Good morning, everyone. Thank you for joining Zevra Therapeutics conference call, focused on the FDA's approval of MIPLYFFA. After prepared remarks from Zevra's leadership, we will open the call to questions. Please note that today's call is being recorded, and a replay will be available via the Events and Presentation section of the company's website. I will now turn the call over to Nichol Ochsner , Zevra's Vice President of Investor Relations and Corporate Communications.
Good morning, and thank you for joining us on today's call to discuss the FDA's approval of MIPLYFFA. I encourage you to access our news release that was issued on Friday, September 20th, and it is available in the investor section of the Zevra Therapeutics website. Today's call will include forward-looking statements. These forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties, and other significant factors that may lead to actual results differing materially from the projections made.
Please refer to the Risk Factors section in our most recent quarterly report on Form 10-Q and our other filings with the SEC, including our annual report on Form 10-K. The speakers on today's call are Neil McFarlane, Zevra's President and Chief Executive Officer. Adrian Quartel, our Chief Medical Officer. And Josh Schafer, our Chief Commercial Officer and EVP of Business Development. Also, for the question and answer session, LaDuane Clifton, our Chief Financial Officer. I will now turn the call over to Neil.
Thank you, Nichol, and thanks to everyone for participating in this call. Last Friday was a day of monumental importance to those living with Niemann-Pick disease type C, or NPC, along with their family members, patient advocacy groups, and clinicians. It also marked an extraordinary milestone on our journey to become a leading rare disease company. Together with the NPC community, we at Zevra Therapeutics look forward to changing the treatment landscape for this devastating disease.
As we announced, MIPLYFFA, which is the brand name for arimoclomol, is now approved and indicated for use in combination with miglustat for the treatment of neurological manifestations of NPC in adult and pediatric patients two years of age and older. From our extensive work with the medical, payer, and patient communities, we're pleased with MIPLYFFA's label. The indication and strength of the data in the label highlight the opportunity to slow progression of disease.
While subjects treated with miglustat alone in our pivotal study progressed approximately two points over twelve months, we saw that decreased progression was halted. Sorry. We saw the disease progression was halted for those treated with MIPLYFFA and miglustat in combination over the same period of time, based on the rescored 4-Domain NPC Clinical Severity Scale. The opportunity to delay or prevent two points of progression and preserve essential functions in ambulation, fine motor skills, speech, and swallow is a great benefit for people living with NPC. Importantly, these impressive data support our belief that MIPLYFFA will become the cornerstone of therapy. Given that approximately 80% of people diagnosed with NPC are treated concomitantly with miglustat, we anticipate the labeled indication supporting the combination use with MIPLYFFA will help to remove historical access barriers to receiving treatment.
We are also pleased to report that with the approval of MIPLYFFA, Zevra has received a rare pediatric disease priority review voucher, which is a valuable asset that can be monetized to fuel our company's next phase of growth. Lastly, as noted in our news release, we have launched a comprehensive support program for caregivers and people living with NPC who take MIPLYFFA. The program, AmplifyAssist, will be an integral part of our mission to help provide access for all eligible individuals. We are grateful for the unwavering support of the community that stood with us throughout this journey. The strength and commitment of people living with NPC, their families, the advocacy groups, along with the researchers and clinicians who collaborated with us every step, cannot be overstated.
To the remarkable team at Zevra Therapeutics, past and present, thank you for your focus and relentless pursuit of approval of this much-needed treatment. Without your dedication to our mission, today's achievement would not be possible. At this time, Adrian will provide clinical information about NPC and review the MIPLYFFA prescribing information. After this, Josh will share details about our product launch activities and AmplifyAssist before we begin the question and answer session. Adrian?
Thank you, Neil. Today marks the achievement of a hope and dream for many families and their loved ones who suffer from NPC. For decades, families in the U.S. have faced the frustrating and daunting reality of managing the debilitating neurological symptoms of NPC without an approved treatment. With this reality as a motivation, we pursued the approval of MIPLYFFA as a new treatment option. In fact, as highlighted at the Genetic Metabolic Diseases Advisory Committee meeting in August, we are here today because of the courageous people living with NPC, such as Alec, who was diagnosed with NPC in 2012 at the age of fourteen. With strength and hope, Alec has spent the last decade participating in community sessions and striving to be an advocate, not only for himself, but for all those impacted by the disease.
Alec's journey is intertwined with that of his sister, Haley, who passed away from NPC at 20 years of age. Although Haley is no longer with us, her memory continues through the family's ambassadorship to the global NPC community. Unfortunately, this situation is too familiar for many people living with NPC and their families. However, with the approval of MIPLYFFA, physicians have, for the first time, an FDA-approved medicine for use in their unwavering battle with the disease. I'm incredibly proud of what we have accomplished as a mission-driven, patient-focused company. Before discussing the FDA-approved label for MIPLYFFA, I would like to briefly discuss NPC, the disease for which MIPLYFFA is indicated.
Niemann-Pick disease type C is an ultra-rare, progressive, and neurodegenerative lysosomal storage disorder, characterized by an inability of the body to transport cholesterol and other lipids within the cell, leading to an accumulation of these substances in various cell types, including neurons. The disease is caused by mutations in the NPC 1 and NPC 2 genes, which are responsible for making NPC 1 and NPC 2 lysosomal proteins. Both children and adults can be affected by NPC, with varying clinical presentations. Those living with NPC can lose independence due to physical and cognitive limitations, with key neurological impairments presenting in speech, cognition, swallowing, ambulation, and fine motor skills. Disease diagnosis can often take years, with disease progression being irreversible and commonly leading to early mortality.
With this as background, I would like to discuss the label for MIPLYFFA, which the agency approved as an orally delivered treatment for NPC, in combination with miglustat for adult and pediatric patients two years of age and older. MIPLYFFA has convenient dosing or flexible administration options and can be taken at home. One capsule is taken three times per day, with or without food, and can be mixed with water, food, or administered via a feeding tube. The approval was based on the totality of data in the new drug application that included additional evidence supporting trial endpoints, FDA-preferred analyses, and additional clinical and non-clinical confirmatory evidence. Additional confirmatory evidence included data from a 48 month open-label extension study that suggested improved outcomes when compared to a matched NIH natural history cohort.
Details and analysis of the pivotal study were presented at the 2024 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism earlier this month. Specifically, MIPLYFFA, in combination with miglustat, halted disease progression through 12 months with a decrease of 0.2 points, while trial subjects treated with miglustat alone experienced a 1.9-point progression of the score for the 4-Domain NPC Clinical Severity Scale, leading to a 2.1-point difference for those patients treated with MIPLYFFA. To put this in perspective, it is important to understand that a one-point change in the 4-Domain NPC Clinical Severity Scale can represent a meaningful difference in a person's functions, including, for instance, the difference between an individual being able to eat independently versus needing a caregiver to feed him or her.
The difference between an individual having difficulty swallowing during eating some of the time versus all of the time, or the difference between needing a wheelchair and being able to walk on one's own. Moving to the safety summary, the warning and precautions in the label are consistent with what we saw in the pivotal study, where the most common serious adverse reactions reported were hypersensitivity reactions such as urticaria and angioedema. The most common side effects of MIPLYFFA included upper respiratory tract infection, diarrhea, and decreased weight. Overall, we are delighted with the MIPLYFFA label and excited to bring the first-ever FDA-approved treatment for NPC to those in need. Given the complexity of disease, we recognize, along with treating physician, the need for multiple treatment options in NPC.
The strength of these data and the opportunity to substantially delay disease progression will help establish MIPLYFFA as the cornerstone of treatment in NPC management. This accomplishment would not have been possible without the tireless efforts of the NPC community, the patient advocacy groups, researchers, the clinicians who understand the needs of this community, and our committed and diligent team at Zevra. I will now hand the call over to Josh. Josh?
Thank you, Adrian. Our team couldn't be more excited and honored to support the NPC community by ensuring MIPLYFFA is as widely available as possible. We've been actively preparing for the launch, and our team has been in the field engaging with clinicians, payers, and patient advocacy groups. Our launch infrastructure was built to reach as many people living with NPC as possible by leveraging the strategic fit and the synergies that exist between MIPLYFFA and OLPRUVA, our other marketed product for the treatment of various urea cycle disorders. Both products address genetic metabolic diseases treated by a multidisciplinary team, co-located within the same medical centers of excellence. This enables us to reach the majority of prescribers with our targeted rare disease team.
Awareness of MIPLYFFA is already high in the NPC community, and this concentration of overlapping prescribers has helped our team to build anticipation for the launch of MIPLYFFA. With payers, our priority is to rapidly establish broad coverage for people living with NPC, consistent with our label. We estimate that the payer mix is approximately 55% commercial and 45% Medicaid and Medicare. We've been meeting with payers to provide information about NPC and to introduce MIPLYFFA. And now that the product is approved, our payer team is following up with these customers to provide the additional information regarding the labeled safety and efficacy to help expedite coverage decisions. It's estimated that there are approximately 900 people in the U.S. living with NPC. However, only one-third of those, or about 300 to 350 people, are currently diagnosed and treated.
Until now, there were no approved products, and people living with NPC have been treated with routine care, including off-label miglustat. Our market research and real-world experience gained from our expanded access program suggest that approximately 80% of patients are currently receiving miglustat. We believe that the approved label will establish MIPLYFFA as the cornerstone of treatment for NPC, and physicians have told us that they are pleased and delighted to be able to use MIPLYFFA in combination with miglustat, and the payers have told us that they do not expect to restrict any access to the combination. As we've discussed previously, there are currently more than 70 people treated with MIPLYFFA through our U.S. EAP, which is being conducted in 13 sites across the country.
Individuals enrolled in this program have been receiving clinical benefit from MIPLYFFA, and our top priority will be to ensure continuity of their care as we transition them from clinical product to MIPLYFFA. We also know that there are other non-EAP subjects under the care of these same clinicians who are eagerly awaiting MIPLYFFA, and we will work in parallel to provide access for them. From there, we will expand our reach into other centers of excellence and additional sites where people living with NPC are treated. Additionally, we are working with clinicians through our medical education and advocacy efforts to increase the awareness and early diagnosis of NPC. With regards to product supply, we have ample supply, and we expect MIPLYFFA to be commercially available in the U.S. within the standard eight to 12 weeks after approval.
In establishing the cost of MIPLYFFA, we considered several factors, including the size of the eligible patient population and the clinical value MIPLYFFA brings to these individuals. We expect MIPLYFFA to be priced at $9.50 per milligram, with the wholesale acquisition costs ranging from $40,000 per month for the lowest dose to $106,000 per month for the highest dose. The exact dosage for an individual will be determined by his or her body weight, and the average price, based on dosing seen in our expanded access program, is expected to be approximately $85,000 per month. The wholesale acquisition cost does not consider additional coverage or support programs, and our top priority is to provide people living with NPC broad access to MIPLYFFA and to ensure that their experience is a positive one.
As a part of this commitment, we are pleased to announce the launch of AmplifyAssist, our patient support program offered through our specialty pharmacy partner, Orsini. The mission of AmplifyAssist is to provide personalized resources, such as support for insurance coverage, identification of copay and funding assistance, counseling on product, disease state, and therapy management, and assistance to address barriers to access and timely refills. Information about the program is available on our newly launched website, located at miplyffa.com, and healthcare providers can use this website immediately to complete prescription enrollment forms, which initiates the process for access to MIPLYFFA. This program will be an important resource in providing broad access to MIPLYFFA and underscores Zevra's ongoing commitment to assisting those whose lives are affected by NPC. So at this time, I'd like to open the call for Q&A. Operator?
At this time, the floor is now open for your questions. If you would like to ask a question at this time, please press star one on your telephone keypad. You may remove yourself at any time by pressing star two. Once again, to ask a question, please press star one. Our first question will come from Oren Livnat with H.C. Wainwright. Please go ahead.
Thanks for taking the questions, and congratulations on the major achievement here. Regarding combination therapy, can you just talk about why patients are not on miglustat now? Is it essentially just a off-label coverage issue generally, or are there other considerations that might limit people's ability to get on therapy, whether it's tolerability or others? And I guess, as you maybe mentioned in the script, does having this combination indication actually make it easier for patients to get on both a combination therapy than maybe even onto mono miglustat therapy before, given it's essentially now an on-label treatment? And I have follow-ups.
Good morning, Oren. Thanks for the question. And thanks for the congratulations. Last Friday was really a great day for patients living with NPC. The question around why folks are on or not miglustat, I think is multifactorial. As we mentioned in our prepared remarks, there are approximately 80% of the patients between our real-world evidence-
... with our EAP as well as in our clinical trial, that are on or have been on miglustat. And that sometimes we hear is based on tolerability, why the other 20% may not be there, as well as coverage issues. So there's some clarity that comes out of the label that we have. I'll bring it over to Josh to talk a little bit about combination and the access components. Josh?
Yeah. So just to reiterate what Neil said, there are a portion of patients who are not receiving miglustat because they have barriers to access, and it's not covered. With this label, those patients who have had some barriers, that will go away when it's prescribed in combination with MIPLYFFA. I can't speak to any access issues as it relates to miglustat monotherapy, but our research with payers has indicated that they are willing to pay for this combination, given the tremendous value that they've seen and that we've demonstrated in the clinical profile, showing more than a two-point improvement in the four-point domain, and that we've demonstrated that we halt the disease after 12 months.
And in your experience in trials, is there any difference in the process and success rates of initiating patients on therapy, with arimoclomol or MIPLYFFA, regardless of whether they're on miglustat or not? You know, I'm thinking about titration, the tolerability, if you saw anything there. And, just lastly, on the pricing, I really appreciate you guys coming out this quickly with the bookends there. Obviously, you haven't launched this thing yet, but can you give us any color around your expectations, you know, over time, maybe at launch and then maybe versus steady state, as to what do you think, I guess, net pricing or gross to net might shake out, all things being factored in?
Let me take the first one. I think I understood your question in regards to, the patients in our clinical trial program who, were on combination of the therapies and also in our EAP around titration and those things. From a clinical trial perspective, the trial was run according to protocol, and patients had to be stable on miglustat for six months prior to being randomized. In regards to our expanded access program, you know, the data is probably not as clean, but what I can say from the experiences that we've heard from both patients and clinicians at this point is that patients who tolerate miglustat seem to be able to stay on it. Others who have tolerability issues can come on and off of it.
Then those who have been able to be in our EAP program, we don't collect a lot of that data down to the titration on getting your miglustat up to 200 mg, three times a day or whatever it might be. So, I think we'll have to punt on the question in regards to the miglustat dosing, 'cause, you know, what we saw and what we continue to believe is that now that the combination is out there, you see that in the data of this, you know, greater than two points of progression with miglustat alone and primarily the halting of disease, when you bring arimoclomol and miglustat together. Let me hand it over to Josh for the, you know, pricing.
Yeah, and I think the second part of your question was around our expectations of price and GTN. And, you know, as noted, we've provided the range of pricing. I think important to note is that the price per milligram is what's gonna determine the overall price based on the weight of the patient. With regards to GTN, you know, we've presented the clinical data to payers, and they've expressed a willingness to reimburse, given the strength of the data that we've demonstrated. We... It's too early to give any indication on GTN. But, as a reminder, we do think that the average monthly price, based on the patients that we saw in our expanded access program, is about $85,000 per month.
All right. Thanks so much, and I'll talk to you guys after. Congrats again.
Thank you.
Thanks a lot.
Thank you. Our next question will come from Louise Chen with Cantor. Please go ahead.
Hi, congratulations on the approval, and thanks for taking my questions here. I wanted to ask you, on the patient, what is the annual cost to the patient or monthly cost to the patient out of pocket? Then just to confirm, you're assuming about $1 million per patient per year, just because you had mentioned that people come on and off miglustat, so I don't know if doctors would prescribe your product as monotherapy. Secondly, there's another NPC product that has a PDUFA date tomorrow, and just curious how that additional approval will impact the competitive landscape. Last question I had for you is: You currently have about 70 people on your U.S. EAP program that you said you'd convert to commercial patients within the first 12 months. In addition to that, that 300 and 350 patient population, how many would you add on top of the 70? Thank you.
Thanks, Louise. I'm gonna see if I can break this up by the four questions I think we got out of that. I'll ask Josh to talk a little bit about the out-of-pocket costs for patients. I will take the IntraBio. I believe is where you're asking about the PDUFA date for tomorrow and the competitive landscape. Then, I might ask Josh also to take the EAP transition question. Josh, you want to start with both of those?
Sure. So Louise, in regards to your question around out-of-pocket costs for patients, it's too early for us to be able to give any indication as to what the precise out-of-pocket costs will be. Having said that, we've put in place, through AmplifyAssist, a number of resources to bring that cost as low as possible, and that includes copay assistance programs. It includes a number of other things that patients can work with us through the AmplifyAssist to bring comprehensive care and comprehensive services to really try and minimize that out-of-pocket cost as much as possible.
With regards to the EAP conversion, as mentioned, you know, we have 70 patients today who are currently receiving MIPLYFFA and the benefits from MIPLYFFA, and so we want to ensure that those patients continue receiving care and receiving those benefits. And so, we will work as quickly as possible to get them converted to commercial products, while at the same time, working with other patients who are not on the EAP program to also get access to MIPLYFFA as well.
Louise, I'll try to take the question in regards to additional products coming with the PDUFA. You know, our goal here, and as we mentioned in the prepared remarks, and understanding that clinicians have always talked about the opportunity for multi-faceted treatment for Niemann-Pick C in this heterogeneous disease, we're hopeful that additional products do come to market. Just to clarify, though, I think it's an important perspective. You know, MIPLYFFA has really been brought to market based on the clinical trial that we did, and that is this revised four-domain, or sorry, rescored four-domain NPC-CSS, which is really a cornerstone now of disease modification and disease progression when it comes to an outcome. We're familiar with the other product that's got a PDUFA tomorrow.
Under our understanding is that it is based on symptom control versus disease modification. As we think about MIPLYFFA moving forward, with this magnitude of effect with MIPLYFFA and miglustat together, we see this halting of disease progression as a major milestone for the community.
Thank you.
Thank you. Our next question will come from Lachlan Hanbury-Brown with William Blair. Please go ahead.
Hey, guys. I'll add my congrats, and thanks for taking the question. So I guess I'm just curious. You said payers are amenable to covering both, but how does the requirements take with miglustat change that discussion at all? I mean, I don't know that I have many examples in mind of an approval that requires use of an off-label product with it. And I guess second, were there any post-marketing requirements that came through with the approval?
Yeah, I'll take the first question. So we did test with payers the combination of miglustat and MIPLYFFA. And their willingness to cover that stems from a couple of things. One is, keep in mind that they're already reimbursing 80% of patients today are already receiving miglustat, which is covered by payers, and they will continue to do that. But now with the added benefit that we confer with MIPLYFFA in combination with miglustat, there was readiness to continue to pay for that combination therapy.
Yeah, Lachlan, I'll take the next question. We do not have any post-marketing requirements. As part of our conversations with the agency, we have agreed to do a post-marketing commitment of a drug-drug interaction study with the combination of MIPLYFFA and miglustat, but we do not have a post-marketing requirement per se.
Got it. Thanks. That's helpful. And I guess another, if I may, just you've talked about there being 300 to 350 diagnosed patients in the U.S. Can you maybe elaborate on... I mean, are they all treated at centers of excellence? Like, do you know sort of who they are, where they are? And then maybe also elaborate on what you're doing to find the rest of the sort of 600-ish that should exist.
Yes. So the current 300-350 patients, we know where most of those patients are being treated. This stems from our strong relationships with the patient advocacy groups, and then through that, we have great familiarity with these patients and their families, and we also know that most of these patients who are currently diagnosed are being treated at these centers of excellence, where these world experts are taking care of these patients. In addition, as mentioned, there's, you know, roughly another 500-600 patients who are not diagnosed, and the diagnostic journey can oftentimes take five to six years before a patient is definitively diagnosed with NPC.
And we are working with the patient advocacy groups and through our medical education efforts to help identify those patients earlier by supporting things like newborn screening to make sure that NPC genetic testing is a part of that screen. We're working with clinicians to impact guidelines, which will help with the diagnosis or help with earlier diagnosis of these patients. And then moreover, we know that once a new product enters the market for which there had been no previous approved therapies. Just having a product that treats this disease will also help increase the awareness and the diagnostic rates as well.
Oh, thanks!
Thank you. Our next question will come from Sumant Kulkarni with Canaccord. Please go ahead.
Good morning. It's nice to see this approval come through for patients with Niemann-Pick, and thanks for taking our questions. I have two. First is a clarification, and apologies if I missed this, but how many total centers of excellence exist, and how many centers do these 70 patients in the expanded access program span?
Good morning, Sumant. Yes, so 40 centers of excellence, approximately 40 centers of excellence in the US. Our EAP program is active in 13 sites. We've said 14 total. One of those sites has not been active, so we have 13 sites in the U.S. who have been actively enrolling patients. That might be some of the disconnect there. So 40 overall centers of excellence, 14 total, but only 13 have enrolled patients.
Got it, and then, given this is going to be mostly combo use for the label, what's the potential for Zavesca or miglustat generic prices to migrate upwards, and have payers contemplated such a scenario that may be outside of Zevra's control?
Sumant, we do not anticipate that prices are going to migrate upwards. There. As you know, there are a couple of branded products for miglustat, but this is a heavily genericized market, and we do not anticipate that pricing is going to increase.
Thank you.
Thank you. We'll take a follow-up question from Oren Livnat with H.C. Wainwright.
Thanks. I forgot to ask earlier, you mentioned in the script the split between commercial and Medicaid, Medicare, I think the latter having about 45% of the population. Can you just remind us the expectations around timing to coverage there? Normally in the non-ultra-orphan space, you know, we expect a lag there, you know, with a calendar year reset and, you know, after an April filing. Is that different in this? I assume it's different than in the ultra-orphan space. Can you talk about what kind of coverage you expect there versus commercial and timing of that?
So thanks, Oren. Well, I'll ask Josh to talk a little bit about the split and where we see, but in regards to, you know, timing of coverage on the government side, the Medicare and Medicaid side of the house, you know, one of the opportunities we have with now disclosing the price is our opportunity to be able to, prior to October first, get into compendia listing and accelerate that process. Josh, maybe you want to add a little bit on the rest of the payer side of the house.
Yeah. So as noted, it's 55% commercial, 45% Medicaid and Medicare. And as you rightly note, there's sometimes variance in terms of loading the price and then getting coverage, and that varies, typically state by state. The advantage of us, and we're fortunate to get approval before the end of this month, so we are able to load the price into the compendia before the deadline to be able to get as expeditious coverage with Medicaid and Medicare as possible.
Okay, thanks so much.
Thank you.
Thank you. I would now like to turn the call back over to Neil McFarlane for any additional or closing remarks.
Thank you, operator. This is an exciting time for Zevra as we continue to make strides towards achieving our mission of building a leading, patient-focused, rare disease therapeutics company. The goals in front of us are to execute our launch strategy, work closely with the medical community to support its use of MIPLYFFA as a cornerstone of NPC treatment, and also to take this opportunity to celebrate with the NPC community for its relentless pursuit of a new treatment. I want to thank you all for joining us this early Monday morning, and have a great rest of your week.