Great. Welcome, everyone. My name is Jessica Fye. I'm a Senior Biotech Analyst at JP Morgan, and we're continuing the 42nd Annual Health Care Conference today with Ionis. I'm joined on stage by the company's CEO, Brett Monia. We're going to have a Q&A session after he gives a presentation on the business. If you want to ask a question, just raise your hand, someone will bring you a microphone, or you can submit questions over the portal. So with that, let me pass it over to Brett.
Thank you, Jess. Thank you, JP Morgan, for the opportunity to speak today on the great progress we're making at Ionis on behalf of the company. You know, Ionis today, I'm very excited, very pleased to be presenting on the progress we're making at Ionis as this really great company enters into a new era. An era that's poised to transform human therapeutics, to unlock better futures for patients, and also to drive next-level value for all stakeholders. During my presentation, I will be making forward-looking statements. So at Ionis, we have been and will continue to drive great value for patients and for all stakeholders by continuing to execute on a clear vision.
A vision to produce and to deliver a steady cadence of new treatments, new medicines for patients suffering with debilitating diseases, each of which has the potential to be transformational in its own, in its own right. We have been doing this, and we will continue to do this by focusing on three strategic objectives. The first is to prioritize the Ionis wholly owned pipeline. The second is to take advantage of the commercial capabilities that we now have in place at Ionis to deliver medicines from our wholly owned pipeline directly to patients. Thirdly, to extend and expand our leadership position in oligonucleotide therapeutics by expanding our drug discovery capabilities through technology, innovation, and advances.
All of this underpinned by our financial stewardship and our strong financial position that enables us to make all the investments we need to make to ensure for continued success. We are, 2022 was a remarkable year of achievement, or 2023 was a remarkable year of achievement for Ionis against a very ambitious set of goals that we set at the beginning of the year. This is just a snapshot of some of the accomplishments, strategic accomplishments that we achieved in 2023 by the numbers, if you will. In 2023, we achieved two FDA approvals. In the first half of the year, QALSODY for SOD1-ALS, and then right at the end of the year, WAINUA was approved by the FDA for a rare severe disease called ATTR polyneuropathy, which really capped a truly remarkable year right at the end.
In addition, we had two very[positive] phase III readouts in 2023. The very[positive] phase III results for WAINUA in TTR polyneuropathy that was demonstrated at week 66 at the completion of the study, which then was reinforced at week 85. In addition, we reported very[positive] phase III data for Olezarsen, our treatment for FCS from phase iii BALANCE study. We also initiated three phase III programs in 2023 in HBV, IgA nephropathy, and in Alexander disease. We completed enrollment in four very important clinical trials, including phase III trials, our phase III trial in hereditary angioedema and our landmark CARDIO-TTRansform study for patients with ATTR cardiomyopathy. We had several additional positive clinical readouts as well.
All of this created momentum and sets us up for an even more exciting and eventful, strategically eventful year for 2024. And these are, again, some of the highlights that we're anticipating that's going to happen this year, that are really going to drive the needle in our view. Two new commercial launches, including our first independent commercial launch by end of the year for Olezarsen in FCS. We're looking forward to presenting two phase III readouts this year. The full data set for BALANCE for Olezarsen in FCS, as well phase III data for Donidalorsen in our OASIS-HAE trial in hereditary angioedema.
We're looking forward to two NDA filings this year for FCS, for Olezarsen and HAE for Donidalorsen, and also, from our mid-stage pipeline, several, five actually, clinical readouts that are expected this year four programs of which can go phase III, advance phase III, development, assuming the phase II studies support that. And several additional regulatory filings and approvals, both in the United States and outside of the United States. Really a great year that's coming. We are enormously proud of the approval of WAINUA right at the end of the year, on December 21st, for a severe rare genetic disease called hereditary TTR polyneuropathy.
This was a medicine that was conceived, discovered, and developed at Ionis, and now, for the first time in our history, we will participate in the delivery of a medicine directly to patients' commercialization in our first-ever co-commercialization partnership, which is with AstraZeneca. There are several very important first-time achievements for this approval that go in addition to the approval itself of WAINUA. The first is, this is the first approval for a chemical platform, a drug discovery platform that we refer to as LICA for Ionis with an excellent efficacy profile and a very clean safety profile, which not only bodes extremely well for the success of WAINUA, but it bodes very well for the rest of our LICA platform pipeline, that in which we have several drugs phase III development and in phase II development.
As I said, it's also the first time we will be participating in the delivery of a medicine that we conceive, discover, and develop directly to patients in our co-commercialization agreement. Honestly, I have to say, it feels darn good for the first time in our rich history to have the Ionis name and brand on the label and on the packaging... But what matters most, of course, is delivering WAINUA to the patients that are looking for a treatment like this, for this severe disease, TTR polyneuropathy. We believe we are well-positioned to potentially be the treatment of choice, for TTR polyneuropathy for several reasons. The first, of course, is a strong, strong clinical profile.
We achieved robust target engagement in our clinical trials, and we also demonstrated halting and reversal of disease that was sustained at week 35, week 66, and at week 85 throughout the study. In addition, we are well-positioned to deliver WAINUA around in the United States first and then around the globe to reach as many patients for this severe debilitating disease as possible in our co-commercialization partnership with AstraZeneca. Both companies bring enormous capabilities to achieve exactly that. Ionis is a leader in TTR amyloidosis.
We have been for over a decade now, and we will be playing a key role in taking advantage of those capabilities to deliver and be responsible for many functional areas in the co-commercialization agreement, including the leading patient services. And of course, being able to take advantage of and utilizing the global commercial reach of AstraZeneca to reach as many patients as possible in the United States and then around the globe, will also allow us to reach and be successful in this market. And then finally, our administration profile is a very significant advantage.
Not only do we have great efficacy with a clean safety profile, we are the only silencer that's on the market today in which patients can self-administer themselves at home or wherever they want to be using a simple, painless auto-injector infrequently, once per month. In addition, the WAINUA approval lends even greater confidence in a much larger patient population, the ATTR cardiomyopathy patient population, which is phase III study that's fully enrolled and ongoing. This is a landmark trial called CARDIO-TTRansform. As I said, it was fully enrolled last year, and it is positioned to deliver the richest data set of any treatment for this indication as early as next year. And again, the approval of WAINUA really does, for polyneuropathy, really does set us up very nicely for this really large patient population.
Right behind WAINUA are an additional two, specifically, near-term commercial opportunities that are rapidly approaching. Both of which represent the first independent commercial launches for Ionis. Olezarsen, our treatment in late-stage development for the management of diseases related to severely elevated triglycerides, is in phase III development for a rare genetic form of this disease called FCS, and is also in phase III development for a much larger prevalent patient population called SHTG. Donidalorsen is also in late-stage development. This is a prophylactic treatment for a rare genetic disease, hereditary angioedema. And then right behind these near-term commercial launches, following WAINUA, is the next wave of LICA medicines that are gonna largely be driven by our industry-leading neurology platform. But first, let me say a few words about Olezarsen and Donidalorsen, starting with Olezarsen.
We could not have been more pleased with phase III data we reported in September of last year for Olezarsen in patients with a genetic cause of severe hypertriglyceridemia called FCS. Not only did we achieve robust, greater than 80% reductions in ApoC3, our target in this study, we achieved statistically significant and robust reductions in triglycerides, the primary endpoint in this study, in the BALANCE study. But what was really remarkable is that we were able to statistically significantly lower and robustly lower an outcome measurement of acute pancreatitis in this study. This is what patients fear the most with severely elevated triglycerides. They're at risk for a potentially fatal acute pancreatitis attack.
We were actually able to show for the first time anyone has ever shown that a pharmacological lowering of triglycerides can actually reduce the risk of acute pancreatitis, all with a favorable safety and tolerability profile. So based on these, these great results, we are preparing our dossier to file the NDA for FCS very soon. And assuming we achieve priority, priority review, as a reminder, there are no treatments for FCS in the United States today. If we achieve priority review, this would be an approval by the end of the year and would represent our first independent commercial launch. And then right behind FCS is the much more prevalent SHTG population that we're pursuing. phase III trial is enrolling well.
There are more than 3 million people with SHTG in the United States alone, who suffer from the same things that FCS patients from. Not only comorbidity, all kinds of comorbidities, but they're at risk for a potentially fatal acute pancreatitis event. We're about to complete enrollment in phase III trial for SHTG, and we look forward to data next year from this trial. Right behind WAINUA, right behind Olezarsen is Donidalorsen, our late-stage treatment for... As a prophylactic treatment for hereditary angioedema. Patients are desperately looking for better treatment options for this potentially fatal severe genetic rare disease caused by unpredictable swelling that can be fatal, as I said.
Donidalorsen has the potential to meet all the needs that patients are looking for, for better prophylactic treatments, better efficacy, with the possibility of being attack-free, maybe even for the rest of their lives. Better tolerability, and better simplicity of the way they administer their treatment, and more convenience. And as I said, Donidalorsen has the potential to check every one of those boxes. We are looking forward phase III data from phase III trial, OASIS, this quarter. And we're also looking forward to presenting additional data on Donidalorsen in hereditary angioedema, phase III open label extension data later this year.
I can tell you that the vast majority of patients who entered the OASIS phase II trial completed the phase II trial and elected to roll over into the open label extension. That's a good sign. In addition, we're planning to share data from what we call the Switch study for Donidalorsen. This is the first time anyone has ever conducted a clinical trial like this, in which patients who are on other prophylactic treatments for HAE were actually invited to enter a clinical trial for Donidalorsen and switch their treatment from one treatment, from their existing prophylactic to Donidalorsen. We are very impressed with how quickly this study enrolled. And we're also impressed with how much people are staying on the treatment and wanting to stay on the treatment, which obviously is also good news.
And in fact, the news was. It was so it caught our eye so much that we actually have now expanded the Switch study to add more patients and to extend the treatment for these patients. Following Wainua, Olezarsen and Donidalorsen is the next wave of wholly owned medicines that we're planning to bring phase III and to the market. Largely gonna be driven from our industry-leading neurology pipeline. As you all know, the unmet need in for better treatments for neurodegenerative and neurodevelopmental diseases is vast, right? We have a leading, and not just a leading, a proven platform for delivering transformational medicines for neurological diseases, with three approved products now, two of which address central nervous system diseases. SPINRAZA, for spinal muscular atrophy, continues to be the treatment of choice for SMA.
And then just last year, we had QALSODY approved, the only approved medicine for a genetic cause of ALS. Right behind these three medicines is a deep pipeline of 11 medicines in clinical trials today, from phase II phase III, for broad indications like Alzheimer's and Parkinson's, to rare genetic diseases like ALS and Alexander disease, six of which we anticipate will be wholly owned by the end of this year by Ionis. This is a vast area, neurology, and we are focused on creating efficiencies and synergies by focusing on specific areas of neurology to maximize success, to build synergies, as I said. And the three areas we're focused on today are in rare pediatric neurology and in dementia.
In rare pediatric neurology, we already have phase III program for a disease, a severe fatal leukodystrophy called Alexander disease. We're planning to start two other additional clinical trials this year in pediatric neurology. One for a disease called PMD, another fatal rare leukodystrophy, and for MECP2 duplication syndrome. Then secondly, in for dementia, we already initiated our clinical program for prion disease, and we're anticipating to start a new clinical trial, another clinical trial, for a new drug, a new target for dementia, for a large patient population, actually, by the end of this year. Then coming behind pediatric neuro and dementia, will be the next wave of neurological diseases we plan on penetrating, including neuromuscular and peripheral, neuromuscular diseases and peripheral neuropathies, as well as motor diseases.
And they're not far, that far down the road before we start moving into those areas. In addition to making great progress against our corporate, our strategic objectives of building the wholly owned pipeline and delivering our medicines ourselves, we're also making great progress in our third strategic objective: to expand and diversify our technological drug discovery capabilities, to further extend our leadership position in oligonucleotide therapeutics. And we're doing that, shown here on this slide, by increasing the range, the capabilities, for drug discovery, and we're already there. We have new backbone chemistries for antisense oligonucleotides that are in development today, that are extending durability to allow for semiannual, potentially annual dosing.
We have our first Ionis derived chemistries for siRNAs that'll hit the clinic this year as well, and we're making great progress in gene editing as well. We're also making great progress in optimizing delivery for the technological advancements and investments we have made over the last few years, including opening up tissues and cell types that have historically been recalcitrant to uptake of oligonucleotides, such as cardiac myocytes and skeletal muscle. And in fact, we've moved our first cardiac myocyte targeting targeted delivery molecule into development late last year. And we're making great progress in traversing the blood-brain barrier, using targeted delivery approaches to further to allow us to be able to treat CNS diseases with subcutaneous administration, further extending our leadership position in neurological diseases.
All of this is focused on expanding our therapeutic opportunities for both existing franchises as well as creating new ones, such as in pulmonary diseases and in renal diseases. So 2024 is set up to be another great year, just like 2023 was, with many key value-driving events that are anticipated, including phase III clinical data events that are—that's highlighted by this quarter, the phase III results for Donidalorsen in hereditary angioedema. Several mid-stage pipeline readouts, any which ones of which the, if the positive, would advance into phase III development. Many regulatory actions, including the potential approval of Olezarsen in FCS late this year, and new product launches. WAINUA for TTR polyneuropathy in the United States, Olezarsen for FCS in the United States, and then QALSODY for SOD1-ALS outside of the United States.
We are laser-focused on achieving all of these objectives, but we're also laser-focused on continuing to produce great data and data on time from our rich phase III pipeline. This time last year at the JPMorgan conference, I presented a pipeline that had six medicines for eight disease indications in phase III development. Today, I'm presenting you with a pipeline of nine medicines for 11 disease indications in phase III development for both large indications and severe rare indications, setting us up for a steady cadence of phase III data readouts this year, next year, and for many years to come.
All of this sets us up to achieve our vision to deliver a steady cadence of transformational medicines to patients, to the market in the near term, in the midterm, and sustainably into the long term, as shown on this slide, both from our wholly owned pipeline, shown in purple, and from our partnered pipeline as well. So, to conclude, we are well positioned to drive next-level value at Ionis. We're making tremendous achievements. The progress we're making is, you know, truly remarkable across the business, and we're doing so and will continue to do so by focusing on our wholly owned pipeline. To deliver our medicines directly to patients ourselves, through our commercial capabilities, which are now in place.
To expand and diversify our technological capabilities for drug discovery, and to continue to strengthen and utilize our strong financial position to be able to make all the investments we need to make to drive next level of value for all stakeholders. Now, before finishing, I'd just like to say a couple of words. The progress and the achievements we made at our Ionis, really over the last couple of years, especially last year, and setting us up for this year, have truly been remarkable. However, none of this would have been possible without the outstanding and deep collaborations with scientists and clinical investigators around the globe.
None of this would be possible without the participation of patients and families who support our programs and participate in our clinical trials like the ones you see on this slide. And finally, and equally important, is that none of this would be possible without the dedication, perseverance, and commitment of the Ionis employees, 1,000 strong, who work around the clock to deliver these medicines to patients and to deliver better futures for patients around the world. Thank you.
Great. Thanks for the presentation. So maybe we can start with eplontersen or now-
WAINUA
WAINUA. Heading into this launch in ATTR polyneuropathy, can you just expand on the commercial strategy?
Yeah. So for polyneuropathy, the prevalence is estimated to be about 40,000 people around the globe. Most of these patients actually have what we refer to as a mixed phenotype, so they have a heavy cardiac involvement, cardiomyopathy, as well as polyneuropathy. What's striking is that the vast majority, more than 80% of these patients, are actually not on treatment today, right? So this isn't a switch market. This is actually a market or an area, a disease, that needs to be developed, right? A market that needs to be developed. And we have to go out and find those patients and deliver WAINUA to those patients.
We have good strategies in place, along with AstraZeneca, to go global and to find these patients, and to deliver WAINUA. It's really a market that needs to be developed. It's not a switch market, like you said.
Maybe thinking about the U.S., can you talk a little bit about how you and AstraZeneca intend to navigate the expected difference in out-of-pocket costs for patients, in Part D, relative to your competitor in Part B?
Yeah. Part B versus Part D drugs. You know, for many years, this has been an uneven playing field and really an unfair situation for patients who have significant out-of-pocket expenses for self-administered drugs versus drugs that are administered by a healthcare provider. And of course, as you said, this is a U.S. market thing, and it's also only for Medicare patients. What we know is that a small portion of patients with TTR polyneuropathy are actually on Medicare, so the vast majority are actually in commercial. What we also know is that the Inflation Reduction Act is now leveling the playing field and really evening the playing field, if you will.
The out-of-pocket expenses have greatly been reduced starting this year as the IRA kicks in to normalize, if you will, out-of-pocket expenses for patients on self-administered Part D drugs, and then it's going to go down further next year. So we think that unfair disadvantage for patients who want to be able to control their own disease and administer treatments themselves and not have to go to a healthcare provider is coming to an end, quite honestly. So we're very pleased about that, and we think that's what's best for patients.
Great. So if that's part of the U.S. commercial landscape, can you maybe compare and contrast the commercial landscape outside the U.S. in ATTR polyneuropathy?
Yeah. I think the biggest differences for patients that are outside the U.S. versus inside the U.S., I think, I guess there's a few. One is that most patients outside the U.S. are treated actually by centers of excellence, rare disease centers. They get assigned to those centers, so you'll see them concentrated in those centers of excellence, if you will. The second is that it's more endemic to specific geographies outside the U.S., Sweden, Portugal, Brazil, Japan, high concentrations of patients with TTR polyneuropathy. It's much more uniformly distributed in the United States. And you see a lot more treatment in the United States outside of centers of excellence in rural communities and so forth.
I guess the third thing is that there's a treatment that is on the market outside the U.S. that's not on the market in the U.S. It was not approved in the United States. That's Tafamidis, which is approved for ATTR cardiomyopathy. It's also approved in certain geographies outside the U.S. for TTR polyneuropathy, and I think it's only for stage one disease, too, so a small segment. It did not have a phase III readout in polyneuropathy, that's why it wasn't approved. But I think those are pretty much the main differences as I see it.
So you mentioned cardiomyopathy, and we've got the first outcomes readout for TTR silencer coming up in the next several months here. Can you talk about key differences between your CARDIO-TTRansform trial and the HELIOS-B trial?
Well, what we know, I mean, focusing on our trial, is that we have. We strongly believe, as does our partner, AstraZeneca, that we have the right trial design for this large patient population, the CARDIO-TTRansform study. It's the largest, so that's a differentiator, by far. The largest study ever conducted in this patient population. Why is that important? Well, that's important because all contemporary programs, clinical programs that are developing new treatments for ATTR cardiomyopathy, were powered originally based on powering assumptions derived from the Tafamidis ATTR‑ACT study that was done nearly a decade ago. At that time, patients were being diagnosed way late, and as a consequence, they were succumbing to their disease very quickly.
Well, thanks to better disease awareness and better methodologies for diagnosing this disease, patients are being diagnosed much earlier, and they're living longer. So, that's okay, but you need to do bigger studies to get the risk reduction in cardiovascular outcome that you need to show to have a viable product. And that's what we have. We have the largest study ever conducted, which increases the probability for a successful outcome, period, and also will provide the richest data set ever conducted in this landmark trial, allowing us to be able to look at subgroups such as how does WAINUA provide value on top of Tafamidis? How does WAINUA derive, produce cardiovascular value for cardiovascular disease as a, as a monotherapy? Hereditary patients versus the wild-type patient population and so forth.
So I think the biggest difference is really the fact that we have a landmark, the largest study ever conducted, which is poised to produce the richest data set ever in this therapeutic area.
You've talked about the potential for data from that trial as early as the first half of 2025. What are the conditions that would trigger the earlier readout, and when should we expect the study to complete if it's not stopped early?
Right. So this is a study with more than 1,400 patients. The full study treatment is for 140 weeks, if it were to play out to the very end, finish line. This is a trial that's time-based, but it's also event-based, right? We can complete - we will complete this study, if our blinded event rates, cardiovascular mortality and hospitalizations, reaches a range, such that is in the range that we designed the study based on, we powered the study based on. So once we reach that range, we can end the study. And I can tell you that this truly is a severe disease. The events are incredibly frequent and remarkable, and we're really seeing a hockey stick in the accumulation of events in the study.
Of course, we'll also look at other, you know, environmental things that are out there and if we see anything that suggests that the effect size of a silencer in this disease population is far greater than what we originally assumed when we powered the study, which could also lend an earlier readout. If the study were to play out to the finish line, 140 weeks, 1,400 patients, that would bring us to sometime in 2026. I have to say though, you know, we will not compromise the quality of the data, the depth, you know, the richness of the data that we're expecting to have to read out early. This is, this is, we're playing the long game here.
This is a large unmet medical need, and we're positioned to have the richest data set, and we're not gonna compromise the quality of the data to get to, you know, completing the study, you know, by a minimal amount of time earlier. It's just not worth it.
So with all this in mind, how would you characterize your confidence in the success of that study?
It went up enormously with the approval of WAINUA for TTR polyneuropathy. You know, that phase III trial lends great confidence because we're seeing robust TTR reductions, greater than 80% in the trial, with excellent safety, tolerability, compliance. That certainly feeds in well. Our confidence also went up from the WAINUA phase III trial, because we also saw signs in the mixed phenotype patients, the patients that had both neuropathy and cardiomyopathy, that they were doing better. We're seeing improved, you know, reduced amyloid burden in the heart of the, in the cardiac tissue of these patients, as determined by MRI and echo, echocardiographic analysis. We're seeing improvements in functional endpoints, ejection fraction as well. It's anecdotal. It's small numbers of patients, but it's also lends greater confidence.
I mean, TTR is the cause of this disease, and we're blocking the production of the cause of ATTR cardiomyopathy. So, nothing's proven until it's done, but our confidence certainly has gone way up with the recent developments of WAINUA (eplontersen) in TTR polyneuropathy.
Great. And I guess, assuming success, how do you think about where eplontersen would be used in aATTR cardiomyopathy? Just thinking about the context of-
Mm-hmm.
Tafamidis in the market, eventual Tafamidis generics and so on.
Yeah. We and our partner, AstraZeneca, have done extensive market research with payers and with physicians, cardiologists that treat these patients. It's clear that this disease is not met by current this current stabilizer that's on the market, Tafamidis. Patients are still progressing with their disease. They need additional treatments on top of Tafamidis. And it's not just the opinions of physicians, cardiologists. It's also the physicians of payers. They are not gonna stand in the way of the cardiologists who say, "My patient needs better treatments." That's all. That's the conclusion of all the extensive market research we did. Tafamidis is a well-tolerated treatment.
So for patients that are on Tafamidis today, we see silencers going on top of that to add, to provide added benefit to those patients in their heart failure. For newly diagnosed patients, or for geographies where Tafamidis is not readily available today, there's no reason why, if the study supports it and is successful, that a silencer wouldn't be treated right up front, and there may not even be a need for a stabilizer if we get the efficacy that we're anticipating we're gonna get in this trial. So it's a dynamic population, and I see combination use with stabilizers, but then I also see eventual evolution to silencers being used, maybe independent of stabilizers.
Great. Maybe we can switch and talk about Olezarsen. Very impressive data that you've generated in FCS. How should we think about the launch in that setting and then the eventual launch in SHTG?
Yeah. Yeah, we too are very excited about phase III results in FCS, as I highlighted in my presentation. We're gonna be filing soon, as I said, with a potential approval in FCS. This is an ultra-rare indication for FCS, the genetic cause of severely elevated triglycerides. And we will launch in FCS at the end of the year, assuming priority review. And then we'll, you know, eagerly await the results of phase III trial next year in SHTG, the much larger patient population. We're about to complete enrollment in the phase III trials. We're gonna get into the market and start getting our...
This is our first independent commercial launch, so we're gonna be getting our teams in place to deliver medicines directly to patients by the Ionis commercial organization, patients suffering with this disease. And it's also gonna allow us to really build a market and educate people on the need for better treatment options for SHTG. It's kind of priming the market, if you will, the way I think about it, for the much larger prevalent SHTG market opportunity, which again, there's millions of people in the United States. So then, turning attention to SHTG, there's a whole host of endocrinologists and preventive cardiologists today that are eagerly awaiting a treatment for, like, Olezarsen for SHTG.
They understand the guidelines, both endocrine and cardiovascular, AHA guidelines, that clearly state that if your patients have triglycerides above 500, many of our patients in our trial are above 1,000, you need to do your best to get the triglycerides down, to get them out of harm's way for acute pancreatitis, right? These physicians are eagerly awaiting, as I said. We refer to these patients as the early adopters. They're sold on it. They're waiting. These will be the first wave of early adopters, aggressive treaters, if you will, that'll be that we'll be focusing on to really... This is a sizable, you know, maybe a third of that patient population in the United States that I referred to, that'll be affected by these early treaters.
That's the start. And then comes the next wave, which is disease education, market development. We're gonna be first to market by far in this patient population. So our job is to develop that market and expand beyond those early adopters to train, educate, to reach as many patients as possible in the U.S. and as well as globally.
On the SHTG trials, I thought prior timing had suggested those could read out as soon as, like, late 2024. Anything to make of the timing change there to data in 2025?
We lost about a quarter. It was just enrollment. So, you know, we expect to complete enrollment. We were gonna complete enrollment in the fourth quarter of 2024. We'll complete enrollment this quarter, I suspect. It's just getting the patients into the trial, getting new sites activated. We're running phase III trials, right? Because this is a large patient population. The pivotal trial and the confirmatory trial, they're identical. And many of the same sites in the two trials overlap with each other. So, you know, you gotta get one trial enrolled before you can get the other one enrolled. And then we start opening up new sites, which just take time to get the second confirmatory study enrolled. So nothing to be alarmed about.
We lost a few weeks, and we'll get that enrolled by, I suspect, this quarter.
Great. And maybe before we run out of time, I did wanna ask about Donidalorsen, ahead of phase III data. What do you wanna see in that data set in terms of the clinical profile?
Yeah. So what we're looking for, of course, in the phase III trial is, you know, competitive, clinically meaningful, highly statistically significant reduction in HAE attacks, in the treated patient population, compared to, placebo, as well as some of their baseline entry values in that study, right? We had remarkable phase II data, that showed substantial reductions in HAE attacks. We also recognize the fact phase III data does not always replicate phase II data. Sometimes the efficacy will come back a little bit. We'll see about that. But what we're looking for is a competitive profile with respect to efficacy for both, for two treatment arms. The monthly treatment arm, as well as statistically significant, reductions in HAE attacks in patients treated every two months.
We have both arms in the trial. If we have competitive efficacy, we then can take great advantage of our other advantages, right? Excellent tolerability, simplicity of an auto-injector, self-administered by the patient themselves, and the convenience of once per month self-administration, or even once every two months self-administration. So that's really what we're looking for in this study. And I also think it's worth highlighting again, the great results we're getting in, you know, the great program we have in our switch study for Donidalorsen, in which we're seeing very encouraging enthusiasm by patients coming off of existing prophylactic treatments. Eager to come into our switch study and go on to Donidalorsen, and continue on to Donidalorsen.
That data, too, will be very important for us to publish and be able to do two things. First, it validates our market research that patients want to switch or are willing to switch. They're looking for better treatment options, right? I think we've validated that now with the rate at which this study has enrolled. The second is that we will have the data to be able to inform allergists, immunologists, who treat these patients and be able to tell them: How do you switch a patient safely? We'll actually have the data to show that it's well-tolerated, but also more importantly, you can switch these patients without risk of HAE attacks. There's no gaps in coverage going forward.
I think that that's gonna be, you know, really important data, too, even though it's not part of the pivotal program.
Great. Well, we're out of time, so we will leave it there. Thank you.
Thanks, Jess.