All right, good afternoon, everyone, and welcome back to day three, our final session from our inaugural Healthcare Innovation Conference. My name is Eddie Hickman. I'm one of the biotech analysts here at Guggenheim. I'm joined this afternoon by Zevra Therapeutics, CEO Neil McFarlane, CFO LaDuane Clifton, and the Chief Commercial Officer Josh Schafer. Gentlemen, thank you for joining me today. Neil, you reported your third quarter earnings last night with some important updates. But before we get into that, could you maybe provide a few-minute overview of the company and sort of what some of your core capabilities are that got you to where you are today?
That's great. Thank you, Eddie, and thanks for having us. I know it's been a long couple of days. As you mentioned, yesterday we just reported earnings, but I'll give you a little bit of an overview of the company. We're a commercial stage rare disease company. We've got two commercial products, two late-stage development programs, and we also get royalties from another program that we out-licensed a number of years ago. If I start with our commercial programs, most recently we got approval of a program called MIPLYFFA, which is indicated for the treatment of Niemann-Pick disease type C. That product was launched in September 20th when we got our approval. Josh will talk a little bit more about that later on.
We have another commercial product that was an acquisition we made last year from a company called Acer Therapeutics that is for UCDs, urea cycle disorders and certain urea cycle disorders, and that product's name is OLPRUVA. That's been in the market since we launched it at the end of January, and taking that learnings into our MIPLYFFA launch. We have two late-stage development programs as well. One of those programs is KP1077, which is a serdexmethylphenidate. It's a proprietary pro drug that we developed internally. It's one of the key ingredients that is in the product called AZSTARYS that we out-licensed to Corium for ADHD, and that program is in development today for idiopathic hypersomnia. We had our end of phase two meeting here last quarter, have a pathway for a pivotal phase three trial.
I can talk a little bit more about that later on, but we're excited about the opportunity to be able to get that product to market. And we have our last program in development is a program called celiprolol for another ultra rare disorder called vascular Ehlers-Danlos syndrome. That's a rare connective tissue disorder that leads to ruptures of mid-sized vessels and/or hollow organs. And we're in phase three in that program, and we restarted that phase three program enrolling after our acquisition last year of Acer Therapeutics in Q2 and got our first patients dosed in Q3. So, as I mentioned, we have royalties and milestones that we received from the out-license of our development program called Serdexmethylphenidate, and that's in a program called AZSTARYS for ADHD today.
So we're a small company, a busy company that's come together in a short period of time and executing one of these things at a time that's led us to today.
Yeah, I know lots going on, and I think, you know, we'll start with MIPLYFFA, of course, you know, getting that over the finish line and the approval. Maybe, Josh, before we talk about sort of some of the early launch metrics, can you just talk about some of the challenges of launching a new drug in this sort of ultra rare disease space that's unique and sort of what some of the capabilities you've brought forward with your commercial team to sort of get to sort of launch this drug strongly, you know, next year?
Yeah, so in any rare disease launch, it really is about two things. It's one, being able to identify these patients. By definition, it's a small patient population in any rare disease, being able to clearly identify who is it that's going to benefit from the treatment, and then ensuring that a company has the capabilities and the resources to pull those patients through from sales, medical liaisons, and importantly, patient services. And in rare diseases, it's not just about writing the prescription. It's about helping patients sort of through the entire reimbursement journey and making sure that they can get appropriate access to those therapies. And in that context, we've put in place a commercial team that does all of those things. And it was really started in January when we launched OLPRUVA for urea cycle disorders.
And that gave us the opportunity to build from scratch a new commercial team that got out in the field, engaging with metabolic specialists and geneticists who treat UCD, but also do the initial diagnosis for Niemann-Pick. So we were really pleased with the capabilities that we've been able to build over the course of the year.
So you have an ongoing EAP in the United States, you know, following the approval, and it sounds like that's one of the most important groups of patients that you're focusing on right now. Can you talk about where those patients came from, sort of what you've already seen, you know, efficacy-wise in those patients, and then sort of what your strategy is to sort of get them converted to paid drug?
Yeah. So just to make sure that we're clear, the EAP patients are certainly important to us, but not the most important. All patients are important to us. What was really important is that we have this ongoing expanded access program that had 83 patients in that program, and these are patients who are receiving for, in some cases, years the benefit of MIPLYFFA and miglustat. And so we wanted to make sure that we were allowing for those patients to continue on MIPLYFFA after it was approved and be able to transition them from clinical drug to commercial drug, so that certainly was a priority. But at the same time, we were ensuring that patients who had not been exposed to MIPLYFFA were still able to enroll into the program and have prescription enrollment forms coming through.
And you say you have patients that are sort of de novo enrolling in the EAP now. Is that continuing, or is that now stopped that you have commercial drug?
Again, another clarification. We have an enrollment program, which is basically the submission of a prescription to our specialty pharmacy. We announced yesterday that we have 90 enrollments. Of those 90, 69 of them came from patients who are currently on MIPLYFFA through the expanded access program. The remainder of those 21 were patients who had not been exposed to MIPLYFFA previously.
Gotcha. So the, yeah.
Eddie, if I could just add a little bit to that, you know, we had been saying for many months and leading up to our advisory committee, we had approximately 70 patients in our expanded access program. At the time of approval, that number had grown after our AdCom, and we had a number of patients and physicians trying to get patients enrolled in our expanded access program. That number grew to about 83. Just to clarify something that you said earlier on, we are no longer enrolling patients into the expanded access program. So that 83 number was the final number. We now are moving forward with the commercial launch and execution.
Great. No, that's helpful context. Your label maybe was unique to some in that it sort of clarifies co-administration with miglustat, which is not approved to treat NPC in the United States. How many patients do you expect are on miglustat currently, and do you think that will change at all given that it's sort of required to be on MIPLYFFA?
Just kind of full context, there are 900 patients in the U.S. that it's estimated have NPC, of which about a third, roughly 300-350, are diagnosed and receiving some sort of treatment. The majority of those patients are receiving miglustat. That's considered kind of routine care, even though it isn't approved, but that's what most patients are on. And we know from literature and from our own research that about 80%-85% of those patients are on miglustat. And the remainder are not on it either because of reimbursement challenges or intolerability due to some side effects. So this indication in combination, we think, is actually a real benefit to patients because it allows them to get the benefit of both MIPLYFFA and miglustat together.
We can't really speak to how many additional patients are going to be on miglustat as a result of that, but we certainly don't see it as any limitation to either.
So you noted 300-350 sort of patients that are being diagnosed and treated. Do you know where those patients are and sort of are they sort of concentrated around certain centers of excellence and sort of how many do you have to go out to the community and find?
Yeah, we do have a pretty good sense of where most of those patients are. These patients are diagnosed definitively through a genetic test and through conversations and diagnoses from specialists who are in centers of excellence, and there are about 30 or 40 of those centers of excellence across the country. That's where they'll go for their initial diagnosis, initial treatments, and then go back to their perhaps a pediatric neurologist and they're closer to home that is more community-based. But we know where those prescribers and those patients who are currently diagnosed are.
And then what sort of work then has to be done to sort of find and target those other sort of 500-600 patients that you think are out there based on the prevalence numbers?
It's going to be a variety of a bunch of different things. One, we know from all of our collective experience that when there is a new treatment available for a disease that previously had no treatment, patients present more frequently as the awareness of the need to treat and treatment options become available, but we're also being very proactive in making sure that our data are published and that there's awareness of the disease and so that we've got a very robust publication and communication plan. We're attending conferences. In fact, our team is at a pediatric neurology conference this week presenting some data from our pivotal trial, and then there are other tactics as well that we're doing, such as partnering with some states to try and ensure that NPC testing is on the newborn screening at some point in the future.
Hopefully that'll happen soon, but that's on a state-by-state basis, and then other tactics to look at claims data to be able to identify patients who have perhaps frequently misdiagnosed comorbidities, things like that.
Yeah. So this is a weight-based drug. Do you have a sense of sort of what the average weight is of, and I guess then sort of price for the current patients and maybe how you think that might evolve as you sort of further penetrate the known patients?
Yeah. If we were to just take the average sort of weighted average weight of the patient in our Expanded Access Program, it really skews towards the higher of the two out of our four doses. And the price for that is roughly $1 million a year.
Great. I guess a lot of these patients are pretty severely disabled or have significant comorbidities. How should we think about maybe discontinuation rate in the real world versus what was seen in the clinical trials? And do you have sort of any insight on how that's evolved in the sort of ongoing EAP as well since those pivotal trials read out?
Yeah, so it's important to keep in mind that many of these patients are under the care of a parent or another caregiver, and consequently, the compliance and persistency in these patients is much higher than you would see in other situations. Using our, again, our expanded access and long-term open label study as a gauge, these patients were very persistent and stayed on for, in some cases, up to five, six, seven years, and we would expect that to continue.
And what are the sort of key reasons for discontinuation? And like, I guess if it's tolerability, what is that? And can that be managed sort of with extra education or titration or things like that that can help?
The MIPLYFFA actually was seen to be very well tolerated. Most of the discontinuations, unfortunately, were to patients dropping out either due to death or just getting to the point where a therapeutic intervention was no longer viable for them.
So you mentioned some of the metrics that you have in terms of getting these EAP patients converted and some of the non-EAP patients on drug as well, but it's going to take some time to get the drug into the channel. Can you sort of explain how patients get drug and sort of what the cadence of how you book revenue and how we should expect sort of the yearly revenue to look based on when patients may first get access to the drug?
Yeah. So we record revenue when it ships to our specialty pharmacy. So I think as you start out with this process, we're excited about the current rate of enrollments, and that'll inform an initial order. And then as we go into next year, as you see that, I guess the prescription cadence start to get more normalized, then we'll continue to see how those shipments go through.
Gotcha. And the specialty pharmacies are sort of controlling their ordering based on what they're seeing and sort of the cadence of scripts coming in?
Yeah, exactly. They get their part and parcel of that enrollment process, and the whole patient services hub is kind of built around that with them in the middle. So they have visibility into what's coming and how to plan.
Is it one specialty pharmacy or like can you talk have they sort of disclosed sort of how sort of if they want to have a certain amount of time in channel that they're comfortable with, or is that going to evolve as the launch continues?
So it is one specialty pharmacy, it's Orsini. We announced that previously, that it's not an exclusive relationship, but it is just the one SP that we have. And no, we haven't disclosed how much of a safety stock or how much inventory we would have. And we'll just kind of continue to monitor that as we see the enrollments come in.
You know, you mentioned that you've gotten a good number of patients on sort of approved paid drug. What have been the challenges so far in getting the rest of them converted? And have there been denials? And what have those reasons been? And sort of what work have you done to sort of try to mitigate those denials?
Yeah. So just to kind of walk you through the process and how this works. An enrollment, again, is a form that is basically a prescription form sent to the specialty pharmacy. And that initiates an investigation of the benefits. We've had 90 of those enrollments come in, and we are continuing to work through all 90 of those. What we announced the other day, yesterday, was that 30% of them, or roughly 27, 30, have already been authorized. The others are somewhere in the process, and we're still in the midst of negotiating. And we go through the same process any rare disease would, where in some cases, plans might approve it immediately. In other cases, they might need a letter of medical necessity or a conversation with the clinician. And we're in the midst of kind of working through all of the 90 of those at this point.
The last point I'll make on that is this is a prescribing community that is very accustomed to this type of reimbursement and the need to engage with payers. And they're highly motivated to ensure that their patients get MIPLYFFA. And so there hasn't been any hesitation to engage in those peer-to-peer conversations or write the letters of medical necessity.
Right. And it sounds like you're, go ahead.
I was going to say, Eddie, maybe I'll add one additional logistical item here. Remember that Josh mentioned 80%-85% of the patients that are out there today who have been treated, they're being treated with miglustat. And that's an off-label drug that now we have a label for that states MIPLYFFA in combination with miglustat. So they've been able to already get the approval, potentially 80% of those patients that are out there for an off-label product that now you actually have data in the label that states, here's what the product, here's what your patients do in our clinical trial through 12 months with miglustat. And then here's what happens when you add miglustat and MIPLYFFA together. The robustness of the two-point change in our NPC CSS, or the rescored four-domain NPC CSS to be exact, halts the progression of the disease.
When you think about a patient that's out there today, they're already on a product that is part of the labeled product that we then bring the additional product to. You have this differential in data where you see this two-point change in progression. It's a pretty strong case that's being made through the payers at this point.
You mentioned, I think on the call yesterday, that you expect 80% of covered lives in a year. Is that what you said? 60% in six months, 80% in a year?
I don't recall stating that. I think what the 80% was the percent of NPC diagnosed patients who are on miglustat.
Okay. So I guess I was going to ask about the sort of level of commercial coverage and then how it may have, how Medicaid or sort of non-commercial coverage, how you expect those to evolve over time?
I think it's too early to tell. I mean, of the paid authorizations that we have now, it is from both commercial payers and federal, primarily Medicaid patients. So it's too early to kind of be able to speculate on that. What we did announce yesterday, which I think is an important one, we wanted to get out our October, put a line in the sand. October 31st, here's what we saw in patient enrollments. Here's what we've seen so far in benefits investigations that have been approved for payment. We also announced though, what are the metrics that we're going to be providing to the Street in the future, and that's going to be patient enrollment forms. That's going to be what does our covered lives look like as we get into our launch.
We'll have a little bit more understanding a few weeks or a month into the launch. It's a little too early for that. And then I think very importantly, we're also going to be able to announce revenue on a quarterly basis to the SP. So this will be able to provide what's happening on the top of the funnel and then what's coming out on the bottom as well.
So Neil, that was two weeks ago. Anything you can sort of tell us anecdotally about what you're seeing in the last two weeks beyond what you reported sort of?
Yesterday?
Yesterday.
No. I can't, but what I can do is I can give you a good sense that there are more prescription forms that have come in, and we are actually continuing down, and this is a really important point. We are continuing down the benefits investigation process and seeing more patients get approved, so this launch, and we said it yesterday, has exceeded every expectation for us. We think it's a very exciting testament to the community at this point as well in regards to the work that they've done to the groundswell of getting MIPLYFFA and supporting us in our approval, and now it's our turn to give back.
You're very confident in how the early launch is going that you sort of moved up guidance for closing the EAP by about six months. Sort of what gives you that confidence that over the next six months you can do that? And then sort of what does the second half of next year look like when you start to have to penetrate sort of non-EAP patients out in the community?
Yeah. Great time for us to be able to change that guidance because we've exceeded our own internal expectations. 69 of 83 patients' enrollment forms have already been submitted. That's well ahead of where we thought we could be. That's why we believe that we can get to the end of the EAP by the end of Q2. Additionally, as these patients get through their EAP, there's final visits, there's end of the study questionnaires, and the fact that we've got 21 patients that are outside of our EAP today that have never been on MIPLYFFA, that have already put prescription forms, and then some of them have also gotten the benefits investigation approved, it gives us some pretty good line of sight that we can get those remaining from 69 to 83 patients through the process.
And I think this is an aggressive timeline that we put forth because normally you would see about a year timeframe to get these patients through an EAP and then into commercial product and out of your EAP trials. This is a true testament to the work that the team has done and the community is doing as well to support that transition.
Yeah. It's really impressive timelines. Before we, in the last few minutes, talk about a couple of other opportunities, anything else you want to say on the MIPLYFFA U.S. launch that we didn't talk about or think that's worth bringing up?
No. Thankful.
So Europe, what's the strategy there and what are the timelines for when we could have approval there?
Yeah. We've been talking about the fact that we're really focused on the U.S. approval. And the reality is that a lot of the questions that came in our CRL were very similar to those questions that were posed in the European filing. And that allowed us now to take this robust package, repurpose it to be able to get back to Europe to answer those questions. It's early for me to tell you what the timeline looks like, but it is a priority project for us internally to be able to reengage and understand what our best path forward is for those patients in Europe. Reminder, we have about 70 to 80 patients, additional patients in our European EAP, of which about 30 of those patients are based in our French national ATU program.
We want to make sure that, and they have all been very consistent and stable as well. We want to make sure that we get this product in the hands of those patients as soon as possible. In the first half of next year, we're going to have better guidance for the Street and everybody on our European filing strategy.
But you don't think there'll be another study that Europe requires? You think you'll be able to apply with what the data you have? Or do you think there's a possibility that you could have to run another study?
Our first attempt is to be able to answer the questions that were out there, which is what we did over the last few years in doing the natural history work, doing the longer-term data. We're going to try and utilize what we have first.
Great. You also have, I guess if you want to mention sort of like your cash guidance right now, but you've also mentioned that it doesn't include this PRV that you have. And we've seen them sort of go sort of beyond $100 million now recently, up to $150 million. Can you talk about what your plan would be for that cash and sort of the timing of when we might see that influx?
We just reported yesterday that we ended Q3 with $95.5 million in cash on the balance sheet. We continue to be in a very solid position as we go in to support this launch as well as going into 2025. As you pointed out, Eddie, we did receive the PRV as part of the approval of MIPLYFFA. That's been an interesting market to watch how it's developed. You may remember in early August, we did an offering, a small offering just after the adcom, but before approval that really added some cash to the balance sheet and gave us additional flexibility to really sit back and watch the market and make sure we think about the PRV in the right way.
So a few recent comparators in terms of PRVs that have been sold recently kind of suggest maybe the market is increasing and we're encouraged by that. But we're going to continue to be disciplined about when and at what level we're willing to sell the PRV. So stay tuned, but we're watching it carefully.
Just last thing, is this a market where increasing the sales force substantially can accelerate or help the launch? Or is it such a rare launch where you sort of maximize your touch points at this point?
Yeah. No, we optimized our commercial infrastructure, our medical infrastructure when we launched OLPRUVA. So what you see here today is a sales force, is a medical group that can actually execute on both of these launches and drive value. And that's a testament to the 90 patients that have already got prescription forms in.
Great. I think that's all the time we have. I appreciate you guys joining us. And we'll look forward to how the launch goes. Thank you.
Thanks for having us.
Yeah.