Good day and thank you for standing by. Welcome to the KalVista Pharmaceuticals FDA approval call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Ryan Baker, Head of Investor Relations. Please go ahead.
Thank you for joining us to discuss the U.S. FDA approval of sebetralstat, now known by the brand name Ekterly, the first and only oral on-demand treatment for hereditary angioedema. On the call with me today from KalVista are Ben Palleiko, Chief Executive Officer, Dr. Paul Audhya, Chief Medical Officer, and Nicole Sweeny, Chief Commercial Officer. Brian Piekos, Chief Financial Officer, will join us for the Q&A session. Ben will begin with an introduction, followed by Paul, who will provide an overview of the current HAE treatment landscape and highlights from the Ekterly U.S. package insert. Nicole will then review the company's commercial strategy and launch plans. We will wrap up the call with a Q&A session. Please note that we will review a slide presentation during our webcast today, which will be posted to the KalVista website after the call.
Before we discuss today's news, I remind everyone that we will be making certain forward-looking statements that are based on our current expectations and beliefs. We encourage you to review slide two of the accompanying presentation in our SEC filings, which include detailed discussions of the risks and uncertainties that could cause actual results to differ materially from today's forward-looking statements. With that, I will now turn the call over to Ben.
Thank you, Ryan. Today is a monumental day for the HAE community and KalVista. We are pleased that the FDA has approved Ekterly as the first and only oral on-demand treatment for hereditary angioedema attacks in people ages 12 and older. This approval represents a major milestone, not only as the first commercial product for KalVista, but more importantly, as the first new on-demand HAE therapy in over a decade. Ekterly delivers a long-awaited treatment that is safe, effective, and easy to take anytime and anywhere. I first want to take a moment to thank the patients who participated in our clinical trials, the investigators around the world who conducted those trials, the HAEA and HAEI for their outstanding patient advocacy efforts, and my fellow KalVista colleagues for making today possible.
The brand name Ekterly is a call to action for people living with HAE to act early when treating their attacks. From its conception, Ekterly was designed to enable people with HAE to comply with global guidelines, which strongly recommend treating attacks as early as possible, prior to the progression of swelling, thereby avoiding disabling symptoms caused by HAE attacks. Ekterly represents our deep commitment to the HAE community. It reflects years of collaboration with people living with HAE to understand their experiences and significant need for an oral treatment that can easily be taken at the onset of an attack, regardless of severity or wherever the patient is at the time an attack starts.
Paul will discuss the label details in a few minutes, but as a headline, I will note that Ekterly is approved for all HAE attacks with no restrictions, either for severity or regarding the anatomic site of an attack, including the larynx, where speed and ease of administration can make a dramatic difference in treating an attack promptly. Given its unique efficacy and pristine safety profile, we believe Ekterly is poised to become the foundational therapy for HAE management worldwide. With that, I will now turn it over to Paul to discuss the current treatment landscape and then review key elements of the Ekterly label.
Thank you, Ben. I'm Dr. Paul Audhya, Chief Medical Officer at KalVista . I'm excited to share some context for the Ekterly label and take you through some of the key details. As a reminder, hereditary angioedema, or HAE, is a rare genetic condition that affects approximately 1 in 35,000- 50,000 people, roughly 8,000 people in the U.S. As you can see in the pictures, HAE causes unpredictable swelling attacks in various parts of the body, including the face and extremities. Swelling in the airway can be life-threatening if not treated. Attacks most often start as mild, but severity can increase quickly. They can also migrate to other anatomic locations, including the larynx. Depending on the tissues affected, attack symptoms can last one or two days, but may persist for up to five days if left untreated.
As noted in the current treatment guidelines, the main goals of treatment in HAE are to achieve total control of the disease and to normalize the lives of patients. To realize those goals, there are two main strategies. Number one, ensure that all HAE patients have ready access to effective on-demand treatment, which ideally offers rapid symptom relief, easy self-administration, allowing for early treatment, and a good safety profile. Number two, consider the addition of long-term prophylaxis, or LTP, in appropriate patients, which means evaluating the frequency and severity of attacks, the impact of those attacks on the patient's quality of life, and whether adequate control has been achieved with an on-demand treatment. Let's spend some more time on that last slide. Treatment guidelines recommend that patients consider the treatment of all attacks, regardless of severity, as early as possible after onset to minimize symptoms and reduce attack duration.
In order to achieve this, patients should be well-trained and have ready access to adequate on-demand medication to treat at least two attacks. This translates to carrying the medication at all times when leaving home and when they reach at home, even at nighttime. However, all approved on-demand treatments require administration by subcutaneous injection or intravenous infusion, which present clear barriers for people living with HAE. Therefore, while injectable treatments may be efficacious, they may not be effective. Common barriers to early treatment include anxiety associated with pain and injection site reactions, difficulty injecting and especially infusing treatment, the lack of a private and hygienic location to administer medication outside the home, and challenges with portability. As a result, patients frequently avoid treatment, and for some, the therapy may be perceived as more painful or challenging than suffering through an attack.
Indeed, observational studies reveal that up to half of attacks go untreated. For attacks that are treated, patients often wait until the swelling becomes severe and thus delay therapy for hours. This is most dramatic in adolescents, a population where Ekterly is not approved. Perhaps it's not surprising that, given the logistical burden, less than 40% of patients carry their on-demand treatment all the time when traveling outside their homes. Underutilization of injectable on-demand treatments in the form of delays and denial leads to inadequate control of HAE attacks. As a result, physicians and patients have turned to LTP as an easier alternative. Despite prior advancements in HAE, the promise of total control of disease and normalization of patient lives hasn't yet been achieved. With the approval of Ekterly, we believe the treatment paradigm is ready to change.
For the first time, people living with HAE can take an oral on-demand treatment at the first sign of an attack and achieve symptom relief in the same time frame as injectable therapies. Ekterly has the potential to transform the management of HAE, truly empowering patients to comply with the guidelines to help control and normalize their disease. It is reasonable to say that injections will never be normal. By overcoming the barriers imposed by injectables, Ekterly is poised to become the new foundation of HAE treatment. With that background, I'm extremely pleased to share the prescribing highlights from the U.S. package insert. Ekterly, an oral plasma kallikrein inhibitor, is indicated for the treatment of acute attacks of hereditary angioedema in adults and pediatric patients age 12 and older. Ekterly has been approved with a recommended dose of 600 mg taken orally at the earliest recognition of an HAE attack.
A second dose of 600 mg can be taken three hours after the first dose if needed. The maximum recommended dose is 1,200 mg in any 24-hour period. Further along, you'll note that there are no contraindications and actually no warnings or precautions at all. The adverse reactions at the top on the right only include headaches, which were noted to be uncommon but marginally higher than placebo. Regarding the potential for drug interactions related to CYP3A4 or in the setting of hepatic impairment, those reductions are recommended for strong and moderate CYP3A4 inhibitors and in those with moderate hepatic impairment. There are also recommendations to avoid the use of Ekterly among those taking strong CYP3A4 inhibitors and moderate or strong CYP3A4 inducers, as well as those with severe hepatic impairment. Overall, these represent an extremely uncommon group of patients.
Moving on, I'd like to walk you through some key takeaways from different sections in the label. First, in section one, on indications and usage, both adolescents and adults were included. Adolescents may be the population with the greatest unmet need, as they have the longest treatment delays and difficulty managing their HAE attacks today. There's also no restriction on the type of HAE, so the opportunity to bring Ekterly to all HAE patients in the U.S. with persisting unmet needs is possible. Additionally, you'll note that there are no restrictions with regard to attack severity or location, including laryngeal attacks, and no restriction on LTP breakthrough attacks, regardless of LTP mechanism of action. This represents the largest number of treated attacks in the U.S., as the majority of HAE patients are receiving LTP, and many continue to have attacks in all locations and severities.
In section two, dosing and administration, Ekterly's label is the only one to include at the earliest recognition of an acute HAE attack, which is the very heart of treatment guidelines and reflects the most significant advance that comes with Ekterly. We're also pleased that 600 mg is the recommended dose, as we believe it provides a deeper, longer inhibition of plasma kallikrein without any impact on safety. We also believe that 600 mg represents an optimal dose for HAE attacks based on overall outcomes in the phase III KONFIDENT trial and the extensive experience to date in the KONFIDENT open-label extension. This flexibility to use a second dose after three hours also exemplifies Ekterly's excellent safety profile. All of this is consistent with sections four and five, where there are no contraindications, warnings, or precautions. Moving on to section six, the table says it all.
Adverse reactions only comprise headache, which occurred in about 3% of patients receiving Ekterly 600 mg and 1% for placebo. Again, this reflects Ekterly's pristine safety profile, which underlines the opportunity to have 600 mg as the recommended dose. Section 12.3, pharmacokinetics, you'll note two important recommendations. First, with 600 mg, there is greater than 90% inhibition of plasma kallikrein maintained for six hours, which supports optimal management of HAE attacks and increases the potential for low redose rates. The second is that there are no restrictions regarding food intake. In other words, Ekterly can be taken with or without food. Lastly, clinical studies, Ekterly's label is the only one to include statistically significant faster times to beginning of symptom relief, reduction in attack severity, and attack resolution.
Starting in the lower right-hand corner, the pre-specified analysis of the primary endpoint for the phase III KONFIDENT trial was published in the New England Journal of Medicine in May of 2024. There, the median time to beginning of symptom relief for Ekterly 600 mg was 1.79 hours and 6.72 hours for placebo. However, what you'll note in the clinical study section is that the medians are based on utilization of a more conservative censoring approach to analyzing the primary endpoint. Basically, for about 5% of total attacks, patients didn't record responses to treatment in their eDiary. In the pre-specified analysis, for those attacks, we censored them to zero, essentially counting them as neutral in the analysis, as we don't know whether they improved or didn't improve over 12 hours.
In the alternative analysis, these attacks were considered as not having reached the endpoint within 12 hours, i.e., right censored at 12 hours, which assumes the worst possible outcome. To clarify this change in methodology, there is a footnote for each of the endpoints under each efficacy figure in the clinical study section. The result of this change was that the separation between Ekterly 600 mg and placebo starts earlier and is wider, but it also shifted out the median slightly for Ekterly to 2.0 hours, or about 12 minutes longer, but much further out for placebo, which no longer reached the median within 12 hours. I'd like to finish this overview with some of the data we've reported this year from KONFIDENT, our ongoing two-year open-label extension.
As a reminder, this trial has many real-world design elements to gain insights on Ekterly's potential to improve compliance with on-demand treatment guidelines. First, amongst 1,706 attacks reported through September 14th, 2024, we see a median time to treatment of 10 minutes. We also observe a median time to end of attack progression of 19.8 minutes. This highlights a rapid response to treatment almost immediately after absorption of Ekterly. Finally, we've seen a consistent rapid response among attacks that have been highlighted as the most concerning to physicians, including laryngeal, abdominal, and LTP breakthrough attacks, all of which have demonstrated median time to beginning symptom relief of 1.3 hours. On the right, as of June 2025, we've captured approximately 700 additional attacks since September 2024, which now includes 2,323 total attacks, 48 laryngeal attacks, 974 abdominal attacks, and 463 LTP breakthrough attacks.
Before KONFIDENT completes next year, it will be among the largest treatment experiences ever collected in a clinical trial for on-demand product. We look forward to sharing new results from KONFIDENT later this year, including data on the very high level of treatment satisfaction among participants treating attacks with Ekterly in the trial. I'll now turn the call over to Nicole Sweeney, who will share how we plan to commercialize Ekterly. Nicole?
Thank you, Paul. I'm Nicole Sweeny, Chief Commercial Officer of KalVista . I'm excited to talk about how we are working to put Ekterly into patients' hands as soon as possible. I want to reinforce a point that Ben shared earlier. Ekterly is based on a call to action for people living with HAE to act early when it comes to treating their attacks. For the first time ever with Ekterly, they are able to do so. Ekterly is the first and only oral on-demand HAE treatment. This allows patients to discreetly carry treatment with them at all times so they are prepared for their next attack. Each dose offers injection-like efficacy. It's proven to halt progression quickly and safely without any needles or pain. Ekterly has been demonstrated to be safe and effective in treating all attacks, all attack locations, and all attack severity.
Additionally, as Paul mentioned, Ekterly has been FDA approved for use in adults and children 12 years of age and older. This is particularly meaningful for the adolescent population as Firazyr icatibant are not approved for use. Our commercial team will be selling Ekterly in physician offices this morning. Our team is poised to drive swift demand. Our payer team has been educating national and regional payers for the past year. Our field sales team is competitively sized, which provides complete national coverage of HAE prescribers. Our commercial team has decades of combined experience in HAE, rare disease, and high-performing product launches. Leadership and field teams include professionals who have successfully launched both prophylactic and on-demand HAE therapies. As most sales reps have worked in the HAE space, they have strong relationships with target prescribers and knowledge of how these accounts adopt a new HAE therapy.
Our field team is focused on driving early Ekterly adoption with the top 1,000 healthcare professionals that account for 90% of HAE claims today, as this is where the highest patient concentration and unmet need exists. They will reach the remaining 10% of prescribers as the summer progresses. Our field team has been active in these target accounts since February, providing disease state education, and will now pivot to product education. The team has appointments in place for the month following approval, with virtual speaker education lunches to reach the entire care team within key accounts. Shifting gears to the patient community, our goal is to introduce Ekterly and ensure people living with HAE can have informed discussions with their physicians about making a treatment change.
Within a few weeks of launch, we will host patient education programs where patients who utilized Ekterly in the phase III clinical trial will share personal experience with the HAE community around the country. In addition, we will participate in the HAEA patient summit meeting, which kicks off July 10th. This meeting happens every two years and brings together people living with HAE and their families to connect and learn more about developments in HAE. For KalVista, this creates an opportunity to introduce Ekterly to over 1,200 members of the community. It's a tremendous event, and the HAEA is a deeply valued partner to KalVista. On the access side, both our KalVista patient hub, KalVista Cares, and QuickStart programs are live. QuickStart provides patients immediate access to Ekterly at no charge during the time period their claim for paid access is in process.
Each Ekterly pack includes two doses or four tablets. Tablets are provided within wallet-sized blister cards, which provide discreet access to therapy. We anticipate product availability mid-July. Ekterly is the first new on-demand treatment approved in over a decade and the first oral option ever. We continue to hear from healthcare professionals and patients that Ekterly fills a clear unmet need in HAE treatment. We price Ekterly competitive to existing branded therapies in the HAE market. We believe this pricing reflects the innovation we're bringing to the community and will support broad utilization. Lastly, we've taken a comprehensive approach to ensure access support, which includes KalVista Cares, our patient hub. From reimbursement support to QuickStart access, our infrastructure is built to minimize delays and help people start therapy quickly. As a company, we understand the importance of delivering accurate and timely visibility into launch progress.
Based on historical rare disease launches, we know that third-party data sources can often lag or present an incomplete picture, especially in the early weeks of commercialization. We recognize that we will need to share regular updates externally. In the early days of launch, KPIs will focus on awareness and engagement efforts in the field, as well as QuickStart demands. As launch progresses, we will share greater insights that reflect broad adoption by key stakeholders. We're incredibly proud to introduce Ekterly, the first oral on-demand HAE treatment, and believe there's a clear path for Ekterly to become the foundational treatment in HAE. Our launch strategy is focused and intentional. Today, we will start by driving early demand with patients who have communicated the highest dissatisfaction with current therapies, particularly patients on Firazyr and icatibant. From there, we'll accelerate adoption by converting patients on all on-demand therapies.
As utilization expands and patients experience the benefits of Ekterly, we expect treatment rates to rise and the on-demand market to grow. The opportunity is significant, and we are ready. The infrastructure is in place. Our field team is deployed. The KalVista Cares patient support hub is live. This is an immediate launch backed by years of preparation and deep expertise in HAE product launches. I'll close by extending a heartfelt thank you to members of the HAE community who supported our trials and helped us reach this moment. We're excited to bring this life-changing treatment forward to the HAE community. I'll now pass it back to Ben.
Thanks, Nicole. Picking up from where Nicole left off on this slide, we anticipate that the on-demand segment of the HAE market will grow by 70% with $1.2 billion by 2030, a significant portion of which will be fueled by the introduction of Ekterly. For the first time, patients have access to an oral on-demand treatment that provides the opportunity to change how and when attacks are treated. As a result, in addition to the general transition to Ekterly that we expect, we also expect to see an increase in the overall attack treatment rate, as people with HAE are more willing and able to treat attacks that currently may go untreated for many reasons. With FDA approval of Ekterly now secured in the U.S., we're also preparing for global expansion, beginning with the potential EMA decision and a targeted launch in Germany later this year.
In the first half of 2026, we expect to launch in Japan in collaboration with our partner, Kaken Pharmaceutical , as well as in the U.K., pending local approvals. Additional market launches are planned in 2026 and beyond, including Canada, where we recently entered into a licensing agreement to support approval and commercialization. As we finish this part of the call, a quick anecdote to highlight how we think Ekterly can change HAE management. At a recent conference, I met with a physician who relayed to me a real-world story about one of his patients who's been using Ekterly. She was driving her car to work one day recently when she felt an oncoming abdominal attack. Historically, she's used icatibant, which would have made treatment of the impending attack impossible without major changes to her day. Abdominal attacks are among the most painful to endure.
However, in this case, at the next stoplight, she pulled out her Ekterly wallet, took her dose, and continued to work. She reported to the physician at her next visit that her attack didn't progress further, and within about an hour, she felt fine. This is exactly how people with HAE should be able to manage their disease and reflect the results we have seen to date in the data set that is closing in on 2,500 treated attacks. This is also why we believe Ekterly is poised to fundamentally transform the HAE treatment landscape. It has the potential to replace injectable, painful, and cumbersome on-demand options with an oral therapy that directly addresses treatment burden while providing the necessary efficacy and safety that people living with HAE expect. We believe Ekterly could become the treatment of choice among adolescents, adults, and, if approved in the future, pediatrics.
In closing, we're incredibly proud to bring Ekterly to people living with HAE as an innovative oral therapy that redefines what's possible in HAE management, and we are fully committed to delivering its impact on day one and every day after. Our infrastructure, team, and strategy are fully in place to deliver a successful launch and sustained performance, and we look forward to providing further updates in the near future. With that, we'll now open the call for your questions.
As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Paul Matteis with Stifel.
Great. Thanks so much, and congrats on the approval. I was wondering if you could share more color on the metrics you plan on sharing early in the launch and how those metrics might evolve over time as you get more information. I have one follow-up. Thanks.
Hey, Paul. Good morning. Thank you for the question. I'll actually ask Nicole to give the details there.
Sure. Thanks, Paul, and good morning. As shared earlier on our call, looking at the early days and weeks of launch, we plan to share forward information just about engagement with our key accounts in terms of the frequency and engagement with our tier one, two, and three accounts, as well as engagement with the patient community. In addition to that, we will provide updates on demand in a general sense in terms of QuickStart requests and start forms that are being processed. Certainly, as the launch takes hold, what will be of keen interest to us, as well as I'm sure you and others, will be repeat use. In the weeks and months following that, we will share updates as we see repeat prescriptions coming through those key accounts as well as refills on a per-patient basis.
In addition to that, during the course of the upcoming months, we will also provide a view into payer engagement and a view into how the formulary process is unfolding.
Okay. Great. Thanks. Just two quick things to clarify there, Nicole. One, in the open-label extension, what did you see in terms of the frequency of use? Do you think that's a good benchmark for, you know, real-world use? Two, on your point on getting on formulary, I guess, as I understand it, right, everything in this category is reimbursed via special medical exemptions. How much does actual formulary access really matter here, and how much is payer access even really going to change over time?
Sure. Why don't I address your second question first, and then I'll turn it over to Paul. As with other HAE products, we do anticipate in the early months of launch that medical exception will be the primary means for an individual to gain paid access to Ekterly. Certainly, the payers have indicated that they typically take about six months to see how demand comes in for a new product, and then they'll set their formularies at the close of that six-month time period. As with other HAE products, we anticipate heavy medical exception for the first six months of post-approval.
On the first question earlier around frequency of use in our open-label extension, we are seeing upwards of 80%- 85% of attacks being treated. It's exactly what we expected, that the rate would be much higher than we see in observational studies with the injectable drugs, which are basically a half, really to a maximum of about two-thirds. This is really much higher.
Thank you.
Our next question comes from Maury Raycroft with Jefferies.
Hi. Good morning. Congrats on the approval milestone, and thanks for taking my questions. Just based on the patient interest you're seeing from your awareness website and doctor interest, how are you setting expectations for the early launch? As a follow-up to Paul's question, can you talk more about how you'll customize drug supply for patients with different monthly attack rates and what you think the typical prescription and supply will look like for patients?
Maury, on the second part, at least, going to that part first, we have KalVista Cares, as we talked about, set up as an organization that will be in close contact with patients as we go forward. The idea here is that patients will get their initial box of Ekterly, but we'll be checking in with them routinely to make sure that their supply isn't running low and making sure they always have sufficient amount on hand to be comfortable treating attacks. We do know that one of the reasons people don't treat attacks is the fact that they worry about not having it available when they really need it. The idea is to make sure that they're never in that position. On the first part of the question, you know, Nicole, you can answer that.
In terms of the prescriptions and how we anticipate a physician writing a prescription for Ekterly, we anticipate that the initial fill will be for one box of Ekterly, and then they will write, similar as they do to other on-demand treatments, PRN, refill as needed. That is an approach physicians take today, recognizing that the burden of disease and the number of attacks really varies from one of their patients to the next. Therefore, we anticipate, again, they would take that similar PRN approach for Ekterly.
Got it. Okay. Thanks for taking my questions.
Our next question comes from Deebanjana Chatterjee with Jones.
Hi. Thanks for taking my question and congrats on the approval. Could you expand a little bit more on the drug interactions, labels, and if, you know, how it might have any influence on the uptake?
In terms of drug-drug interactions, we did some studies. We see that with moderate CYP3A4 inhibitors or those that have stronger inhibition or induction, it can increase or decrease the concentration. It's overall a relatively small population that have these other drugs on board. We don't actually think that it's going to have very much impact at all. In terms of the exposure or experience that we've had with this, in doing our open-label extension or clinical trials, there are very, very few patients who were not eligible due to use of these other therapies. We don't think it's going to really have any material impact. Again, just as a reminder, HAE patients are patients who don't have a significant number of other comorbidities, and because of that, they're not really using these drugs in a meaningful way. We don't think it'll have any impairment on uptake.
Thanks for that. I have a quick follow-up. How should we think about the growth to net as the launch progresses?
We're going to bring Brian Piekos in here to pick up those questions.
Hi. The gross to net will be on a long-term basis, typical for what you see in rare disease in the upper teens to low 20%. As we're getting through the launch and there are some fixed fees, the gross to net may be slightly higher. Again, it'll quickly normalize to that rate we just talked about.
Great, thank you so much.
Our next question comes from Joe Schwartz with Leerink Partners.
Thanks very much, and congrats on the great achievement. Do you see any different phases to the Ekterly launch? For example, are there early, mid, and later adopters? How would you characterize different subgroups as you look at the HAE patient population? I have a follow-up.
Yeah. Joe, I'll start, and I think Nicole can pipe in here. When we talk to physicians, we do hear that effectively they believe Ekterly is appropriate for everybody. We don't actually see them making any distinctions between different populations that might have a greater or lesser need for it. It seems to be very confident that there's a uniform desire among patient populations to have access to this. I think the data set we've generated, which shows efficacy in all these important subgroups, right? I mean, abdominal attacks and people on LTP and certainly laryngeal attacks, that has really become the basis of this physician enthusiasm, which is there's effectively no subgroup where we've shown that this doesn't have a substantial improvement in terms of their time to symptom relief and sort of control of their attacks.
As a general comment, which may be a little bit simple, the physician community we think is going to want to talk to effectively everybody about this. In terms of from the patient side where the greatest pull will be, I think certainly, Nicole, you've got some thoughts on that, and we can talk a little bit more detail about who we think will be the first calls to the offices.
Yeah. Absolutely. You know, with research that we've conducted with patients that are utilizing various on-demand as well as prophylactic plus on-demand treatments, we see that the patients that have experience and are currently on icatibant and Firazyr express the greatest impact, excuse me, interest in adopting Ekterly quickly. That was about 80% of the Firazyr and icatibant patients, communicating a high interest in adopting Ekterly. Just one other thought going back to the physician side of things. As our sales team has been in the field profiling all of the physicians, all 2,000 physicians, the tier ones, twos, and threes, we see interest and high interest to utilize Ekterly throughout those tiers.
To answer your question, certainly anticipate the earliest adoption, those earliest prescriptions to come in from the tier one physicians as they manage those patients that have the highest unmet need, and really signal the highest urgency to try something new with Ekterly.
Thanks. That's a very helpful color. As a follow-up, I'm just wondering, especially a question we get from investors pretty frequently, what will a patient or their physician need to demonstrate in order for a patient who's on generic icatibant to be eligible for a Ekterly prescription?
Yeah. Today, that is, today there are patients that, to move off of icatibant, I think that's what you're referring to, to demonstrate that failure on icatibant is actually a fairly low bar in terms of what is utilized today. It can be feedback from the physician and the patient, recognizing that the patient doesn't tolerate that product. That could be injection site reactions as well as specific reactions that happen in the abdomen area, as that is where the product is administered. Oftentimes, individuals have abdominal attacks. We most commonly hear that it's just injection site reaction of any kind, which, as you know, being familiar with the Firazyr phase III studies, nearly all patients in the phase III studies experience those reactions. Again, fairly common and something that can be moved forward fairly quickly in terms of demonstrating a failure on icatibant.
Okay. Makes sense. Thanks. Congrats again.
Thanks, Joe.
Our next question comes from the line of Serge Belanger with Needham.
Hi. Good morning, and congrats on the approval. The first question regarding, for a potential second dose, I think in the KONFIDENT trial, about 40 patients redosed. I'm not sure what you've been seeing in the KONFIDENT open-label trial, but just curious what level of redosing you expect to see in the real world. Secondly, does Orladeyo represent kind of a potential proxy for what the Ekterly launch could look like, at least in the initial stage? Thank you.
I think the first part. With regard to the redose rate, you're correct in KONFIDENT, which was the double-blind study. Patients have the option to take an additional dose at three hours, and there were very few restrictions in that regard, and many patients went in and took advantage of the opportunity to take the initial dose. In the real-world study, KONFIDENT, what we see there is about a 22%, 23% redose rate, with the same dose that's approved in the label. That's what we do expect to see in the real world. We've seen over 2,300 attacks treated, and so the exposure and that we've learned is good. Again, just to remember, as a comparator with Firazyr, that tends to be between 25% and 40% depending on the observational data that you look at. This is certainly well in line, if not a little bit less.
I'll turn on the second part over to Ben .
It's important to remember with regard to the Ekterly launch that prophylaxis has got a fundamentally different sort of revenue profile because obviously when people start paying commercially, that's just a constant number. I think what we've consistently said to folks is, in terms of the uptake, like a sort of a unit type of curve, we do expect it to follow a kind of a traditional launch curve. You can even look back to the Firazyr curve to get a good idea. The Firazyr curve, frankly, looks a lot like the Ekterly curve from a units perspective. From a revenue perspective, it'll certainly be somewhat different.
It'll be a little bit of a longer initial point to get to the revenue side just because, again, people are refilling as needed, and because of the QuickStart program, effectively everybody will get their initial box without needing to pay that. Again, the curve overall we think looks about the same, but when we talk about that, we focus really more on the units curve as opposed to the revenue curve.
Thank you.
Our next question comes from the line of Stacy Ku with TD Cowen.
Thanks so much for taking our questions. Congratulations on the Ekterly approval. We know that it's just in time for the HAE community patient summit, which should be key. Our first question is on the first mover advantage that you all have. Can you discuss how you could really fully execute on that? It sounds like you're getting a running start with clinician outreach today. Just remind us what's the expected timing for your sales force to reach and educate the 1,000 tier one prescribers, which we believe you said in the past you've already kind of had a lot of interaction with. That's the first question. The second is on Ekterly and Firazyr efficacy. In general, our KOLs view the phase III and open-label extension data as showing similar efficacy.
Nicole, based on your commentary on prescriber and patient activation, can you go into more detail around the launch strategies that you think are key for helping clinicians and patients gain experience just to ensure that the community gets the same conviction as KOLs that Ekterly is performing similarly to Firazyr ? Thanks so much.
In terms of the first mover advantage, we've got a lot of things we've put into place here over the last several years, actually, and pretty intensively over the last six months. As you note, Stacy, we've had a field team out, doing physician education and activities, since late February. Of the 2,000 physicians who are in our database, they've contacted all except maybe a relatively small number of the tier three types. All the tier one, which is about 200 physicians, I'm quite sure we've seen multiple times at this point. The tier twos, which is the next 800, we've seen most of them multiple times. There's a very high level of awareness on the physician side here that we're comfortable is going to come into play here to our benefit. On the patient side, obviously, you really can't do any of those activities until approval.
Over the past year, we've developed a database of patients who chose to opt into communications from the company. As of approval, that is just shy of 3,000 patients, which again is certainly a third, maybe closer to half of the entire population in the U.S. A very sizable group of people have indicated desire to get more information. As of today, they will start to get that information. That's going to very quickly move out to them. That will only be enhanced by the patient summit that starts at the end of this week, which has between 1,200 and 1,500 attendees typically. That's another terrific group for us to get to. The activities have started today. The field team is actually already out and making calls as of this morning.
A lot of these communications have already been kicked into gear and will escalate here over the next few weeks. The desire, the goal is to very quickly get as broad a reach as we can here with both those populations, get everybody activated, and allow this to move at a fairly rapid foot. I think over to you for the second part.
Yeah. Stacy, just in terms of the ideal launch and how this all needs to come together, as we've talked about in the past, it's really making sure that we're supporting both the offices and the patients to have that dialogue as soon as possible regarding making a treatment change to Ekterly. From the office side of things, just to expand upon some of the work that's underway, as the team was in the field profiling accounts, they profiled all 2,000 accounts, so all of the prescribing HCPs. They were able to get a sense from the accounts whether or not, the degree, I should say, to which the accounts saw and recognized a higher unmet need for a new on-demand treatment. Those insights are what we've utilized to really prioritize the accounts, particularly for the first 90 days.
As you can imagine, we had lengthy business plan reviews to go through to see where the potential opportunity is for all of those accounts, specifically looking at the first three months of launch. In addition to that, as Ben was mentioning, we have planned supportive education programs, not only with the physicians but with all of the care team members in those accounts. We will be having speaker education programs with key opinion leaders to share their experience from the clinical trials with all of those accounts. On the patient side of things, we'll build upon the patient summit, which is coming up this Thursday, where we have a number of educational programs to reach patients throughout the country. This is important because we will have patients from our phase III trial share their trial experience with Ekterly with other members of the patient community.
This is something that has been absolutely critical to the success of other launches in HAE. The last point that I'll mention is, from patients, as we've gone and done a number of research, when it comes to adopting a new HAE therapy, some of the common barriers that we've heard relate to concerns about access or potentially the efficacy of the product. Again, this is any HAE therapy. Those are the barriers. That's really where the QuickStart program plays a key role because it allows not only the physician to prescribe and get that experience, but more importantly, the patient, that they can get that real-world experience with the drug to build the trust and really start to fully adopt that product while our team, the KalVista Cares team, works rapidly to ensure paid access. Those are probably some of the key elements.
As a last point, I'll just say that we didn't want to talk about this too much today because it's a future set of presentations for us. We've obviously started to do some surveys already in terms of patient satisfaction, treatment attacks with Ekterly. Suffice to say, they're extraordinarily high. There's a lot of patients, big enthusiasm for how well this works for them. That's the kind of data set that we'll start to flow out later on this year at different conferences and things to start to give more evidence about how well this actually works for folks compared to their current therapies, which, as we've said before, in most cases, is called the standard therapy.
Okay. Wonderful. Thanks so much for the detailed commentary.
Our next question comes from Tazeen Ahmad with Bank of America.
Hi. Good morning. Thanks for taking my questions. A couple from me. Can you clarify whether or not you're going to be doing sampling in the early part of the launch and how we would get color on how much abuse could be coming from sampling if you are doing that? Secondly, with regards to the label, it's allowing the second 600-mg dose to be used if there's an inadequate response or recurrence after three hours. Wanted to ask about how you expect that to work in a real-world setting and how that compared to what you saw in the KONFIDENT study.
Sure. Your question regarding sampling, at this time, we are not planning to introduce the sample program into the community. Our view is that the QuickStart program, which is important to note, allows that free product for that, allowing that immediate utilization of Ekterly, but that is done in parallel with the start form. From our view, we want to make sure that not only we're providing free access to therapy, but also in parallel moving forward to obtain that paid access for the individual. We do not plan on utilizing a sampling program at this time. I'll turn it over to Paul for the second part of your question.
Yes. In KONFIDENT, which is actually our open-label extension, kind of set up like a real-world study where patients make all the decisions as to how they're going to dose and whether they're going to use therapy, we've seen that patients will, in fact, choose to use that about 22%- 23% of the time with that 600-mg dose. That's what we expect to see in the real world. This is just going to be pretty typical for these medications. Most of the therapies that are here do allow for redosing. Obviously, the benefit for us is that it can happen in a shorter time frame than Firazyr, for example, which is six hours. Here, after about three hours, the patient will be educated that they can take additional doses if needed. We've had really no issues with understanding on that front.
Over 2,300 attacks have been treated in that open-label extension state. As I mentioned, in those 20% of the cases, there are really no issues with redosing. They also have portable packs that they could carry with them. In the open-label extension, which is quite similar to what we'll have with the launch, actually, what it will be with the launch will be far easier than what we had in the clinical study. Even there, we had no issues with the understanding as to when to take it and under what circumstances a patient might need it.
Our next question comes from Pete Stavropoulos with Cantor Fitzgerald .
Hi, Ben and team. Congratulations on the approval. Nice to see this get over the goal line. There are about 100, 130 patients in the KONFIDENT, the OLE, over 2,300 attacks treated. Curious to hear the feedback that you're getting from treating physicians and patients in terms of the comfort level around using Ekterly and any new trends. I know you mentioned about 23% redosing. Any new trends on taking a second dose to treat an attack as these patients get experience with the drug? Any sense on the impact on the quality of life for these patients? That's the first question. The second question I have is, as you touched on different patient populations and expectations for uptake, those on LTP and those on on-demand only, do you have a sense of the ease of getting a prior authorization for those different populations?
Will they be similar, or do you expect differences? Thanks for taking my questions.
Okay. On the first question with regard to taking a second dose, what we have seen over time is that actually, the proportion of patients who take or the proportion of packs which the second dose is used actually is trending downwards a little bit. That's the trend we've detected to date. We've done two interim analyses, one in January of 2024 and then again in September. We will be cutting that data again later on this year to be able to see if there are any additional changes. It has kind of stabilized around that 22% number, which again falls into line with what we may have expected. In terms of quality of life, we didn't have specific quality of life measures set up just because it's an intermittently dosed drug.
What we have observed in our preliminary assessment of satisfaction is that there are very, very high rates of satisfaction among the patients for each attack. So 24 hours, we ask the patient, "How satisfied are you with basically Ekterly for this attack?" and we see very, very high rates. We'll be putting out data later this year to highlight that. What we're seeing is that patients are treating large numbers of attacks. We have some patients that have treated over 60 or 70 attacks over the last couple of years and consistently have seen positive results and haven't really opted to change their therapy. Most of them are using it into and through the course of the full two years of the study. We'll start seeing all the patients coming off next year. A number of those have even transitioned to early access.
There's been a consistent interest in improving the dosing with Ekterly. All positive.
I think the slide that Paul presented, it really shows everything that's really important, which is all the data continues in the open-label to look, if anything, better than if it's in phase III. I mean, time to treatment is really short. High proportion of attacks treated. The time to initial symptom relief, you know, especially in these important subpopulations we've looked at recently is really impressive, down to about 1.3 hours. We think that's a terrific number. The open-label, again, being more real-world, has certainly evolved over the longer time into what we think is an even stronger proposition in terms of the value and the advantages it can offer to people with HAE. Do you want to go to the other question?
Sure. Absolutely. In terms of prior authorization, today, nearly all patients on a prophylactic treatment also have access to an on-demand treatment. Whether a patient is on prophylaxis or not, the requirements for a PA for the on-demand treatment are essentially the same. We don't anticipate that to be any different, relative to Ekterly.
It's important to note also that essentially everybody has a prescription for an on-demand medication whether or not they use prophylaxis. I mean, it's probably more than 90%.
Yes.
There is no difference in the need for a prescription or in just, you know, any way of how one gets it filled.
Now, I'm going to give you, when I say prior authorization, I don't mean for an on-demand treatment itself, but, you know, basically, let's say two branded drugs, LTP versus, you know, on-demand. Any perspective?
Yeah. No, I mean, people have that nowadays. There's quite a grouping, right? Berinert, Kalbitor, they're all approved. They're all branded, and there's no differential for them.
All right. Congratulations once again. Thanks for taking the question.
Thanks, Pete.
Our next question comes from Jon Wolleben with Citizens.
Hey, congrats, and thanks for taking the question. I know you guys gave us the metrics you'll be looking at early and mid-launch, and with expectation revenue may lag some of those early indicators. I was hoping you could give us some of your internal benchmarks on how things should be tracking so we can see if you guys are hitting your internal targets and how things are progressing relatively early on.
Yeah, Jon, as you know, it's extraordinarily common in these kind of situations, we're not really talking about what we expect the numbers to do, especially in the early days when you can have a lot of variability and where a lot of the day-to-day information is not really all that helpful, frankly. We have, however, committed to providing reasonably wholesome updates when we have the opportunity and certainly as the launch progresses. We are going to ensure that we give people access to the important information they need to make their own decisions as to how the launch is progressing. I'm not sure it's particularly helpful at this point to give really granular thoughts on how it might go, especially in the early days.
These things take a little bit of time to get started, and we want to give the team the opportunity to get out there and really start to have some high-quality interactions and build base here in the early days.
Okay. I might have missed this. Can you just talk payer mix and then also your expectations for adolescent use? I'll jump back in the queue. Thanks.
Sure. I'm glad to address your question on the payer mix. In HAE today, it's about 70% that are on the commercial payer side, the private payers, and then about 28% that is Medicare, 4% Medicaid, and then a single percentage point that is cash. That is what we see in the marketplace, and we would expect use of Ekterly would mirror that.
In terms of adolescents, it's well known that they have the longest delays in time to treatment, in terms of treatment proportion of attacks. There's a lot of unmet need there. Despite the fact that it's obviously a smaller subpopulation, we do think that the opportunity for adolescents to make use of this is really high, and we expect there to be a pretty significant level of enthusiasm for it.
Thanks again for taking the questions.
Thanks, John.
That concludes today's question and answer session. I'd like to turn the call back to Ben Palleiko for closing remarks.
Thank you all for joining us today, and thank you for being part of the journey so far. We do look forward to the next opportunity to provide an update on our progress with Ekterly. With that, we're off to work here, and we wish you all the best rest of the day. Thank you. Bye.
This concludes today's conference call. Thank you for participating. You may now disconnect.