Good afternoon and welcome to Ionis conference call to discuss the FDA approval of Tryngolza. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.
Thank you, Constantine. And thank you to everyone who has joined us today as we discuss the FDA approval of Tryngolza, the first treatment ever approved in the U.S. for adults living with Familial Chylomicronemia Syndrome, or FCS, as an adjunct to diet. Please be sure to visit the Investor section of the Ionis website to see the press release Ionis issued earlier today, along with the slides accompanying today's webcast. With me on the call today are Brett Monia, Chief Executive Officer, who will provide opening remarks. Sam Tsimikas, Senior Vice President, Global Cardiovascular Development, will discuss the severe manifestations of FCS and the positive data supporting the Tryngolza approval. And Kyle Jenne, Chief Global Product Strategy Officer, will review our comprehensive approach to achieve launch success with Tryngolza. And after Brett's brief conclusion, we will open the call for your questions.
Before passing the call over to Brett, I would like to remind you that our discussion today will contain forward-looking statements based on our current expectations and beliefs. Such statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail, and with that, I'll turn the call over to Brett.
Thanks, Wade, and thanks to everybody for joining us today. Today, we celebrate a historic milestone: the FDA approval of Tryngolza, the first ever treatment in the United States for familial chylomicronemia syndrome, or FCS. Tryngolza is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome. For the first time, adults with FCS have access to a treatment to significantly reduce triglyceride levels and substantially reduce incidence of life-threatening acute pancreatitis, which is strongly associated with this devastating disease. Tryngolza's approval is also a pivotal moment for Ionis. Ionis was founded on the principle of turning groundbreaking science and technology into life-changing medicines for devastating diseases. Spinraza and Tegsedi exemplify the power of Ionis innovation.
Nearly five years ago, we set a strategic course to fully maximize the value of our innovative medicines by retaining and delivering them directly to patients. Our Wainua co-commercialization partnership with AstraZeneca was a foundational step on this journey towards commercialization. Today, we enter a new chapter for Ionis as a fully integrated commercial stage biotechnology company ready to launch our first medicine, olezarsen, and olezarsen is just the beginning. Following closely behind, we are planning for three additional independent launches in the next three years: donidalorsen for hereditary angioedema, olezarsen for severe hypertriglyceridemia, or SHTG, and zepurenersen for Alexander disease. These programs collectively provide the opportunity to reach many thousands of patients with multi-billion dollar revenue potential. Following these initial launches, we have many more wholly owned programs advancing towards the market, positioning us for a steady cadence of independent product launches well into the future.
This includes ION582 for Angelman syndrome, the cornerstone of our wholly owned industry-leading neurology portfolio, which is on track to begin phase III development in the first half of next year. Ionis has long been at the forefront of pursuing diseases driven by severely elevated triglycerides, with essentially all of our discoveries published in highly reputable medical journals like the New England Journal of Medicine. We were the first to pursue ApoC3 as a target for triglyceride-related diseases. First, to demonstrate proof of concept in FCS patients by targeting ApoC3. The first to demonstrate reductions in acute pancreatitis through pharmacological intervention of elevated triglycerides. And of course, today, we are first to achieve FDA approval for a medicine to treat adults with FCS and bring it to the market. With our leadership in this therapeutic area solidified, we're ready to launch Tryngolza before year-end.
We're confident in Tryngolza's compelling clinical profile, and with Ionis's first-mover advantage and our world-class medical and commercial teams in place, we're very well positioned for success. Before concluding my opening remarks, I want to extend my heartfelt thanks to the patients, families, investigators, and research partners who supported the Tryngolza program and for those who participated in our clinical studies, all of which helped enable the approval of Tryngolza. Finally, I'd like to also recognize our team at Ionis, whose passion, dedication, and unwavering commitment to patients has contributed to this momentous day, and with that, I'll turn the call over to Sam.
Thank you, Brett, and hello to everybody on the call. I'd like to echo Brett's sentiments. All of us at Ionis are filled with pride as we deliver the first FDA-approved treatment for adults with FCS, their families, and healthcare teams. FCS is a rare, genetic, potentially life-threatening form of severe hypertriglyceridemia caused by a loss of lipoprotein lipase activity. This loss of activity prevents the body from breaking down dietary and endogenous fats, resulting in severely elevated triglycerides, often reaching levels 10 to 100 times above normal. Acute, recurrent, and potentially life-threatening pancreatitis is the most severe clinical manifestation of FCS. Sustained damage to the pancreas as a result of recurrent pancreatitis can lead to other comorbidities, including multi-organ failure. Acute pancreatitis events in people with FCS are also associated with more frequent hospitalizations and ICU admissions, as well as higher mortality compared to other causes of pancreatitis.
People with FCS are also burdened by a host of debilitating, sometimes daily chronic symptoms, including severe recurrent abdominal pain and nausea, impaired memory and comprehension, and severe fatigue. Many patients also report psychological and financial stress because of their disease, further adding to the impact FCS can have on patients' quality of life. Until today, there have been no treatments specifically approved for FCS in the U.S. Conventional triglyceride and lipid-lowering therapies, such as fibrates, omega-3 fatty acids, and statins, are minimally effective in lowering triglycerides in people with FCS. And a low-fat diet limited to less than 20 g of dietary fat per day is insufficient alone. A diagnosis of FCS can be made by several criteria: genetic confirmation or by clinical confirmation using diagnostic tools such as recently published North American FCS Score, or FCS Foundation.
The FCS Foundation was developed and validated as a clinical method to confirm FCS diagnosis and differentiate it from other forms of severe hypertriglyceridemia using specific clinical criteria, including young age of onset, persistent and recurrent triglyceride levels greater than 880 mg per deciliter, a history of acute pancreatitis with unexplained abdominal pain, refractory to standard lipid-lowering therapies, and no secondary contributing factors. Importantly, olezarsen's indication statement allows adults with genetically or confirmed FCS to benefit from this treatment. The positive data from the phase III BALANCE study, which was published in the New England Journal of Medicine early this year, formed the basis for olezarsen's approval. In the BALANCE study, olezarsen 80 mg, dosed monthly, compared to placebo, demonstrated significant triglyceride reductions in six months, which further improved through 12 months of treatment. Clinically meaningful reductions in acute pancreatitis and a substantially longer time to the first acute pancreatitis event.
A substantial reduction in all-cause hospitalizations and days spent in the hospital, and a favorable safety and tolerability profile in people with FCS. We believe the positive data generated from the BALANCE study underscore the tremendous benefit Tryngolza can bring to adults with FCS as an adjunct to diet. And now I'll turn the call over to Kyle.
Thank you, Sam. This is an incredibly exciting day as we enter a new era as a fully integrated commercial stage biotechnology company poised for success with our groundbreaking breakthrough medicine, Tryngolza. Tryngolza is the first FDA-approved treatment for adults with FCS. We believe its compelling profile, supported by comprehensive data from the phase III BALANCE study, will meet the needs of patients, prescribers, and payers that until now have not had an effective therapeutic option to treat this potentially fatal disease. Our commercial and medical affairs teams are fully prepared for launch before year-end. Patients in the U.S. are waiting for a treatment, so we are all systems go to get drug into the channel in the coming days, and importantly, we are entering the market with a significant first-mover advantage, enabling us to solidify our leadership position in this space well ahead of any later market entrants.
olezarsen's approval is based on positive results from the phase III BALANCE study, and importantly, olezarsen's indication statement enables adults with FCS to benefit from this treatment regardless of a genetic or clinically confirmed diagnosis. We believe olezarsen's clinical profile, including robust and sustained reductions in ApoC3 and triglycerides, acute pancreatitis outcomes, and favorable safety and tolerability, along with the convenience of once-monthly self-administration, will be a compelling treatment for adults with FCS. We believe the total addressable U.S. FCS patient population could include up to approximately 3,000 people. However, the vast majority of this population remains unidentified and undiagnosed today. As is the case with many rare diseases with no treatment options, FCS has been a largely unrecognized disease with a lack of awareness precluding patients from achieving diagnosis.
With this approval, we have the opportunity to transform the existing treatment paradigm and make a meaningful impact in the lives of adults with FCS. Upon launch, we intend to convert U.S. patients from our ongoing open-label extension study and expanded access program to commercial drug, and to support new patient starts, we plan to build upon our disease awareness efforts in order to help physicians identify, diagnose, and treat adults living with FCS. As FCS is a rare and under-recognized disease, we anticipate an initial gradual build-up of launch momentum. However, as our efforts lead to greater physician awareness, we expect the number of new patients diagnosed with FCS to increase, which in turn will translate to an acceleration of our launch progress.
We designed our olezarsen launch strategy for success with an organization singularly focused on the same goal: helping to bring olezarsen to as many adults with FCS as possible. This will be done with programs specifically designed to support patients, HCPs, and payers. This team of professionals, each with extensive experience in launching medicines for rare diseases, will drive patient identification and diagnosis, helping to ensure the uptake of olezarsen. Our medical affairs team has been in the field educating physicians about the risks of severely elevated triglycerides, including potentially fatal acute pancreatitis. With olezarsen now approved, we will build on these foundational activities through additional evidence generation, supporting independent medical education programs, and maintaining a strong presence at key medical conferences. Our commercial field team is trained and already actively engaging with HCPs who treat patients with high triglycerides.
In addition to supporting FCS patient identification, they will focus on communicating Tryngolza's prescribing information and ensure a seamless prescribing experience for physicians and their staff. We are deploying a suite of programs and services designed to further support patients and their care teams throughout the Tryngolza treatment journey. Through these efforts, we aim to strengthen Ionis's position as a trusted partner in the treatment of FCS. Our market access and reimbursement teams are mobilized and ready. During pre-launch engagements with a broad set of U.S. payers, we learned that they recognize the significant burden FCS places on patients. We plan to leverage these learnings as we work to support timely and straightforward access for eligible patients. Finally, we will use omnichannel capabilities to engage patients and physicians and extend the reach of our commercial team.
Supporting patients and healthcare providers throughout the treatment journey is central to our commercial strategy. Ionis EveryStep is our patient and HCP support program that we designed to meet the unique needs of the FCS community. As part of Ionis EveryStep, people prescribed Tryngolza have access to a suite of services designed to help them start and remain on treatment. These services, provided by dedicated patient education managers, include guidance in achieving reimbursement, disease and nutrition education, autoinjector training, and more. For HCPs, Ionis EveryStep streamlines the Tryngolza prescribing process by offering insurance authorization and reimbursement assistance, as well as coordinating delivery of Tryngolza, reauthorizations, and refills for patients. Tryngolza is being launched with an annual price of $595,000, reflecting its clinical value for the rare FCS patient population who face significant unmet medical needs.
We are committed to ensuring Tryngolza is affordable for patients who need it and have established financial assistance and reimbursement support programs. For eligible commercially insured patients, these programs can reduce out-of-pocket costs to as little as $0 per prescription. Before turning the call back to Brett, I want to emphasize our excitement about today's approval and the opportunity it brings to serve people with FCS. The FDA approval marks a pivotal moment on our journey to launch our innovative medicines independently and positions u s well for success. Tryngolza's compelling profile, combined with a highly skilled commercial team, gives us strong confidence in our ability to successfully execute on Ionis's first independent commercial launch. We are equally optimistic about our future commercial success as we prepare for a steady cadence of independent launches to follow. With that, I'll turn the call back over to Brett.
Thanks, Kyle. With the approval of olezarsen and our impending commercial launch, we have fulfilled our promise to evolve Ionis into a fully integrated commercial stage biotechnology company. This pivotal achievement reflects our unwavering commitment to maximize the value of our innovative and transformative medicines by delivering them directly to patients. Our efficient and scalable commercial organization is not only ready for the imminent olezarsen launch but is also primed for the next wave of innovative medicines nearing commercialization. Donidalorsen is on track to become a new prophylactic treatment for patients with HAE with anticipated approval next year. olezarsen for SHTG represents our first opportunity to address a highly prevalent patient population with phase III data expected in the second half of next year. Additionally, zepurenersen, a promising therapy for Alexander disease, is on track for phase III data next year.
Following these potential launches, we have a rich and growing pipeline of wholly owned medicines that put us on track for commercial success well into the future. Together with olezarsen, these advancements position us to achieve up to four independent commercial launches by the end of 2027. Collectively, these therapies provide multi-billion dollar revenue potential, marking an exciting new chapter for Ionis. And with that, we'll now open the call up for questions. Operator.
Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number two. If you are using a speakerphone, please make sure you lift your handset before pressing any keys. Your first question comes from the line of Mr. Gary Nachman from Raymond James. Please go ahead.
All right. Great. Congrats on the approval and what seems to be a good label. So a few questions. First, the indication seems broad across FCS, as you said. So it doesn't specify genetically or clinically confirmed diagnosis. So how much does that help in targeting FCS patients? Just give us a little more on where the diagnosis rates are now, and what will you do to try and improve those? So that's first. And then regarding the mention of the reduction in the acute pancreatitis in the label, what portion of the 3,000 patients with FCS could be at risk for acute pancreatitis? So just how important is that angle for this drug? And maybe comment how costly it is in terms of the hospitalization relative to the pricing that you mentioned.
Thank you, Gary. So there's a lot in there. All good questions. I'll start with talking a little bit about the importance of the broad label with respect to genetic and clinical diagnosis. And then I'll ask Kyle to comment on how we're going to find these patients, diagnosis rates, and maybe Sam could talk a little bit about the risk of acute pancreatitis and why that's important to have that in our label. So first of all, the majority of patients with FCS, we believe, will be genetically diagnosed. There are pretty straightforward methods for genetic diagnosis, and it is a definitive diagnosis that coupled with triglycerides above 80. However, a lot of patients have what we refer to as indeterminate genetic outcomes in the genetic assessment. In those patients, a clinical diagnosis is very important.
As Sam mentioned in his readings before, patients can be diagnosed clinically using the North American FCS criteria that's now been published to get a treatment to these patients. The other thing that's important to recognize is that many of these patients are not diagnosed yet. It's still uncertain how many patients, like what percentage of patients, for example, would be clinically diagnosed versus genetically diagnosed. There can be a large amount of patients that are a relatively large amount of patients that are clinically diagnosed. That's why having the ability to deliver Tryngolza to both sets of patients is really important. Kyle?
Yeah. So I think it's really important that we have a broad label here. It really does help us. I mean, the genetic confirmation is something that we've been pursuing, and obviously, that was the basis of the clinical trial. However, to be able to clinically diagnose these patients, number one, it allows a scoring tool that is easily used by the physician to be able to work with these patients to understand if they're potentially FCS patients or not. So that's going to help us accelerate finding these 3,000 patients. We've already seen that in the last month or so as the field teams have been deployed and using the tool that was published in the Journal of Clinical Lipidology.
What that's allowed us to do is to have something to talk to physicians about in terms of how to use this, what to look for, and then if you do find it, to go ahead and move forward with genetic testing if appropriate. The other area that this is really going to help us with is with payers. Once these patients are identified and we see diagnosis rates start to go up as they submit their prior authorizations and prescriptions through to the payer side, it's really going to help us be able to justify to the payer that these are appropriate patients that should be treated and should be reimbursed by the insurance plan. Really key tools, and I think you will see an acceleration of not only diagnosis rates but identification of these patients now that we have an approved medication for FCS.
Jonathan, if you want to touch on hospitalizations, that would probably be helpful as well.
Thanks, Kyle. Yeah. The BALANCE data that was published in the New England Journal demonstrated the significant reduction in the hospitalization rate that is a result of the complications of FCS, particularly AP. Critically for payers, we saw a six-day reduction in the length of stay, which is very meaningful from an economic point of view, not to mention the benefit this provides for patients.
Yeah. And I'll address the question about acute pancreatitis and kind of its impact on the healthcare system. If you look at the studies that we published and others, about three-quarters of these patients end up getting pancreatitis at least once in their lifetime. In fact, in our study, the average number of episodes was five to six. These patients also tend to be fairly young, so they end up staying in the hospital about six days on average. And the mortality rate actually of acute pancreatitis can be as high or higher than acute myocardial infarction now, 4%-8%. So if you have multiple episodes, you're young, it impacts not only the hospitalization cost, but the cost to society. They lose work, they have to take care of their kids. It's a major impact on the whole kind of family, not just those patients themselves.
It's a major issue. The patients also self-treat themselves often at home and try to avoid hospitalization, so it has a huge impact on them in that way. I think reducing pancreatitis is going to reduce hospital stays. We already documented. It probably will reduce mortality when we can get enough data, and it will reduce hospitalization costs tremendously if you add up how many times they get hospitalized throughout their lifetime.
Thank you, Gary.
Great question.
Yeah. Thanks for all that color . Thank you.
Your next question comes from the line of Yanan Zhu from Wells Fargo. Your line is now open.
Oh, great. Thanks for taking our questions and congrats on the approval. Maybe a question on the label. The label looked very clean, but I do wonder if you can comment on. There's a section about lab numbers. There was mentioning of platelet, LDL, and the information provided there. Could you comment on if there's anything of note? Also, if you don't mind, can you comment on the competitive dynamics given that Arrowhead has submitted its BLA also? So going forward, how do you see the launch and how the approval of the Arrowhead product potentially impacts the patients you have already put on commercial treatment or affecting discovering new patients? Thank you.
Thanks, Yanan. We couldn't be more pleased with the label. It is very clean, as we expected, as we see with really we've been seeing with all of our new GalNAc drugs that have been approved or are in phase III development today. It sets us up very well to take advantage of our first-to-market opportunity, our first-mover advantage, and that's really all I'm going to say about competition. We have a great label. We have a broad label with respect to the indication statement, and we have a very clean label, and we have first-mover advantage. With respect to platelets, I'll touch on that, and then Sam can talk about the impact, his view on the LDL in the label, so on platelets, these are fluctuations that were very infrequent, rare, mild, not clinically meaningful, and often transient. They typically resolve with continued treatment.
We saw no patient risk attenuations, no clinical consequences, no monitoring requirements post-approval, and no post-marketing studies that are necessary to examine platelets longer term. So platelets are not clinically meaningful, and we don't think they're going to have any bearing on the commercial success. And maybe I'll turn it over before you, Sam, to Kyle to touch on the label and how he sees it setting us up for success commercially.
Yeah. So I mean, first, being first-to-market, I think, is really key here, as Brett just mentioned. Tryngolza has a very compelling profile here. To be able to confirm these patients through either genetic or clinical diagnosis is going to be key. That's going to allow us access and clarity around treating the right patients, which I think is very important. When you see the reduction of ApoC3, the reduction of triglycerides, the reduction of acute pancreatitis events, these are all very, very meaningful and very valuable, I think, and you see that read-through in the clean label that we're just talking about. The other key component here is the convenience of the monthly self-administration with an autoinjector. This is going to be a very simple-to-use device for patients to be able to administer on a monthly basis, and we think will be very attractive for patients.
The last thing I'll mention before turning it over to Sam is under the patient counseling section. I think it's going to be very easy for physicians to speak with patients about olezarsen. They're going to advise the patient, obviously, on the label. They can talk about hypersensitivity and what needs to happen if that occurs, the adherence to diet, which is a component of the indication statement. If they miss a dose, they can take the dose as soon as possible, and then they follow just the regular monthly schedule moving forward. I think the patient counseling session really speaks to the ease of use and the conversation that's going to take place between the physician and the patient. Sam?
Yeah. On the other laboratories that you brought up, the liver test, the glucose, and the LDL, these essentially happen in the normal range. So they're part of the laboratory measurements, but they're not clinically relevant. We don't think they're going to impact how physicians look at this drug or have any fear in prescribing it. The glucose happened in the normal range. It actually didn't even happen in patients with diabetes, interestingly. The LFTs were happening also in the normal range, so they're not like three times above normal where we get worried, and the LDL in these patients started very low at 50 mg, which is like the lowest you could essentially get, and they went to 30, and that's just kind of recalibration of how lipids are metabolized. It's not like going to 190 or something where you really have to worry about it.
Bottom line is I don't think we need to worry about those lab tests. They're good for physicians to know about it because patients have other issues that come up, but they don't need to monitor for them on a regular basis or worry about them.
Thank you, Yanan.
Great.
Your next question comes from the line of David Lebowitz from Citi. Please go ahead.
Thank you very much for taking my question. From the payer perspective, while a genotype or genetic diagnosis of a patient would be clear-cut, how are they looking at the scoring methodology for clinical diagnosis with respect to reimbursing for those patients?
Yeah. Thanks for the question, David. We've been working a lot with payers leading up to this. As you're well aware, we've been having discussions about the value of this treatment. They understand the purpose of treating FCS. They understand the rarity of the disease. And from a reimbursement standpoint, we've had very positive conversations about the criteria for use up to this point. They want to make sure that these are FCS patients. And to your point, they can be identified through two different ways, as we've been discussing, through either genetics and/or clinical confirmation. So it will be payer-dependent, we believe, in terms of how they establish their criteria for use. Some might require a genetic test.
And if that genetic test is indeterminate, then the scoring criteria would be the default way of being able to justify that these are FCS or true FCS patients that should be reimbursed. So it'll vary a little bit, but it will be genetic testing and/or the clinical scoring tool that's recently been published that will be able to justify the appropriate patients getting on treatment through the payers.
Thank you for taking my question.
Your next question comes from the line of Myles Minter from William Blair. Please go ahead.
Hi. This is Jake on for Myles . Thanks for taking my question. I wanted to ask a little bit about the launch. Do you see the launch in FCS as synergistic with a potential launch in SHTG, or would approval in that indication after these phase III studies in 2025 require additional infrastructure and significant additional SG&A spend? Thanks.
Thanks for your question. Yeah. I think there's a huge amount of synergy here. I think we've been building our commercial capabilities over a number of years and certainly have all the key functions in place. Directly to the second indication, the SHTG indication, I think there'll be a huge amount of synergy. We'll be able to leverage a lot of the team that's already in place and obviously scale it appropriately to meet the SHTG opportunity. But without doubt, you're right. There's a lot of synergy as we scale up for that larger indication.
Thanks for the question, Jake. Next.
Your next question comes from the line of Yaron Werber from TD Cowen. Please go ahead.
Hi. This is Joyce on for Yaron. Thanks for taking our question and congrats on the approval. How quickly can you convert patients that are currently on drugs through the open label extension or the expanded access program to commercial drugs? And then just more broadly, as first-to-market, can you just discuss what you're doing in terms of outreach and messaging or anything else to help set yourself apart while you're the only approved drug on the market? Thank you.
I think for those patients today who are already being treated via our development program, the principal investigators have already informed that these patients will transfer once the launch is in place. Obviously, these patients are our number one priority as we engage with the principal investigators of those studies. So they're the number one priority for us next week.
Yeah, and just as a reminder, those will be patients in our open-label extension and our expanded access program that are in the United States that we'll be converting over, and we'll be converting them over relatively quickly.
Yeah, and I'll just add, we were talking about patient finding, and I mentioned some of this in my remarks that were prepared, but this is going to be a gradual build over time. Without an approved therapy up until today, there's been really no reason to diagnose and treat these patients because there's not been a great way to do that, no really effective treatments. All you could do is have an extremely low-fat diet of less than 15-20 g of fat per day. Now that Tryngolza is available, we expect that the interest in actually diagnosing and going through the process of using the scoring tool and/or genetically testing these patients will accelerate. That will take us some time to get there. We believe that this launch will build over the course of the next year or so.
We're very encouraged by having the first-mover advantage and by having a very strong label and clinical profile like we do in the label for Tryngolza today. We're really excited about this opportunity and the launch.
Great. Thank you.
Your next question comes from the line of Jason Gerberry from Bank of America. Please go ahead.
Oh, hey. Good afternoon. This is Chi on for Jason . Thanks for taking our questions and congrats on the approval. I have a three-part question on acute pancreatitis data on Tryngolza, if I may. First is, can you talk about how meaningful it is to have the acute pancreatitis data in the clinical section of the label as it pertains to your ability to communicate the benefit to physicians? And secondarily, what are your expectations that the acute pancreatitis data would not be included in the front page of the label? Do you think this is a class-specific or drug-specific label treatment by the FDA? And thirdly, if you can't detect an acute pancreatitis benefit in your SHTG trial, would you expect to have the acute pancreatitis benefit in label indication on the front page of the label? Thanks so much.
I'll just start, Chi. Thank you for the question, but then I'll ask my commercial colleagues to talk about how meaningful it is to have the AP data in the label. We're very pleased with where the AP data is in the label. The indication statement is broad, and we believe that having this data in the label will just solidify what's already been very well received in the cardiometabolic community from the New England Journal of Medicine data that we published earlier this year that really demonstrated a substantial reduction in acute pancreatitis events, so we're very pleased with the fact that this data is in the label. We were expecting it to be in the label. Of course, you never know until the label is complete, and where it lies in the label is just fine.
We're going to do a great job in delivering this medicine to patients based on the triglyceride reductions, based on the AP data that's in the label, based on our publications, based on the reductions in the hospitalizations that we showed in the New England Journal of Medicine, and based on the clean safety profile. With respect to SHTG, it's a randomized ongoing phase III clinical trial with data expected in the second half of next year. We expect that there's going to be plenty of AP events in that study. Although the rate of AP is somewhat less in SHTG than it is FCS, our clinical trial is more than 10 times the size. So we will be and are accumulating AP events in this study. And we're reasonably confident we're going to see a really meaningful benefit in AP reductions in SHTG just like we did in FCS.
and that'll be important. Comment on how important this is from a commercial perspective, Kyle?
Yeah. I think it's very important. Sam just walked us through what happens when you have triglycerides at these levels that we're talking about. And the risk of acute pancreatitis is really, really important to the physicians that are treating these patients. And it's really important to the patients, obviously, that are being impacted by this, with acute pancreatitis not only potentially being recurrent, but potentially fatal. And so that being in the label is a very, very important part to the story and very important for physicians and patients and payers to realize what our actual rates were. And to have one patient in the olezarsen group have pancreatitis and seven patients in the placebo group that had pancreatitis just speaks to the amount of effect that olezarsen had and the positive outcome for these patients by being on drug.
The other key thing is the time to that event. And the time to event on the patients that were on olezarsen was much longer and much greater delay than the patients that were in the placebo group. So that information, we think, is going to be very valuable and important in terms of not only selecting the right patients to treat and why to treat those patients, but also what the clinical trial showed in terms of outcomes for those patients.
Great. Thanks so much, Kyle. Once again, on the approval.
Thanks, Chi. Thank you. Next question.
Your next question comes from the line of Mani Foroohar from Leerink Partners. Please go ahead.
Yeah. Congrats on the approval and the clean label. I was hoping to dig in a little bit on how to think about launch dynamics in a little bit more of a quantitative way. Can you give us a sense, either approximately or precisely, if you can disclose that, the size of the population of patients in the EAP/part of the ongoing clinical population, time horizon over which you would expect them to transition onto commercial drugs, and to what extent that's influenced by payer mix, etc.? And if this varies by geography, that would be great to know as well.
Yeah. I'm happy to take that. This is Kyle. We don't want to speak specifically to the size. This is going to be a competitive marketplace and a competitive situation here. So the numbers in terms of how many are currently either in the OLE and/or EAP, we're not disclosing. The time to transition is as soon as possible, right? We now have a commercially available drug. Physicians have been notified that if they have these patients and if and when the Tryngolza becomes available, that we would begin to transition these patients. But I'm a little cautious about setting a specific timeline because there are some dynamics that have to occur within the physician practice to get these patients in, to get the prescriptions written, and then to navigate the prescription process, as you just described, from a payer mix standpoint. The payer dynamic is still unknown, right?
With the approval today, we're going to have to go back to the payers and speak with them about these specific criteria that they're going to put in place. Keep in mind, there are upwards of 10 drugs that are being approved here at the end of the year, and that puts a lot of pressure on the payers to figure out which drugs to review and when to review those drugs.
The positive thing that we're hearing from the payers is FCS and Tryngolza, the way that the clinical profile was setting up and the information that the payers were seeing. They don't feel like this is a big rush to review this drug really, really quickly because they believe that through the scoring tool and through the genetic confirmation, through the indication statement, that they will have the right patients being prescribed Tryngolza in order to reimburse and support those patients. The payer mix, I think we will navigate and be able to do effectively, keeping in mind that we're going to have programs to get these patients started on treatment very, very quickly once they receive a prescription. That's part of our program to make sure that patients and physicians have a way to get on drug quickly.
And geographically, it's spread out all across the United States. It's not concentrated in a respective geography or in one or two centers. We know that there are patients broadly from New York to California over to Florida, etc. So it's going to be a mix of payers, regional dynamics, etc. But we feel very good about now that we have the label and we know what the label states, to be able to justify, treat the right patients, get those PAs submitted, and begin working with payers to get these patients on prescriptions as soon as we possibly can.
Just to add to that, Mani, just as a reminder to everybody, our medical affairs team has been out in the field for about two years plus now and really talking about how to diagnose patients with FCS, what to look for, and to really identifying those treaters that manage FCS patients today. So we want to get to those centers of excellence and those other treaters that manage FCS patients as quickly as possible. We've identified a lot of them. Now that we have the approval of Tryngolza, our job is now to get those treaters in the U.S. writing those scripts.
Yeah. I'll make one more comment about the Ionis EveryStep program. I think it's really going to be key for us to support both patients and HCPs as they begin writing these prescriptions. We've got really tremendous programs in place, including reimbursement support. Commercial patients could pay as little as $0 for their co-pays if they qualify. And we believe that this is going to be an opportunity to get patients on drug in an affordable way for them to be able to do so.
That's helpful. Thanks, guys. Congrats again.
Thank you.
Your next question comes from the line of Luca Issi from RBC. Your line is now open.
Oh, great. Thanks so much for taking our questions. This is Lisa for Luca, and I will extend my congratulations on the approval here as well. Just a few questions on the launch and one on safety, so just wondering if you can give us a ballpark number on how many physicians you plan to target for the FCS launch and about how many salespeople or MSLs do you think will be needed, and as well, I'm just wondering maybe for modeling purposes if you can give us an idea of what you anticipate the gross to net may be. I understand it might be a little bit early to ask that question, but I'll ask it anyways, and on the injection site reactions that are on the label, can you remind us how you are advising physicians to manage those AEs?
And what was the patient experience like in the BALANCE study? Thanks so much for taking our questions.
We'll start with the injection site reactions, Sam.
Yeah. The injection site reactions in general were mild and fairly tolerable. And so most of them consisted of itching, redness, maybe a little bit of swelling. So we're advising physicians to just keep an eye on them. There's not a lot you can do. They're usually self-limited, but local measures can sometimes help, like ice, for example. But they didn't really lead to any major discontinuations that were broad or any major issues. They were mild and self-limited. So I think it's not going to be a major issue. It is an injection. It is a needle. And you can see also the placebo group has some of those also.
Yeah. And I'll just make mention Wainua currently is on the market, and it's using the same autoinjector. And patients are learning how to use it very effectively and seem to be well tolerated. So we expect that will carry over, obviously, to the Tryngolza program. Jonathan, do you want to touch on the commercial aspect?
Yeah. I think the question was on sizing. I think we've disclosed in the past that we've got a field team that's between 20 and 30 individuals that will give us the coverage of what we believe the top 1,500 lipidologists in the country, whether that's endocrinologists or cardiologists. Obviously, beyond that, as we learn and diagnose more patients, we'll flex and expand that reach.
Yeah. And I'll just add one thing about our omnichannel capability as well. It's not just about how many feet on the street we have per se, but it's about all of the programs that we have in totality to be able to educate the community, not only physicians, but also patients and caregivers, and mobilize them. And so we have some really, really, I think, innovative and key programs that'll help us expand our reach and get to a pretty broad audience of potential treaters.
Lisa, we're not sharing the gross to net numbers at this time. Thanks for the questions. Next.
Your next question comes from the line of Ellie Merle from UBS. Please go ahead.
Hi. This is Jasmine on for Ellie. Thanks so much for taking our question and adding my congratulations on the approval. So it seems like physician awareness is going to be a really important lever here to increase diagnosis. Can you give any color on some of the other key leaders you're targeting to get diagnosis numbers up? And any additional color specifics on how you're planning to address these? And how should we think about kind of the cadence of the diagnosis increasing? Thanks.
So diagnosis rates today, as I mentioned, are fairly low. We've got about 3,000 potential patients, as I outlined. We believe that diagnosis rates will accelerate fairly quickly now that Tryngolza is approved and there's a treatment available to help these patients potentially with their FCS disease. And so I believe out of the 3,000 at this point, I'm speculating here, but there are probably a couple of hundred that are currently identified. There are a lot more that are potential FCS patients. And that's the work that we're doing right now is to get in front of these physicians and have the right conversations about the potential phenotype, putting them against the scoring tool, using the genetic testing services that are available, and trying to confirm those patients.
So I think a combination of awareness and the acceleration of our field teams being out there, our omnichannel, and the other marketing efforts that we're doing to make sure that awareness goes up, combined with the tools and resources that we've been discussing with the FCS Foundation, etc., I expect those diagnosis rates to go up fairly quickly. But it's going to take some time, right? And it will be a steady build, we believe, over the course of next year in order for us to continue to capture a growing portion of this market.
But there is an urgent unmet need. We're already seeing with our engagement with HCPs, this is a real problem for them to manage these patients. So that already exists. And I think once they understand and become aware of the launch and they know there's a potential solution if they can diagnose these patients, I think to Kyle's point, that diagnosis rate will accelerate.
Thank you, Lisa, or Jasmine. Thank you, Jasmine. Next question, please.
Your next question comes from the line of Yale Jen from Laidlaw and Company. Please, go ahead.
Thanks for taking the questions and also add my congrats on the approval. Just two quick ones. The first one is that although we all talk about the U.S. right now, what's the current thoughts of steps for the European strategy? And then I have a follow-up.
Yeah. So we are under review in Europe for approval. And we are, as you know, Yale, our initial launches for Ionis will be focused on the U.S. market. And we will secure outside the U.S. commercial partners. We're well on our way to securing an ex-U.S. partner for Europe, for olezarsen, for Tryngolza, I should say. And we've already secured a partner in Theratechnologies for Canada. And they will be responsible for the application in Canada and commercialization there. So we're well on our way.
Okay. Great. Maybe a follow-up here is that it's very impressive in terms of almost 60% reduction in triglycerides in 12 months. Just curious, in the real-world practice going forward, is there an absolute level of TG that a patient could, for example, have a treatment holiday, or they should continue their treatment 12 months, a year, continuously? And thanks.
Yeah. This is Sam, my comment to Yale . I think the triglycerides will come back up. And these patients are very, very sensitive to dietary triglycerides. So we're not going to recommend they have any kind of holiday. They have to be on the drug, take it every month, and also watch their diet to minimize the risk of pancreatitis.
Yeah. Very important.
Okay. Great. Thanks.
Your last question comes from the line of Andy Chen from Wolfe Research. Your line is now open.
Hey, thank you for taking the question. And congrats on the approval. So we know your price for FCS, just trying to be future-looking here. Is there some creative way where you can keep your pricing high for FCS while in the future lowering the price only conditionally for high trig in order to preserve the value of the FCS market? So we're suggesting indication-based contracting. We know it's tough, but it's certainly possible and a good idea. So curious about your thoughts on the feasibility of this. Thank you.
Yeah. I think the challenge here with this is the size of the patient population whenever you get into SHTG and the prevalence and the budget impact that that's going to have on the payers, and when you're talking about a few thousand patients versus potentially a few million patients when you get into SHTG, the price is going to have to come down. Typically, you can do that through two ways, as you just indicated. You can either cut price and bring it down, or you can do it through discounts and rebates. I think the discounts and rebates are going to be really tough when you're going from the $595,000 range down to more of a specialty cardiovascular pricing range that you're going to need to be at in order to justify this to the payers from a budget impact standpoint when you get to the next indication.
So we'll navigate that. There's more to learn. Obviously, we've got some work to do with the payers over the next two years as we get to potentially SHTG. But we're very excited and pleased with where we're at right now with FCS and the pricing. And we believe that it obviously justifies the value that the medicine brings for these patients. And we'll work with the payers to make sure the reimbursement goes smoothly.
Thank you, Andy. And I want to also thank everybody once again for joining us on this exciting day, an exciting day for the FCS community, an exciting day for Ionis. I'd like to wish everybody on the call and everybody listening out there today a happy holiday season. We look forward to seeing you and sharing additional updates from Ionis next year. Take care, everybody.