versus Miglustat alone, is really what the cornerstone of therapy and patients have been looking for. Additional products have come to market that have, for instance, ataxia. I think it's great that those products have the ability to treat those areas like ataxia.
But there's a differentiation when it comes to disease modification versus symptom control.
So you mentioned, yeah, go ahead.
I was just going to add as well, one of the other key differentiators is that through the breadth of the studies that we've had for Miplyffa, we've treated over 270 patients with NPC, which really demonstrates both the clinical benefit but the safety as well. And in our label, we have some patients who have been on therapy and received benefit for up to five years. That speaks to the long-term benefit that is really unique to Miplyffa.
So you mentioned Miglustat. This is sort of more of a reference question, but just remind us what portion of the NPC population is actually on Miglustat since you are indicated in combination with Miglustat?
Yeah. Through our studies and through publications, you see about 80%-85% of patients on Miglustat that are treated, which is what we saw in our clinical trial, which is what pretty much everybody's seen in their clinical trials as well.
Got it. So you did provide recently on your third quarter call some early commercial metrics surrounding Miplyffa. Can you just talk to prescription enrollment trends and also what the reimbursement landscape looks like?
Sure, so on our quarterly call, we provided data through October 31st, and at that point, we had been receiving enrollments for the better part of a month, and we shared that we had 90 prescription enrollments at that time, of which 69 had come from our expanded access program, so that, I think, really demonstrates the demand. We also announced at that time that we had, I think, 29 paid authorizations, speaking to the fact that as enrollments come in, we then go through the benefits investigation efforts, and we've gotten that many approved at that point. That number continues to increase as we work through those enrollments.
Okay, and just remind us, how many patients are in the expanded access program?
So we previously announced that there were 70. But after our AdCom, there was a lot of interest in getting into that study. And so at the time of approval, we had 83 patients in our expanded access.
Okay. And what is the lag time these days between, and I know it's early days, but I still got to ask the question. What's the lag time between enrollment and fulfillment? And what do you expect that to be like steady state?
So it's early days to give you a number on that. And I would also say that it really varies based on a payer, whether it's a Medicaid patient or commercial, and then there's variability within the commercial. So I can't give you an answer on that. Hopefully, this time next year, we'll have a little bit more context to be able to provide, but it's varied. But I will say that our team is doing a great job of working through every single patient that's coming in through the enrollment.
Yeah, maybe I'll add a couple of things. We talked about an additional metric, and a few weeks ago, we announced that we also got drug in channel within the 8- to 12-week guidance that we put out. We came in on the early part of that guidance. This 30% of the 90 patients that have had prescription enrollment forms that were approved, those patients are now shipping. But we've had additional patients that have come in through enrollments. We've had additional payer coverages that have now been approved through the process. So we utilized that October 31st kind of time point to show the progress of the early stages of the launch, which exceeded every expectation and every metric we had in our organization.
I think now that we've been able to get drug in channel, that drug now is starting to ship to patients on a regular basis, a daily basis, actually. We're working through the kind of bulge in the snake, if you will, right now. The team has done a wonderful job. The patient services group is doing a great job and having the conversations ahead of time. We're in a position now where we feel that a lot of the heavy lifting we did from the launch of Olpruva, a lot of the learnings we took to get the right specialty pharmacy, a lot of those pre-launch planning activities that took place with payers and physicians and patient advocacy organizations are now all coming together and kind of the perfect storm. Can you remind us what is the mix between commercial and Medicaid patients?
Yeah, it is slightly more than 50% commercial. The remainder are largely Medicaid and then some Medicare patients. So this is a really heterogeneous in terms of age of onset. But most of these patients are commercial.
Okay. So you mentioned Europe and filing there. Help us understand the opportunity in Europe. Is this something you're looking to do on your own or look for a partner? And then I have the standard question on what do you think price will look like relative to the US? So just help us frame the opportunity over in Europe.
Let me see what I can do to provide some insights to those questions. Importantly, the product was originally filed in Europe back in 2019 before the filing was then taken off, but we continued to move forward. A lot of the same issues that we got the U.S. complete response letter on were the same issues that Europe had. So we were able to actually take and focus our efforts into the FDA filing, get an AdCom, get the robustness of the package to address the unanswered questions in the CRL, which were primarily the same questions in Europe. So our goal now is to be able to take this robust package that we've gotten through the FDA, reestablish and reengage with Europe.
I cannot give you a timeline yet as to the MAA because we're deeply in the strategic process with a couple of advisors to help us understand how fast we can get the product to market in Europe fastest, and while we work through the regulatory strategy on how to move that forward, Josh and the team have been doing a great job of understanding what would it take for a single product in Europe to actually provide a return on investment, and I think that the goal here for us today is focus on how fast we can get it to market while we do that assessment, and then we'll come back to you and to others and let everybody know what our decision is. The last one you talked about in terms of pricing and the market.
In Europe, there are about 1,100 patients from a prevalence perspective with NPC. There is an approved product in Miglustat in Europe. It's been around well over 10 years, and the marketplace is a little bit more mature. So the 300-350 patients in the U.S. of those 900 patients that are from a prevalent perspective, we're not as far along in the U.S. So in Europe, more established market product that's approved, a lot more patients that are being treated today. We have 70-80 patients in Europe in our expanded access program today. Our goal is to get it to market as fast as we can, servicing those patients and the broader market potential.
Okay. Let's switch gears. Actually, before we do that, I did want to ask you about how we should think about exclusivity and IP runway for Miplyffa. Yeah, let's do that. Yeah.
Today, we have been communicating that Orphan drug exclusivity up to seven years is the runway that we have. As you know, when you work through these CRLs and you have these delays, there are opportunities for patent term extensions. That is a process that we're undergoing, but I can't tell you what that is until it's final.
Yeah. Is there anything patentable that we should be thinking about regarding arimoclomol?
We've put forth some provisionals throughout prior to our AdCom and others that we're prosecuting. Our goal right now is to communicate orphan drug exclusivity and the upside potential when we have more concrete information on timelines outside of that.
Got it. And then switching gears, the Priority Review Voucher, you had received that with the approval. Any recent thoughts on your efforts to monetize it?
Yeah. On our Q3 call, we actually mentioned that it is our goal to monetize that to help provide non-dilutive capital, help support our programs moving forward, and grow our next phase of growth. The market has been dynamic. There have been a number of prints that have been significantly higher than the previous decade over the last six to eight weeks, and we think that there's an opportunity for us to be able to execute on a PRV and, again, provide that non-dilutive capital on the balance sheet.
Okay. So I want to spend time talking about Olpruva and urea cycle disorders. So there's other modalities here, other products. There's Buphenyl and there's Ravicti. And so I wanted to spend some time talking through how you think about differentiation for Olpruva relative to those two products.
Yeah. Josh?
Yeah. Thanks for the question. So it's important to keep in mind that most of the products that are used right now for the treatment of UCD are all some sort of nitrogen scavenger, but much the same active ingredient. So the differentiation is really kind of on the secondary level, which is around convenience to the patients, the ability to mask some of the taste issues and palatability issues that exist with current therapies, and Olpruva, it was designed to do all of those, which was to be portable, and it comes in a pouch that makes it easy for a more independent and active patient to carry the drug with them. It is palatable and has been designed and reformulated to mask some of those issues, and it's personalized in dose, so there's no need to titrate the dose.
And for many patients, that is really appealing, particularly patients who are kind of moving from adolescence to young adulthood and trying to establish more independence. A newly sort of identified patient population is the female carriers who might not yet have symptoms but have children who have UCD. And so these patients have gone and been tested, and these are great candidates for Olpruva.
Can you talk to the challenges associated with uptake, just considering that Buphenyl is available as a generic?
Yeah. So just to be candid, and we mentioned this in our earnings call, the launch has not met our expectations, and we're continuing to work to refine the strategy and to really understand the market dynamics. I think one of the major issues is that it is a well-established market, and patients who have been on current therapies typically get a 12-month prescription and authorization for up to 12 months. So trying to switch those patients mid-year has been challenging. We've really focused on building awareness for Olpruva as a great alternative for patients. Now, as we're coming to the end of the year, as patients are now looking to have their prescriptions reauthorized, we're finding that many of the current therapies are on exclusion lists. Olpruva is a great alternative for those patients.
We're seeing more and more patients expressing interest in talking to their physicians about moving to Olpruva. We really hope to see that shift in the first quarter.
Okay. And how are you thinking about the landscape going forward? My understanding is that a generic of Ravicti is going into the market in the not-too-distant future. What does that mean for uptake and reimbursement?
Yeah. We're aware of that. There are a couple of authorized generics for Ravicti, which is important because it'll be very similar in terms of the active ingredient and the way in which Ravicti is delivered. We think that the benefits of Olpruva will still be able to outweigh any authorized generic for Ravicti. And so that is weighing into the shift in our strategy to a specific patient segment and also really focusing on payer pool.
Yeah, and in terms of segments, I mean, can you talk through which patients or which groups of patients you think are the most appropriate or maybe the lowest-hanging fruit, if you will? I mean, you mentioned this is more or less an established market, but are there, quote, low-hanging fruit here?
I don't know that there are any low-hanging fruit, but Olpruva certainly provides meaningful benefit to a certain segment of the patient population. And again, it's those who are looking for greater independence from their therapy, who are looking for the ability to have portability with the envelope, personalized dosing, so it's easier for them to take and administer. And we think that that patient population is pretty meaningful. In fact, our team has been out talking to clinicians who have sort of self-identified a number of patients in the hundreds who they think would really benefit from Olpruva.
Okay. So you have infrastructure, commercial infrastructure that you've put in place. Can you talk to the ways in which Miplyffa synergizes with Olpruva in terms of your commercial infrastructure and this rare disease model? And what are the implications for spend as we.