Hello, and welcome to Ionis' Conference Call to discuss donidalorsen phase III results. 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, sir.
Thank you, Rocco. Hello, and thank you for joining us today to discuss the phase III results of donidalorsen in patients with hereditary angioedema, or HAE, that will be presented today at the European Academy of Allergy and Clinical Immunology Congress, or EAACI. Before we begin, I encourage everyone to go to the investor section of the Ionis website to view the press release we issued earlier today and the slides accompanying today's webcast. We will also post the EAACI presentations after they are presented later today. I would first like to draw your attention to slide two, which contains our forward-looking statement. 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.
Joining me on today's webcast are Brett Monia, Chief Executive Officer, who will start us off with some opening remarks. Eugene Schneider, Chief Clinical Development Officer, who will discuss hereditary angioedema and our donidalorsen development program. Kyle Jenne, Chief Global Project Strategy Officer, who will provide an update on our preparations to deliver donidalorsen to people with HAE. And Jonathan Birchall, Chief Commercial Officer, will join us for the Q&A portion of the call. And we are pleased to be joined by Dr. Marc Riedl, Clinical Director of the U.S. HAEA Angioedema Center and Clinical Service Chief, Division of Allergy and Immunology at the University of California, San Diego. Dr. Riedl is a preeminent leader in the field of hereditary angioedema and a principal investigator in the phase III OASIS-HAE study. He will present the OASIS+ Switch data later today at the EAACI Congress.
We are extremely pleased to have him present the donidalorsen data for you today. With that, I'll turn the call over to Brett.
Thanks, Wade, and thanks, everybody, for joining us to discuss the exciting and comprehensive phase III data evaluating donidalorsen for the treatment of hereditary angioedema, or HAE. As Wade said, we are very pleased to have Dr. Marc Riedl with us today to present these data and provide his key insights into their significance for people with this unpredicted and unpredictable and potentially life-threatening disease. So to get started, I'd like to begin by discussing the key role donidalorsen plays in our business strategy. The strategy is focused on creating great value, next-level value, by prioritizing our wholly owned pipeline, delivering our medicines directly to patients, and extending our technology leadership in oligonucleotide therapeutics. Ionis was founded on the principle of turning ground, groundbreaking science and technology into new transformational medicines. Donidalorsen is a testament to our scientific innovation.
It's a first-in-class RNA-targeted medicine that, if approved, could become a preferred prophylactic treatment for people with HAE. With the recent U.S. launch of our first Ionis co-branded medicine, WAINUA, along with the approval of QALSODY last year in the U.S. and now approved in Europe, the first and only medicine approved for a genetic cause of ALS, Ionis-discovered medicines are reaching even more people living with serious diseases. We're on the cusp of independently delivering a steady stream of new transformational medicines to patients, beginning with our planned launches of olezarsen and donidalorsen. Establishing our co-commercialization partnership with AstraZeneca for WAINUA, our novel treatment for hereditary ATTR polyneuropathy, was an important step, positionally preparing us for our upcoming independent launches. Following WAINUA, we expect to launch olezarsen, our medicine for patients with severely elevated triglycerides.
With our NDA submitted and assuming priority review, we anticipate approval by the end of this year for olezarsen. Based on the positive phase III data in familial chylomicronemia syndrome, or FCS, we expect olezarsen to make a profound difference in the lives of FCS patients and to be the standard of care. These data also further reinforce our confidence in olezarsen's potential for success in the much larger SHTG indication. With our phase III program now nearly fully enrolled, we're on track for SHTG phase III data late next year. After olezarsen is donidalorsen, our next anticipated medicine that we plan to bring to patients. Donidalorsen is an exciting opportunity for us, and the results that we're sharing today increase our confidence that, if approved, donidalorsen will advance the treatment paradigm for people with hereditary angioedema.
We have an efficient and scalable commercial organization in place for these and future commercial launches, and we're also establishing global access to our medicine for patients around the world, which includes our EU partner for donidalorsen, Otsuka. Our regulatory submissions for this program are right on track. We expect to submit our NDA in the second half of this year, positioning donidalorsen for approval in the U.S. next year. Additionally, Otsuka is preparing to file in the EU by the end of this year. Before I turn the call over to Eugene, I'd like to thank the patients, families, and clinicians who have participated in the OASIS-HAE and OASIS+ studies and contributed the very positive results we're reporting today. And with that, I'll pass the call over to Eugene.
Thank you, Brett. I'm pleased to share the positive and robust phase III results for donidalorsen. The breadth of the data speaks volumes. In the studies, donidalorsen treatment demonstrated that its benefit for HAE patients is substantial, durable, and consistent across multiple studies and measures. Most important for patients is that donidalorsen treatment translated into improved quality of life that patients reported throughout the different studies. The bottom line is we couldn't be more pleased with the results we're sharing with you today. Our robust data set includes data we have previously shared with you, including our placebo-controlled phase II study and ongoing phase II open label extension study or OLE. Now it also includes our phase III study, OASIS-HAE and OASIS+, which includes our phase III OLE cohort and our switch cohort. Donidalorsen treatment significantly reduced HAE attacks.
The reduction in attack rate translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high level of disease control in the vast majority of patients. Importantly, with longer-term treatment, patients got even better on all of these measures. These positive data were further bolstered by the very encouraging switch results. In the switch study, through week 17, patients showed a substantial reduction in their HAE attack rate with donidalorsen treatment compared to baseline. Donidalorsen treatment also resulted in improved quality of life measurements and increased disease control. And importantly, patient reported a strong preference for donidalorsen. In addition to its strong efficacy and favorable safety and tolerability profile demonstrated in these studies, donidalorsen offers the potential for simple, monthly, or every two months self-administration via an autoinjector.
And with this robust profile, we believe that donidalorsen is uniquely positioned to advance the prophylactic treatment paradigm for people with HAE, if approved. Now, let me provide some background on this disease and how donidalorsen is designed to prevent the severe attacks associated with it. HAE is a rare genetic disease that results in unpredictable, debilitating, and potentially life-threatening swelling attacks. HAE swelling is different than an anaphylactic or allergic reaction. A person with HAE wakes up each day not knowing if today will be an attack-free day or not. Inadequate C1 esterase inhibitor activity is at the center of this condition for nearly all people with HAE. This deficiency causes aberrant activation of the kinin kallikrein system, which in turn leads to elevated bradykinin levels. High bradykinin is ultimately responsible for opening up the blood vessels that release fluid, causing severe swelling.
Swelling can occur in various parts of the body, including the face, throat, and abdomen, which causes pain and can be life-threatening. When designing donidalorsen, we first looked at each step in the HAE disease pathology, and as part of this process, we found that targeting prekallikrein or PKK was a very attractive target for therapeutic intervention. By inhibiting PKK, a key factor in the HAE disease pathway, donidalorsen is specifically designed to prevent HAE attacks, and this is unique to donidalorsen, making it first-in-class RNA-targeted medicine in development for the prophylactic treatment of HAE. Here in these photos is what an attack could look like for someone living with HAE. As you can see from the severity of the swelling, preventing an attack in a person with HAE is key. The first image is the patient when she's fine, when she's not having an attack.
The second picture is of the same patient during a significant swelling attack, including swelling of her mouth, which indicates that she's probably having difficulty swallowing, which could potentially lead to her airway being compromised. In the last picture, the patient has now received acute treatment, and you can see that the swelling has started to come down. These HAE attacks can last for up to five days. If this patient or the treating doctor did not know the swelling was due to an HAE attack, this attack may have gotten even worse. HAE attacks can be mistaken for an allergic reaction or other condition leading to misdiagnosis. The goal for these patients is in preventing an attack or, at a minimum, reducing the severity of an attack with a prophylactic treatment.
HAE occurs in approximately 1 in 50,000 people around the world, with an estimated 20,000 people affected in the U.S. and Europe. It is a genetic disease, so it runs in families. However, approximately 25% of patients diagnosed do not have a family history, which means that it may take years before a patient has a correct diagnosis and can get on treatment. People with HAE usually have their first attack as a child, with about 50% experiencing their first attack before their 10th birthday, and the majority before they turn 18. So this is a disease that people with HAE have to manage for nearly all of their lives. HAE swelling attacks can greatly impact patients' lives, making people miss work or school for days at a time.
The majority of patients have had to go to the emergency room for treatment, with 16% reporting that they had inappropriate surgery as a result of being misdiagnosed. 16%! Here's an overview of our robust phase III development program for donidalorsen. In a moment, Dr. Riedl will walk you through the data from each of these studies, which are being presented today at the European Academy of Allergy and Clinical Immunology Congress. On the left is the phase III OASIS- HAE study, our pivotal study. OASIS- HAE evaluated an 80-milligram dose in two dosing frequencies: Q4- week or monthly, and Q8-week or every two months. The results demonstrated robust reductions in PKK and HAE attacks, improved measures of quality of life, and favorable safety and tolerability, with donidalorsen treatment in both 4-week and 8-week dosing options. On the right side of the slide is the OASIS+.
This study includes the open label extension cohort, or OLE cohort, for patients rolling over from the phase III pivotal study and a switch cohort that we refer to as the switch study. Our switch study is first of its kind prospective study to include the specific protocol that patients followed when switching from their prior prophylactic HAE medication to donidalorsen. The data generated to date from the OLE are very exciting and demonstrate durable efficacy of donidalorsen, with even greater improvement with longer-term treatment. Additionally, patients who switched to donidalorsen from other prophylactic treatments saw a further reduction in HAE attack rates and improvement in disease control compared to baseline, and also reported a strong preference for donidalorsen. We're very pleased with the positive results from the comprehensive phase III development program for donidalorsen. [They] will be presented later today in three separate late breaker presentations at EAACI.
We're preparing to submit an NDA in the United States, putting us on track for a potential approval and launch next year. Our European partner, Otsuka, is also preparing to file for marketing approval in the E.U. later this year. Our submission will include the data from OASIS and OASIS+, including our OLE and Switch data, as well as the data from our phase II placebo-controlled study. As a reminder, donidalorsen was granted orphan drug designations in the U.S. and E.U. for HAE. Here now to present the phase III donidalorsen program results is one of the academic leaders in the field of allergy and immunology, who also cares for people with HAE on a daily basis, Dr. Marc Riedl. Dr. Riedl?
Thank you, Eugene. It's good to be here, and here's my disclosures related to the presentation. OASIS-HAE is a global randomized placebo-controlled study that enrolled 91 patients with either type 1 or type 2 HAE. These patients were randomized to either 80 milligrams of donidalorsen or placebo, administered every four weeks or every eight weeks by subQ injection for 24 weeks. The primary efficacy endpoint in OASIS-HAE was time-normalized HAE attack rate over weeks 1- 25. At the end of treatment, patients had the option to roll over into the open-label extension study. The key secondary endpoint in the study was time-normalized HAE attack rate over weeks 5- 25. The study also included multiple other secondary and exploratory endpoints, including number of HAE attacks requiring acute therapy, severity of attacks, multiple quality of life measures, and emergency room visits. Here's the patient's disposition.
91% of randomized patients completed this study, and 94% of eligible patients opted to continue donidalorsen treatment or, for placebo patients, initiate treatment in the ongoing open-label extension study. The study included seven adolescent patients, and none of these patients were randomized to placebo. It was comprised of mostly type 1 patients, which is reflective of disease epidemiology, and the patients who were randomized to the donidalorsen treatment groups had a higher disease burden, with more attacks in the year before entering the study and a higher HAE attack rate during the run-in period. Donidalorsen treatment resulted in substantial and sustained reductions in HAE attacks. At the Q4-week dose, donidalorsen demonstrated a mean reduction of 87% compared to placebo from weeks 5-25.
And since peak prekallikrein knockdown is reached by the second dose, weeks 5-25 were slightly higher than weeks 1-25, which demonstrated an 81% reduction in HAE attacks compared to placebo at the Q4-week dose. Both time periods were statistically significant. Additionally, as you can see from the orange line, by week 21, the Q8 week dose demonstrated similar HAE attack rate reduction as the Q4-week dose. It just takes a bit more time to get there. Both the Q4-week and the Q8 week dose groups also resulted in substantial reductions in the severity of HAE attacks. And as you'll see, this is also reflected in the improved quality of life measurements, which I'll present in a moment.
Additionally, the use of acute HAE treatments declined substantially with both dosing frequencies, with the Q4-week dose providing the largest reduction in rescue treatment. Here you can see the percentage of donidalorsen patients that had a reduction in HAE attack rates from baseline over weeks 5- 25. With at least 70% reduction in HAE attack rate, both dosing frequencies were statistically significant. Additionally, nearly all donidalorsen patients achieved more than a 50% reduction in attacks, and more than half in the Q4-week dose group were attack-free during the study. Here are the results from the Angioedema Quality of Life questionnaire, or AE-QoL, which is a validated tool that measures the quality of life of a patient, taking into account several domains, including functioning, fatigue and mood, fear and shame, and nutrition.
As Eugene discussed, HAE can negatively impact the quality of life for people with HAE, and this tool helps measure the impact in specific areas. For example, functioning includes a person's ability to work and enjoy social relationships, and fear and shame includes the patient's fear of sudden swelling and the overall burden of having swellings, among other metrics. An improvement of 6 points in the AE-QoL is considered clinically significant. This quality of life score significantly improved with treatment in both dosing groups. Donidalorsen improved quality of life by 25 points in the Q4-week dosing group and by 20 points in the Q8 week dosing group. Both of these changes represent a significant improvement for patients, and numerical improvements were observed for each domain compared to baseline.
The positive impact on patients' quality of life was further reinforced by the results from the validated angioedema control test, which assesses if a patient's disease symptoms are controlled—are considered well controlled. So you can see at baseline, most patients were not well controlled. At week 25, 91% in the Q4-week dosing group and 74.4% in the Q8 week dosing group were well controlled. To assess the impact to patients in the healthcare system, the number of ER visits were also tracked. Here again, donidalorsen treatment resulted in a substantial reduction of both all-cause and HAE-specific ER visits for patients of over 90% for both dose groups, demonstrating the potential for donidalorsen to profoundly improve the quality of life for HAE patients. Donidalorsen demonstrated a favorable safety and tolerability profile in both dose cohorts.
Overall, treatment-emergent adverse events, or TEAEs, were higher in the placebo group compared to the donidalorsen groups, and there were no serious TEAEs related to study drug. In summary, treatment with donidalorsen in the OASIS-HAE trial resulted in clinically meaningful benefits in patients with HAE, including substantially reduced HAE attack rates with both the Q4-week and Q8 week dose groups, improved quality of life measures, high levels of disease control, reduced ER visits and use of acute treatments, and donidalorsen was well tolerated with no safety concerns identified. Now let's get to the OASIS+ trial. I'll first start with the open-label extension cohort. Just as a reminder, the open-label extension was for those patients who chose to roll over from OASIS-HAE, of which 94% of the patients did.
For patients previously on Q8 week dosing in OASIS-HAE, they remained on Q8 week in the open-label extension, unless they had an attack in the last eight weeks of OASIS-HAE, in which case they were transitioned to Q4-week dosing. Aside from this change, patients maintained the same dosing frequency in the OLE, which includes a 53-week treatment period. All placebo patients from OASIS-HAE transitioned to Q4-week dosing in the open-label extension. 83 patients were dosed in the OLE study, and these data are as of the end of February. As of this data cutoff date, 98% of patients remained in the study, with the majority receiving Q4-week dosing, and treatment duration was up to more than 18 months.... Here's the reduction in HAE attacks. The first part of this graph, shaded in gray, shows OASIS-HAE results through week 25.
After week 25 is the OLE study, which shows substantial and sustained reduction in HAE attacks that continued to improve over time. In the OLE, you can see that both the Q4week and Q8week groups are demonstrating very similar efficacy with extended treatment. From baseline, the reduction in HAE attacks with donidalorsen treatment was 93% for the Q4week group and 92% for the Q8week group. These data demonstrate that longer donidalorsen treatment resulted in patients achieving a continued reduction in HAE attacks. As you would expect from the marked reduction in HAE attacks, patients reported further improvements in quality of life measures, including the Angioedema Quality of Life questionnaire. Patients also reported high levels of disease control. These are the two same instruments we discussed in the OASIS study results.
These data reinforce the potential that extended donidalorsen treatment can have an important positive impact on HAE patients. In the open label extension, donidalorsen continued to demonstrate a favorable safety and tolerability profile in both dose cohorts with long-term treatment. Now moving to the SWITCH study. The SWITCH study is an open label study in patients who were previously on other prophylactic treatments. Prior treatments included lanadelumab, berotralstat, and C1 esterase inhibitor. As part of the study protocol, patients followed a switch schedule based on their previous prophylactic treatment. This schedule was developed taking into account the estimated half-life of their prior treatments and the onset of action of donidalorsen. Here's the overall study design for SWITCH.
Criteria for enrollment was limited to patients at least 12 years old with HAE type one or type two, on stable dosages of prophylactic treatment with either lanadelumab, berotralstat, or C1 inhibitor for at least 12 weeks before they entered screening. No other criteria were used to enroll this study, limiting any potential bias. Patients were administered 80 milligrams of donidalorsen every four weeks. This study will last up to three years, and after the first year, patients may move to Q8 week dosing. There were three main objectives with the SWITCH study. First, to demonstrate how to switch to donidalorsen without loss of control or adverse events. Second, to evaluate the long-term efficacy and effects of donidalorsen. And third, to evaluate patient preference. These objectives were assessed with HAE attack rate data, as well as quality of life and disease control instruments.
For preference, study site personnel conducted an independently administered survey with patients. All of these assessments were completed at week 17. There were 64 patients dosed in the study, including four adolescents, with the majority previously on lanadelumab, which reflects current real-world market dynamics. As of the data cutoff, 89% of the patients completed 17 weeks of treatment, and 88% of patients remained in the study. SWITCH patients had a mean treatment period of approximately 8 months, with some completing just over a year of treatment as of the data cutoff. Here are the first of the SWITCH results. Patients switched from their prior prophylactic treatment to donidalorsen without an increase in their HAE attack rate. As you can see, patients' HAE attack rate declined substantially from baseline with donidalorsen treatment over 17 weeks in each of the dosing groups.
The total mean HAE attack rate reduction was 62% at week 17 compared to baseline. Now, here's more detailed data on HAE attack rates. At the bottom of the graph, baseline for patients was their attack rate during the screening period, which, as a reminder, was up to 10 weeks while on their prior prophylactic treatment. As a point of reference, the baseline attack rates in this study were similar to those reported in real-world settings. The bar graph shows the reduction in HAE attack rates with donidalorsen treatment at week 17 compared to baseline. As you can see, HAE attack rates for patients in each group continued to improve substantially over their baseline attack rates. Here's the preference data. In total, 84% of patients reported that they preferred donidalorsen over their prior treatment.
11% reported no preference, and 5% reported they preferred their prior treatment. Patients who preferred donidalorsen were also asked to provide a reason or reasons for their preference. As you can see from the data, patients indicated different preference reasons based on their prior treatment. Patients indicated that they appreciated the improved disease control, reduced time for administration, and decreased injection site pain or reactions with donidalorsen treatment. SWITCH patients also reported further improvements in quality of life measures, including improvements in the Angioedema Quality of Life questionnaire score. And as a reminder, an improvement in the AE-QoL score of six points is considered clinically meaningful. In addition, patients improved on the Angioedema Control Test, or the AECT, compared to baseline. With the AECT, while a sizable number of patients reported that their disease control...
Their disease was well controlled at baseline with a currently available prophylactic therapy. After 17 weeks of donidalorsen treatment, patients reported that their disease control increased substantially to 90% or more. The level of control achieved with donidalorsen treatment is consistent with the results seen in the placebo-controlled OASIS-HAE study, with Q4-week dosing and in the open-label extension with both dosing groups. Donidalorsen continued to demonstrate a favorable safety and tolerability profile in the SWITCH studies, consistent with what was observed in OASIS-HAE and in the open-label extension. So in summary, treatment with donidalorsen in the OASIS+ trial demonstrated beneficial outcomes for patients, including continued improvement for patients in all measures in the open-label extension with longer treatment, including HAE attack rates and quality of life measures. Additionally, patients reported high levels of disease control.
SWITCH study patients transitioned to donidalorsen without an increase in HAE attacks, and SWITCH patients also saw a further reduction in HAE attacks, improved quality of life measures, and disease control at week 17 compared to baseline, consistent with the results of OASIS and the OLE studies. 84% of patients preferred donidalorsen. All of this is combined with favorable safety and tolerability observed in the study. And with that, I'll turn the call back over to Eugene.
Thank you, Dr. Riedl. Today, there are several treatment options available for patients with HAE. Despite that, a significant need remains, and that is why I'm so excited at the potential that donidalorsen can offer to people living with HAE. As Dr. Riedl just discussed, we generated important data from the prospective SWITCH study, showing that donidalorsen treatment resulted in meaningful improvements for patients. Remember, these were patients already on prophylactic treatment at baseline. The SWITCH study showed that donidalorsen increased disease control to 90% or more, with patients well controlled at week 17, compared to an average of 67% at baseline. Additionally, treatment resulted in a 62% mean improvement in patients' HAE attack rate, and importantly, more than 80% of patients preferred donidalorsen. We're pleased with the robust and highly positive data generated for donidalorsen.
What stands out to me is how the data from OASIS, OASIS+ OLE, SWITCH, and the phase II study all tell a consistent and encouraging story. Patients in these studies are able to substantially reduce or potentially eliminate their HAE attacks and dramatically improve their quality of life. 90% or more of patients were well controlled, and all of this was on a sustained basis. Additionally, donidalorsen represents our third ligand conjugated antisense medicine, or LICA, to demonstrate a favorable safety and tolerability profile in a phase III study setting. Of course, with results like these, SWITCH patients overwhelmingly indicated that they preferred donidalorsen over their prior prophylactic treatment.
With the simplicity of monthly or every two months, self-administration by an auto-injector, combined with a strong efficacy and favorable safety and tolerability, we believe donidalorsen is poised to advance the prophylactic treatment paradigm for people with HAE. Importantly, with the SWITCH study results, patients and physicians, for the first time, now have data to inform switching from a prior prophylactic treatment to donidalorsen. With all of these positive data in hand, we're working to finalize our regulatory submission to the FDA. Our submission will include both monthly and every two months dosing options, as well as data from OASIS, OASIS+ OLE, SWITCH, and our placebo-controlled phase II study. We expect to submit our NDA in the near term, positioning donidalorsen for approval in the U.S. next year.
I would like to thank all of the people who have participated in our trials for donidalorsen, including the clinicians, patients, and families, some of whom have completed more than four years of treatment. We truly appreciate your commitment. With that, I will turn the call over to Kyle to discuss how we plan to bring this important medicine to people with HAE. Kyle?
Thank you, Eugene. Based on the excellent results we have seen in the extensive development program for donidalorsen, we're extremely pleased with what donidalorsen could mean for people with HAE. HAE is a well-defined patient population with an estimated 20,000 people affected in the U.S. and Europe. Within the U.S., prophylactic treatment is well accepted by patients and physicians, and as a result, the HAE prophylactic landscape is also well defined. Yet there continues to be a significant need, and the market continues to grow. Outside the U.S., acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe, which is a region of high growth. Assuming approval, we'll bring donidalorsen to patients in the U.S., and our partner, Otsuka, will bring it to patients in Europe.
Many people with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks, that also offers good tolerability and convenience. Remember, this is a disease that typically appears early in life, so patients have to manage their disease throughout most of their lives. As a result, patients have a history of switching treatments, seeking to find the best therapy for them. We know where the concentrated base of treating physicians are, and as a result, we're building an efficiently sized field team to reach prescribers and support the needs of patients. People with HAE tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability and administration profile. And this is supported by a recent survey that was conducted by the U.S. Hereditary Angioedema Association, the HAEA, in more than 500 people with HAE.
Of those surveyed, a majority reported using a prophylactic treatment in the last year. Additionally, many reported that they still have attacks, with 34% reporting that they had more than two attacks per month. So that tells us there continues to be a need, even with the current prophylactic treatments. Now, this is where we think donidalorsen could really fill patients' needs. If you recall, in all of our phase III studies, donidalorsen treatment resulted in 90% or more of patients being well controlled on the AECT with Q4-week dosing. That was 91% of patients in the OASIS-HAE placebo-controlled trial at week 9-week 25 , 91% of patients in the OLE, also at week 25, and 90% or more of patients in the switch study at week 17.
In the long-term OLE, which includes nearly all of patients from the phase III OASIS study, donidalorsen reduced HAE attacks by more than 90% at both the Q4-week dose and the Q8-week dose. With such a remaining need, it shouldn't come as a surprise that patients have an interest in new treatments. This is our market research conducted earlier this year. As you can see on the bar graphs, interest in new treatments is highest among those who are already on long-term prophylactic treatment. Nearly 9 out of 10 patients are interested in a new treatment. For those who are not on long-term prophylactic, in the U.S., that typically indicates that they have milder symptoms. However, more than half of this group of patients are also interested in new treatments.
With more than three out of four of all patients surveyed interested in a new prophylactic treatment, we believe there is a sizable group of patients waiting for a new therapy. So we know patients are interested in new treatments, but will they actually switch? Well, here are the data showing why we believe they will. four out of five patients in our market research reported that they have switched treatments before, with a large majority switching more than once. Patient switching was driven by three main criteria they're looking to improve in their treatment. They want improved efficacy and fewer attacks. If they have an attack, they want it to be less severe and less disruptive to their life, and they want improved convenience. Additionally, we know from our research that patients want a treatment that offers improved tolerability. We believe donidalorsen addresses each of these.
Based on data shared today, donidalorsen's strong efficacy and favorable safety and tolerability, combined with the simplicity of monthly or every two-month self-administration via an auto-injector, donidalorsen has the potential to advance the treatment paradigm for people with HAE. Today, I am pleased to say that we are right where we should be in preparing for donidalorsen to bring to people with HAE, our second planned independent launch as a fully integrated commercial organization after the upcoming olezarsen launch for FCS, assuming approval. Treatment selection is typically a shared decision between the patient and HCP. We know where treating physicians are, and it's a very concentrated prescriber base, with about 1,000 allergists and immunologists managing approximately 70% of HAE patients in the United States. As a result, we are building an efficiently sized team that will serve the needs of patients, HCPs, and payers.
And because we are planning to launch olezarsen in FCS, another rare disease, just before donidalorsen, we are able to leverage existing commercial capabilities for the donidalorsen launch. Based on the robust data generated to date, we believe donidalorsen is well-positioned to combine all of the attributes that people with HAE are looking for in a single attractive treatment. Donidalorsen offers a novel approach, strong efficacy, unique switch data, favorable safety and tolerability, and the simplicity of monthly or every two-month self-administration via an auto-injector. And with this, we believe donidalorsen could be a preferred prophylactic treatment for patients new to therapy and patients currently on available therapies. We have accomplished a lot to get us where we are today. We've generated robust, positive data and have the infrastructure in place in advance of our planned launch for this important medicine.
Now we have a very exciting year ahead of us as we get even closer to bringing donidalorsen to people with HAE. We look forward to submitting for regulatory review in the U.S. in the second half of this year, positioning us for approval next year. With that, I'll turn the call back over to Brett.
Thanks, Kyle. Donidalorsen represents an exciting and very important opportunity for Ionis. With the positive results from our extensive development program we reported today, we're confident that donidalorsen is positioned to advance the HAE treatment paradigm. Donidalorsen is not the only program driving positive momentum for Ionis this year. We expect additional approvals for WAINUA outside the U.S., approval of QALSODY in Europe, which has now happened, as well as approval of olezarsen for FCS , along with our first planned independent launch, assuming priority review and approval. We've arrived where we are today by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline, delivering medicines that we conceive , discover, and develop directly to patients.
Which establish Ionis as a leader in oligonucleotide therapeutics with several approved drugs and one of the richest mid- and late-stage pipelines in the industry. Our pipeline is delivering. We achieved multiple marketing approvals and positive key readouts over the past year and are poised to build on this strong momentum in the near term. We've prioritized building our wholly owned pipeline and have advanced new medicines into clinical development, with more to come this year. In parallel, our partner programs are progressing on track with important phase III readouts next year and beyond. We're extending our leadership position in oligonucleotide therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas, and opening up new ones for drug discovery. All of this sets us up to continue bringing a steady cadence of new medicines to patients for years and years to come.
With that, we'll now open the call up for questions. Rocco?
Yes, sir. If you would like to ask a question, please press star then one on your telephone keypad. If your question has already been addressed and you'd like to remove yourself from queue, please press star then two. Once again, ladies and gentlemen, that's star then one if you have a question. We'll pause for just a moment to assemble our roster. Today's first question comes from Myles Minter with William Blair. Please go ahead.
Hi, thanks for taking the questions. One for Dr. Riedl and one maybe for the company. Dr. Riedl, I was just wondering whether or not with the donidalorsen data in hand, like, you'd be convinced to put patients on dosing every two months instead of one month, which does look more efficacious from this data, in our view. If you would, I mean, what type of HA patient would you recommend for that extending dosing interval? And would you recommend maybe starting on once monthly and then switching to once every two months if those patients were well controlled? That's the first one. And then maybe for the company, we haven't really talked about CSL's garadacimab and the competitive profile against that.
I mean, how are you thinking about positioning against that product if that does receive approval by the end of the year? Thanks very much.
Yeah, so I can start. Happy to answer the question about treatments for patients. As you may know, I mean, HAE is such a variable condition, and so it really is sitting down with each patient and making that shared decision, discussing not only the multiple treatment options, but the potentially different doses of medicine. So I think while it's very hard to characterize a certain type of patient that you might prescribe a specific medication for, I would agree with you that based on the data we have in hand, that the Q four-week dosing looks to be perhaps more effective, at least in the short run.
And I think, you know, a rational strategy we may discuss with patients, if this is approved, is to start at that Q 4-week dosing and then potentially move out to Q8 -week dosing. That said, there are patients where the burden of treatment is very important to them, meaning that they're... it's important that they dose less often. And so, it's, you know, it's possible, depending on the labeling and indication with the approval, that one, you know, might, in certain instances, start with the Q8 -week dosing and see how patients do. So I think, I think it's very individualized to sort of encapsulate the answer, and it'd be something we'd have to discuss with patients based on the data we have in hand.
Thanks, Myles, for the question. Regarding your second question about the competitor program, listen, we're really thrilled with the overall profile for donidalorsen. The totality of this data really, really indicates to us, and everyone we've spoken with, that donidalorsen really has the potential to be the preferred prophylactic treatment for many, many HAE patients and whose existing treatments that are on the market today, as well as those that are emerging for all kinds of different reasons. You know, the competitive profile is really remarkable with respect to efficacy, with respect to the tolerability profile, with the potential for as the only prophylactic treatment on board for bimonthly dosing without the need for a loading dose.
When we take all this into account, we see, as I said, donidalorsen as a treatment of choice, potentially for many patients with HAE. I think I'll just leave it right there. Thanks, Myles.
Thanks for the questions. Congrats on the data.
Thank you. Our next question today comes from Gary Nachman with Raymond James. Please go ahead.
Hey, guys. Good morning. This is Dennis on for Gary. Thanks for taking our question, and congrats on the strong donidalorsen data. Just on the secondary endpoint you guys highlighted was the reduction in ER visits. Can you talk a bit more about the importance of this endpoint and how you think it'll help with commercialization, specifically from a payer standpoint? Thanks so much.
Thanks, Dennis. Kyle, please take that.
Yeah, Dennis, thanks for the question. This is Kyle. Very, very important data, obviously, in terms of, you know, 92% and 95% reduction in ER visits.
... this is telling us obviously that, donidalorsen is working as expected. It's, controlling attacks as, as would be needed, and, the profile of the drug is, is functioning the way that, that it should. In terms of the payer dynamic, this is really going to help us explain not only the efficacy side of things and tolerability and convenience of using the treatment, but obviously the cost dynamic and, the reduction of that. So overall, I think the totality of the data is really going to position us well, for payers and, establish reimbursement in a very favorable way.
That's very helpful. Thanks again, and congrats on the data.
Thank you. Our next question today comes from Yanan Zhu with Wells Fargo Securities. Please go ahead.
Great. Thanks for taking our questions. Congrats on the results. I have a question for the doctor and a question for the company. A question for the doc, for Dr. Riedl. With the data and with the switch studies results, what percentage of your current Takhzyro patients would you expect to initiate switching over, let's say, six months, a period of six months? And then the question for the company, there seems to be a substantial difference in the baseline HAE attack rates for the donidalorsen groups versus the placebo group. I'm wondering, how did that difference at baseline may have affected the attack reduction rates, or reduction in attack rate, attacks, in a, in a, on a primary endpoint? Thanks.
So to answer your question about the switch patients, I'll be honest, I'm notoriously bad at predicting what treatments patients will gravitate towards because of all the factors that go into that decision. And so I'm not going to be able to provide you an estimate on, you know, what percentage of a certain group may transition if and when donidalorsen is on the market. What I can tell you, what I think is interesting about the switch study is that, you know, clearly there are patients interested in additional therapies, as was pointed out during the presentation. And I think we don't actually know why patients enroll in specific trials. We don't know the reasons for their enrollment in the switch study.
But one possibility, of course, is that people are not entirely satisfied with their treatment that they're on. And so there were those patients in the switch study that were previously on lanadelumab. And so, while I can't give you a percentage, it suggests that there are people on any and all of the current therapies that are, you know, that are interested in something and another option, including potentially donidalorsen. So, I think there is interest. It's just very hard to predict, you know, what percentage of people will shift, to be totally honest.
Regarding the differential HAE attack rates at baseline for placebo and treatment groups, I'll take a stab at that, Yanan, and then ask Eugene to expand. So, yeah, it's a very important observation that you made, that we highlighted in the presentation. Patients seem to have milder disease that were in the placebo group versus the treatment group. So we had a higher uphill battle for the treatment group to show reductions in HAE attacks for both the four-week dosing as well as the every eight-week dosing group. The implications of that are probably that our HAE attack rates that we report for every four-week and every eight-week dosing are probably underestimates because these are placebo-corrected percentages that we provide.
Probably because of milder disease, there was a placebo effect. That if you look at the data carefully, that there was a 15%-20% reduction in HAE attacks in the phase III OASIS study that was not observed in the phase II study. And if you actually look at the HAE attacks for the every four-week dosing compared to baseline values for that same group, cohort group, it's exactly like the phase II data, which is 90% reduction in HAE attacks, which we think is really what's most... Which, which is we're also supported by the open-label extension data and all the other data that we've generated to date. Eugene, would you like to expand on anything I just said?
Not really much to expand other than to also, you know, you asked about the reason for this imbalance, if you will, and it's there. There could be several. One was the placebo arm was a little smaller or quite a bit smaller than the active arm, Q4 arm. And also the placebo arm happened to have a much higher proportion of male patients relative to the treated arms, which were more in line with what you see in general epidemiology of this disease. And it is also known that it is slightly milder phenotype in males, so that could explain potentially lower baseline attack rates in the placebo arm. But Brett already mentioned the implications of that.
Very, very helpful. Brett, just to maybe clarify, I think what this might have meant is that, had the-
... patients are on equal footing in terms of baseline, the number for the placebo adjusted attack rate could be even higher, if that's the right interpretation?
Oh, that's absolutely correct. That's, that's what I was stating, Yan, and it would probably be the 88%-90% range, had the placebo group been similar to the placebo group in the phase II study.
Got it. Very helpful. Thank you.
Thank you. And our next question comes from Jason Gerberry with Bank of America. Please go ahead.
Hey, guys. Thanks for taking my question. Do you see this survey indication on preference for Donny as a good indicator of a willingness to switch? And what sort of resistance do you think you'll face from physicians when it comes to switching a patient that's under control? And then, you know, just I didn't see a percent attack free rate, which I know is a metric of interest to some. I think Takhzyro was around 30%-40% at the two different dose levels for Q4-week, if I have that right. So just wondering how you stack up on that metric. Thanks.
Sure, Jason. You know, I'll start, and I'll get maybe a Dr. Riedl to provide his perspective. And then, Eugene, you can summarize us, for us the attack-free rate, because we didn't, we didn't report it in the presentation, but it was buried a bit. So we believe that the survey, the way the surveys were conducted prospectively and independently of the sponsor by the clinicians themselves or at the sites. Because it was very independent, we think it is a good reflection on what the real-world situation would be with respect to preferences for donidalorsen and reasons for patients wanting to switch to donidalorsen.
As we highlighted in the presentation, those reasons included better efficacy, better tolerability from the treatment they're currently on today, as well as the convenience, even monthly dosing. Our SWITCH study only had monthly dosing, so that could also even go up more with if we offer every two months of doses. We think it is a good analog. And also, it's also what our market research has told us, that patients want better efficacy, they want better convenience, and they want better tolerability. So really supported by the market research as well. Dr. Riedl, anything you'd like to add to that?
No, I think it's reflective of the real world, meaning that, I'll speak for myself, but I know colleagues who take care of a lot of HAE patients. When there are new therapies that come along, our general approach is to make sure patients are aware of those options. Options are good, in this condition, and so it's really going over what's new, what would that look like? And then, you know, discussing with the patient, are they satisfied with their current treatments, on efficacy, on tolerability, on interference with their life, the so-called burden of treatments. And if they're not, then we look at those new options and see whether there might be room to improve.
So, I do think the switch study sort of brings to the forefront some of the concerns at least some patients have with current treatments. That's not to say that, there certainly are people that are very satisfied with their current therapies, but there's some that that are looking to improve on some of those fronts that were mentioned. So, I also think the switch study is important because some of the angst that we have as specialists is if you're going to make a switch, are you going to cause problems during that switch process? Meaning, are people going to get sick when there's a transition? And this study sort of demonstrated a way that seems to prevent those sorts of problems.
So it's very useful data to have for us as clinicians, again, if and when donidalorsen is a treatment option.
Eugene, regarding attack-free rates, I believe the majority of patients were attack-free on the monthly dosage. Is that right?
Yeah. No, you, you got that right, Brett. It was 53%. It's, Jason, I refer you to the responder analysis bar graphs. We just- it's the very last bar graph on the right that has a threshold of 100%, basically 100% reduction from baseline. That's our attack free population. And so that result is in the slides.
Thank you. Our next question today comes from Joseph Stringer with Needham & Company. Please go ahead.
Hi, thanks for taking our questions. A question for Dr. Riedl, just on the HAE market. What, what percentage of the total prophylactic market do you anticipate, the injectables such as donidalorsen would capture, say, at steady state? Maybe another way of asking is, do, do you believe there will always be a segment of patients who are gonna prefer the oral option? For, for context, I think the current prophylactic market share of the orals, is close to 20%, and it's been, it's been growing. Maybe based on your experience in your patients, what do you think the split would be between the injectables and oral prophylactics, say, at steady state?
Yeah, I mean, I'm not gonna sit here and try to pretend and speculate on market segmentation. I mean, again, as a clinician, I sort of, as I've mentioned, we go over all the pros and cons, risks and benefits of all the agents and discuss with patients. And as you noted, route of administration is something that's important to many patients, and so some feel strongly about-
... an injected drug or an oral drug. The dosing frequency is important. Obviously, side effects or tolerability are important. I do think efficacy is, of course, right at the top of what people care about. So I think there are obviously some differences between the various options we have currently. So I guess I'm purposely dodging your question because I don't know how it will all shake out. I think that's something that's a little bit unpredictable, but as I mentioned earlier, I think options are good, and frankly, I think all of the existing treatments and some of those in the pipeline do show, you know, benefits for patients.
It is such a variable condition that it's good to have multiple options, and we use them all in our clinical practice.
Great. Thank you so much for taking our questions.
Thank you. And our next question today comes from Allison Bratzel with Piper Sandler. Please go ahead.
Hey, guys. Good morning. Congrats on the data, and thanks for taking my question. Really just a follow-up on some of the prior discussion, probably for Kyle, which is, you know, how do you anticipate the Switch data is gonna resonate with both patients and with physicians, and just what are your plans to incorporate it into the launch marketing strategy? You know, I think a lot of us have viewed this as a historically, like, sticky market. Is it your sense that the switching data can help overcome that stickiness? And then just secondarily, could you talk to how you think the Switch data kind of strengthens your hand when you talk to when you have those initial conversations with payers? Thanks.
Yeah, thanks, Allison. I appreciate the question. So, I think what our market research is telling us in the U.S. is that this definitely is a SWITCH patient population. There's still a high unmet need out there. The treatments that patients are currently on, in some instances, are suboptimal, and patients are looking for a medication that has the totality of a profile like donidalorsen has, right? They want something that works very well. They want something that is tolerable and something that is convenient to take. And the Switch data helps then inform how do you move from the existing therapies over to donidalorsen and do that in a safe and effective way. For patients, I think that's going to help because it's gonna create a level of understanding to be able to make the transition.
For physicians, I think it will help, because they're gonna be able to understand the current treatment that patients are on and, and have some guidance and some tools to use to say, "This is how I move over to donidalorsen and do it effectively," and it's been shown, exactly how to do that. I do think that it will, probably help as we speak with physicians, upfront, to be able to talk first about the profile of donidalorsen and the, the positive aspects of that, the clinical data that we've been reviewing, and then to show them how to do this with the SWITCH study, I think is, is really gonna add, added, confidence and, and added, I think, you know, emphasis in terms of being able to do this in the right way.
On the payer side, payers today are having to pay for multiple therapies 'cause there's overlap, because there's not a lot of knowledge out there and awareness in terms of how to switch, how long patients need to stay on one and transition to another. And so payers are telling us that, in this therapeutic area, they're having to pay for multiple drugs for a duration that they're really not understanding of. And so this data will help inform payers as well to say, "This is exactly how we move from one agent over to donidalorsen," and we expect that payers, when they're running their budget impact models and thinking about the cost and implications within their plans, will be able to take that into account. And I think that will definitely help us in our, in our discussions with payers in securing reimbursement for these patients.
Thank you. And our next question today comes from Yaron Werber with TD Cowen. Please go ahead.
Great. Thanks for taking my question and also congrats on the data. So I have two questions, one for the physician, please, and one for the company. I guess to the physician, as the drug gets approved, you know, in 12 months or so from now, you know, with the filing, do you give us a sense, kind of how do you think you're gonna use it? Do you call patients to switch them? Do you give them the offer, the option to switch? Do you use it in new patients immediately? And then to the company, the Q4-week data, as everybody sort of noted, looks better in the first 25 weeks, but as you stay on Q8 for longer, those two begin to look sort of similar.
Is that something that's gonna be in the label, so both options are given? Again, maybe even back to the physicians: Do you treat everybody Q8 weeks, or do you treat Q4-weeks and then switch to Q8 weeks? Sorry for all these questions. Thank you.
So I can start. You know, when new therapies come along, our practice is not to proactively contact patients, although this is a very well-educated and aware patient population, so they often contact us when there's something new that comes along. They're very in tune with developments. We do, though, however, as we see people back in our clinical practice, on average, we see these patients probably twice a year. If they're not doing well, we see them more often. Occasionally, we'll just see patients once a year if they're really doing well. But during their follow-up, one of our steps is to review what's new in the HAE space, and so that includes any new therapies that have been FDA approved.
And so that's a scenario where we discuss with them, you know, the new treatment option, the risk benefits and all the data that we've covered, and do that very briefly. And that gives us an opportunity, and the patient an opportunity to discuss whether they're interested in making a change in their management. So it's sort of on a rolling basis in the year that follows these new medication approvals. And so that allows us, like I said, to incorporate change for patients who may wanna switch therapy. And of course, with new patients, we go over, you know, all of the options that are available at the time, including sometimes investigational drugs, if patients are interested in clinical trials.
So, I would see this being, you know, discussed both with obviously existing treatment-treated patients, but certainly with newly diagnosed patients also.
Yaron, I'll, I'll take a stab at your second question, which is also a very good question. So first let me start by saying that, we plan to publish, the long-term extension data. You're absolutely right, that with the continued treatment, the every 8-week dosing, the, really, really competitive efficacy that we see with so every, 4-week dosing starts to look almost exactly like, like the every 8-week dosing. So very similar reductions in HAE impact to long-term treatment. We plan to publish this data, and we, and we'll continue to publish it. This, this study will continue for several years, is the plan, as will the switch study. It's ongoing. And that'll be very important for, physicians to see, how well the, the drug performs every eight weeks, long term.
Regarding the label, we believe that, we're gonna have all this data, it was certainly part of the submission package, and we expect, a good part of it to be in the label. That includes phase II data and the phase II open label data, the phase III and phase III open label, extension data, actually our Switch data as well. We think the Switch data will be, viewed by the FDA as very important data for physicians to be able to have on the label to see how to switch and what the results are of switching, how well patients are protected, and what the outcome of that is. And importantly, as I mentioned, the open label extension will also include data, long term on efficacy.
So, I cannot speak for the FDA, what will of course be in the label, but we're gonna push for all this to be in the label, and we're reasonably confident that a good part of it will be included.
Thank you. Our next question today comes from Yale Jen with Laidlaw & Company. Please go ahead.
Good morning, and thanks for taking questions, and congrats on the data. I just have two, one for Dr. and one for the company. For the doctor, that, the secondary endpoint, the week 5 to 25, I'm just curious, what's the value or difference between that from one, the primary data from one, week 1- 25?
Yeah. I think this is mostly recognizing the mechanism of action of the medication, meaning that, as you know, block the production of prekallikrein, you still have to use up the existing prekallikrein, which can take a couple of weeks, a few weeks. And so the, you know, the MOA, at least from a mechanistic standpoint, you would expect to be fully optimized or the pharmacodynamic effect to be greatest starting at about that month, the five weeks. So I think it's a little hard to know because we don't have measurements earlier than that.
It's possible that the drug could work faster, but I think that's the rationale for looking from 5- 25 instead of 1 - 25, is the recognition that it could take, from a mechanistic standpoint, it could take a couple of weeks for the effects to fully be realized in terms of knocking down those prekallikrein levels.
Okay, great. That's very helpful. And maybe the question for the company is that for the Tak, Takhzyro, my understanding is the patent will be expired this year or which maybe already expired. If that's correct, what do you think the impact also might be in the market size? And thanks.
I'm sorry, I'm not familiar with the loss of exclusivity on Takhzyro. I don't think any of my team is either, so we just can't comment on that, but maybe we can follow up with that. I'd just like to add to Dr. Riedl's statement, which I fully agree with, is that, you know, donidalorsen, donidalorsen is a first-in-class medicine targeting RNA for the first time, that we expect to reach the market next year. The onset of action is actually pretty quick. When you look at the reductions in HAE attacks, it actually you're seeing attacks reductions after the first dose, the single, the first single dose. The first time point in those graphs is at five weeks, so we don't really have reduction data earlier than that.
And then again, to emphasize, so that at five weeks after one single dose. I'd also draw your attention to the open label extension data, where placebo patients are converting over from placebo to donidalorsen treatment. And you can see how quickly that the patients are responding or responding really within a week or two to a single dose. So the onset of action for donidalorsen is actually quite, quite fast. And also the durability. So we'll be impressed. As far as weeks, getting back to weeks 1-25 versus weeks 5-25, we expect both of those data sets to also be in the label, assuming approval, because weeks 5-25 was a key secondary endpoint in the study.
Okay, great. Thanks a lot again, again, congrats.
Thanks, Jen.
Our next question today comes from Kostas Biliouris with BMO. Please go ahead.
Hi, everyone. Thanks for taking my question and congrats on the data. A quick question from us on the SWITCH study. You mentioned that 88% remained in the study. So I was wondering if you can provide a little color around this 12% that did not remain, was not remained in the study. Was the reason purely the attack rate that went up or any other feelings that these patients had that potentially made them switch back? And any characteristics of these patients that made the drug not to work very well in these patients potentially? Thank you.
Thanks, Kostas. Eugene, do you have any information regarding the, you know, very small percentage of patients that preferred their original prophylactic treatment, as Kostas said, I think it was around 10%, or less. Any reasons why? Any profile there, any phenotype?
Yeah, as I recall it, it's a number of different reasons. So it's a combination of things, and lack of efficacy is only one of those things. Really, you know, we have things like voluntary withdrawal and loss to follow-up. So again, as these open long-term extensions typically occur over the years, some patients just do not have the ability to follow up, and sometimes they discontinue. But certainly, I think in this case, we had only four of the eight who at least listed lack of efficacy as their primary reason for discontinuing from the study.
Yeah, Kostas, as has been raised by several analysts already on today's call, some view this market as a, quote, "sticky market," in which patients tend to stick with treatments that they have and more difficult to get them off. We don't necessarily agree with that position. We actually see patients switching because there is an unmet need, or they view it as they want better treatment options. So and it's one of the reasons why our SWITCH study went well, as quickly as it did. And it's also supported by the fact that, you know, almost 90% of patients prefer donidalorsen. So that percentage of patients is very small, that chose not to—that chose donidalorsen as not being their preferred choice.
Agreed. Very helpful. Thank you.
Thank you. Our next question today comes from Mike Ulz with Morgan Stanley. Please go ahead.
Hey, guys. Thanks for taking the question, and congrats on the data as well. Maybe just one on the SWITCH study. You know, looks like there was a slightly lower preference for donidalorsen when patients switched from lanadelumab. It was around 72%, you know, compared to the other two agents, which were north of 90, 90%. So just curious, you know, any factors driving that, that you could maybe shed a little light on? Thanks.
Eugene, would you take that, please?
Yeah, well, the data are what they are, and what we can say is, again, that I think Dr. Riedl already clarified that there were generally more than one reason for preference of a particular therapy. So it could have been a number of things. And of course, what we have seen were kind of the themes of preferring donidalorsen on the basis of efficacy, better efficacy relative to their old treatment, better convenience or better tolerability. Those are kind of the three buckets that dominated as rationale for preference. But some... And sometimes there was more than one, of course.
So, you know, 72% in a cohort that was exposed to kind of, and generally well controlled, is still a fairly large proportion of patients who really preferred donidalorsen to their previous treatment with lanadelumab.
Got it. Thank you.
Thanks. I think we have time for one more call.
Absolutely. Yes, sir. Our final question today comes from David Lebowitz with Citi. Please go ahead.
Thank you very much for taking my question. Earlier in the call, you talked about how all the data across the phase II, OLE, the SWITCH study, and of course, the pivotal will be submitted. Which of these components do you think stand out? Obviously, the phase II and III, certainly, but which other components do you think actually stand a reasonable chance of appearing in the label? And which would you think would be a tougher debate with the agency?
Thanks, David. As I mentioned earlier, we believe all of the data that I've summarized, phase II, phase III, their respective open-label extensions, as well as SWITCH data, will be. We certainly push for that to be in the label. And we expect that the data for all of those programs to be in the study. Certainly, if you wanted to draw one study, to you know, settle on one study, that would be the hardest to get all of the data in, would be the SWITCH study. This is not a randomized study. It's an open-label study. However, as I highlighted earlier, what matters to the FDA is what's most important for physicians, what's most important for treaters or and for our patients.
We believe that the data from the SWITCH study is, it would be incredibly valuable, not just for the FDA, to physicians, so that they understand how to safely switch patients from existing prophylactic treatments, to donidalorsen and what the, what the outcome of that will be, and what the data is that supports that. So we think because of the fact that this data will be, very highly, of high importance by the FDA, even though the, the study higher bar in the randomized trials, we believe that the SWITCH data will, will be, get into the label.
Thank you for taking my questions.
Thanks, David, and I'd like to thank everybody, once again for joining us on our call today. I'd also like to thank Dr. Riedl for joining our panel and providing his key insights into the significance of the phase III program for donidalorsen for patients with HAE. And with that, I want to thank everybody for joining us again, and have a great day. We'll talk soon.
Thank you, sir. This concludes today's conference. We thank you all for attending today's presentation. You may now disconnect your lines. Have a wonderful day.