Good morning, everyone, and welcome to the argenx ADHERE Trial Top-Line Results Conference Call. At this time, all participants are in a listen-only mode. To follow the presentation, we ask that you navigate the slides as directed by argenx management. There will be a question-and-answer session to follow. I would now like to introduce Beth DelGiacco, Vice President of Investor Relations and Communications at argenx. Beth, please proceed.
Thank you. Good morning to everyone on the call. Earlier today, we issued a press release summarizing our positive top-line ADHERE trial results. The press release and the presentation for today's webcast can be found on our website. On the call today are Tim Van Hauwermeiren, our Chief Executive Officer, Luc Truyen, our Chief Medical Officer, and Karen Massey, our Chief Operating Officer. Karl Gubitz, our Chief Financial Officer, will also be available for the Q&A session following prepared remarks. Before we begin, I'd like to remind you on slide two that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical development, regulatory timelines, the potential success of our product candidates, financial projections, and upcoming milestones. Actual results may differ materially from those indicated by these statements.
argenx is not under any obligation to update statements regarding the future or to conform new statements in relation to actual results unless required by law. I'll now turn the call over to Tim.
Thank you, Beth, and welcome to all who joined the call today. We are very happy to share with you the positive top-line results from our ADHERE trial of efgartigimod in patients with chronic inflammatory demyelinating polyneuropathy, or CIDP. Let's get right to the punchline. The study met its primary endpoint, showing a statistically significant reduction in the risk of relapse based on time to first adjusted in INCAT deterioration. The P value says it all. VYVGART HYTRULO is providing a clinically meaningful benefit for patients and importantly, a favorable safety and tolerability profile. It is consistent with the profile we are now accustomed to for VYVGART. These are outstanding results, and we hope they are the start of a paradigm shift in the treatment of CIDP. We made some bold decisions with how we designed the ADHERE trial.
It was the first of its kind in a disease that is complex and often misunderstood. We implemented several innovative components, which we hope will set a new standard for how CIDP studies are run, and we always put the patient first. Based on the outcome today, these decisions paid off. Slide four. Our mission at argenx is to transform severe autoimmunity. We want to raise the bar, and we have the precision tool to do it. With every study we run, we gain a new understanding of the underlying biology of autoimmune diseases and can ultimately create a new classification of those which are specifically IgG-mediated. We want to bring a similar revolution to how autoimmune treatments can meet the needs of patients. People living with autoimmune disease should not have to navigate a perpetual balance between symptom management and side effects.
Today, we feel we are on track with this ambitious mission. Today's news is not only significant for argenx, but a truly historic moment for the broader CIDP community. Patients and their supporters have waited a long time for innovation, and today we bring hope of a new treatment option that takes the full patient experience into consideration. The ADHERE study was the single largest CIDP trial ever conducted, enrolling 322 patients globally and uniting the community together in the collective pursuit for new treatment options. The underlying pathology of the disease is not well understood, and we've been able to generate a significant amount of translational data. We still need time to analyze the full extent of it, but importantly, we know today that IgG autoantibodies play a fundamental role in CIDP.
We hope by unlocking new biology insights, that we can provide greater clarity for patients and physicians around the CIDP diagnosis. Before we get to the detailed trial results, which will be presented by Luc, I would like to bring the patient into focus and discuss the unique challenges experienced by this population. Slide six. We have engaged with the CIDP community for the past several years, carefully listening to both patients and their supporters to learn more about the challenges they face with their disease and with currently available therapies. It became abundantly clear there is a strong need for safe and effective therapies that come with significantly less treatment burden. As a chronic progressive autoimmune disease, people living with CIDP face a lifelong journey. This starts with diagnosis, often coming after years of uncertainty, especially with more atypical cases. CIDP is an incredibly debilitating disease.
We have case studies of patients who deteriorate to the point of immobility within three months of diagnosis. 30% of patients, if left untreated, end up in a wheelchair and may suffer balance issues and a constant fear of falling. They are often reliant on a walking device, which can be difficult due to the neuropathy in their hands associated with the disease. Even with the certainty of a CIDP diagnosis, patients face a future where they may lose their mobility and their independence, which contributes to high levels of anxiety and depression. This patient community feels alone and often misunderstood. While current treatments can manage symptoms, they often come with significant side effects or with a treatment burden of long and frequently administered infusions. It is with the patient experience in mind that we designed our highly innovative trial and are delighted with its positive results.
I'll now turn the call over to Luc, who will talk through the trial design and study results. Luc?
Thank you, Tim. Slide seven. I want to echo the sentiments you shared already today. These positive results represent a big moment for patients and hopefully the start of a long-awaited change to more targeted therapies. I want to thank the CIDP community for working alongside us and participating in this study. I also want to acknowledge our argenx team for their herculean efforts to run such a robust and high-quality experiment. We worked closely with leading CIDP experts to design ADHERE and used key learnings from precedent trials. The result was a thoughtful, innovative design that sets a new standard for future CIDP clinical trials. We started with a screening period to ensure we enrolled true CIDP patients into the trial. Misdiagnosis has been a common issue in prior trials, given the heterogeneous presentation of the disease.
We addressed this in our study with the CIDP Confirmation Committee, which required two independent expert reviewers to confirm diagnosis. The committee served its purpose, as 28% of patients screened did not meet the criteria for CIDP. Secondly, we confirmed patients with active disease and were not in remission. We did this by implementing a treatment withdrawal period, during which patients needed to demonstrate clinically meaningful worsening on one of three scales: INCAT, I-RODS, or grip strength. In total, 322 patients entered Stage A and VYVGART HYTRULO. To classify as a responder and advance to the randomized placebo-controlled Stage B, patients had to demonstrate evidence of clinical improvements or ECI by regaining what they had lost during the treatment withdrawal period on the same scale. ECI had to be demonstrated at two consecutive visits as confirmation of a sustained benefit from treatment.
221 patients responded VYVGART HYTRULO and entered Stage B. We randomized 1-1 to treatment or placebo in a randomized withdrawal approach. Patients were treated for up to 48 weeks or until they had a relapse, which was defined as a one or more point worsening on the INCAT scale from the Stage B baseline. This was an event-driven study, which ended once we had 88 total events across the treatment and placebo arms. The primary endpoint was the relative risk of relapse or the hazard ratio based on time to first adjusted INCAT deterioration of one or more points. We continued to enrol patients into the trial until we reached 88 events. This means we have patients ongoing across the study at this time, including 18 patients in Stage A.
In total, we had 91% of eligible patients roll over to the open-label extension to VYVGART HYTRULO. Slide eight. The patient population we have here was representative of the real-world CIDP population and on par with past trials. We enrolled patients who had been on IVIG or steroids within the past six months, and also treatment-naive patients, including both newly diagnosed and patients who had been off treatment for the last six months. Slide nine. In Stage A, we saw a 67% response rate overall. We were very happy with this number, which is close to what is observed with PLEX clinical practice. This number also includes the 18 patients ongoing in Stage A at the end of the trial, who were all counted as non-responders, although we never learned their responder status.
If you remove these patients from the equation, the response rate was 70%, as you can see on the slide. By design, all patients entering Stage A were required to show deterioration prior to VYVGART HYTRULO, ensuring they had active disease, so we were not surprised to see a subset of early dropouts who could not wait for the drug to take effect. In particular, we saw a higher rate of dropouts among the prior IVIG-treated patients in the first two weeks. This trend was also observed in prior IVIG studies. We looked at the response rate across all patients who were able to receive four injections of VYVGART HYTRULO, thus achieving the full IgG lowering effect. Among this group of 275 patients, we saw a response rate of 78%.
This is probably more reflective of what would be happening in the real-world setting. Overall, we saw good responses across all subsets and consistency across all efficacy scales, regardless of prior treatment. Of the patients who responded, mostly it's on the INCAT scale, though all three scales moved in the right direction. Not only do the data from Stage A establish the competitive profile of VYVGART HYTRULO from a response rate perspective, they also provide compelling evidence that CIDP does in fact have a significant IgG-driven component, thereby furthering our understanding of the disease biology significantly. Here we have the Stage B data. We met our primary endpoint, demonstrating a highly significantly lower risk of relapse with VYVGART HYTRULO compared to placebo, based on the time to first adjusted INCAT deterioration.
The robust p-value you see is driven by a hazard ratio of 0.39, indicating that VYVGART HYTRULO reduces the risk of relapse by 61%. The Kaplan-Meier curves are also very compelling. We see fast, clear separation between treatment and placebo groups, which is then maintained over the course of 48 weeks. We actually couldn't calculate the median time to relapse for the treated arm because the median was never reached. We were able to calculate relapse rate at various time points. At week 24, we see a delta of 28% between active and placebo, and at week 48, a delta of 26%. Similar to Stage A, we saw consistent benefit demonstrated across prior treatment subsets. Slide 11. Our secondary endpoints provide more insights into functional deterioration based on I-RODS and grip strength.
The results are similar to INCAT deterioration, we see that VYVGART HYTRULO significantly reduces the risk of CIDP disease progression compared to placebo, based on the time to first I-RODS deterioration of four or more points. We saw a numerical difference on the I-RODS improvements from Stage B baseline favoring treated over placebo patients. Also, VYVGART HYTRULO patients had a mean improvement of 7.7 points on I-RODS and 12.3 kilopascal on grip strength in Stage A, which was maintained in Stage B by treated patients and lost by placebo patients. In conclusion, this shows the magnitude and durability of effect. VYVGART HYTRULO demonstrated a favorable safety and tolerability profile in ADHERE, consistent with prior studies and with the approved label for VYVGART in gMG.
Most adverse events were considered mild to moderate. No new safety signals were identified up to 48 weeks of weekly treatment. We observed quite low incidence of headaches and infections. Both were well-balanced across the treated and placebo arms. The most common adverse event was injection site reactions, which were seen in 20% of patients in Stage A, reduced to 10% in Stage B. Overall, the ADHERE data presents a very strong value proposition for patients. VYVGART HYTRULO was well tolerated with few side effects. We saw PLEX-like response rates in Stage A, which were sustained in Stage B. This represents a real change from what is currently available for patients, providing the first new compelling benefit-risk proposition for CIDP patients in 30 odd years.
I will now turn the call over to Karen, who will share how these data translate into a clear opportunity for CIDP patients.
Thank you, Luc. Slide 13. It is incredibly exciting to be here today to share these top-line results and how we hope to bring this innovation to people living with CIDP as quickly as possible. We believe with these exceptional data that we can ignite a real paradigm shift with our precision treatment, which is the first innovation in the treatment of CIDP in 30 years. Current treatments come with many trade-offs, and now is the opportunity for transformative change. As Tim mentioned, our mission is to redefine what well-controlled means for patients and to raise the bar on what a treatment can offer, taking into account the full patient experience, efficacy, safety, and the burden associated with administration. Starting with efficacy, we now have this answer. The ADHERE data shows that VYVGART HYTRULO is effective in treating CIDP in a broader patient population.
We demonstrated up to a 78% response rate in Stage A and significant clinical efficacy in Stage B, with 61% reduction in the risk of relapse and sustained response over 48 weeks. As Luc noted, VYVGART HYTRULO has also demonstrated a highly favorable safety and tolerability profile. We cannot underestimate the significance of safety and tolerability when it comes to patient and physician expectations. We want to shift away from CIDP patients having to balance side effects in order to attain effective disease control. Lastly, chronic treatments can come with long hours in the infusion chair and a lot of organization to schedule and keep track of appointments. The third part of the value proposition of VYVGART HYTRULO is the speed of administration, with a 30-90 second injection. In here, 91% of patients chose to stay on VYVGART in the open label extension.
I believe this is proof of the value proposition to patients of this highly innovative new treatment option. People living with chronic diseases want more days when they're not constantly reminded of their disease or having to manage their lives around receiving their next treatment. They want time back to refocus on the things that make them happy. This is our goal for the 16,000 CIDP patients in the U.S. and more broadly around the world. Slide 14. Our team has been building leadership in the neuromuscular space over the last several years across early discovery, research and development, and more recently, commercial. We've invested in broad capabilities, strong relationships, and global infrastructure because we plan to leverage what we've built for MG across many other neuromuscular diseases, including CIDP. The future of our neuromuscular leadership extends beyond gMG and CIDP with VYVGART.
We are also evaluating the potential of our first-in-class FcRn blocker in myositis and are advancing EMPA in MMN and ARGX-119 in congenital myasthenic syndrome and ALS. We will take the learnings from our neuromuscular franchise and apply them to our expansion in hematology, dermatology, and rheumatology. Today is one important step in reaching our bold vision to transform autoimmunity globally. Slide 15. Last, before I turn the call back to Tim, I want to talk about our team and our ability to consistently execute. With these top-line results from ADHERE, we have an impressive track record, with four, four successes from our VYVGART proof of concepts and registrational trials. For a first-in-class novel mechanism in action, this is impressive.
By starting with a strong biology rationale, focusing on the greatest unmet needs for patients, and designing innovative trials, we are unlocking new disease biology and transforming outcomes. Our first product, VYVGART, was approved in six regions within 18 months, most recently in China. We still expect more by the end of the year. We generated $401 million in global product revenues of VYVGART last year and $280 million in the first quarter of this year alone. VYVGART HYTRULO is off to a strong start in the U.S., with product in the channel and enrolments already coming in. We're a team that continues to dream big and deliver on its promise to patients. Tim?
Thank you, Karen. Our vision is very much alive. I'm so happy to be here today to deliver the good news on CIDP. This is a momentous day for patients, physicians, and for argenx. It is time for transformative change, and we are ready to deliver. Before we open the call up to your questions, I want to sincerely thank our hardworking and talented team for their passion and dedication to the important work we do on behalf of patients. Our success would not be possible without each and every one of you. Thank you. We will now open the call for Q&A.
At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We ask that you please limit yourself to one question and then rejoin the queue for further questions. Your first question comes from the line of Danielle Brill from Raymond James. Your line is open.
Hi, guys. Good morning. Congrats, and thank you so much for the question. I just wanted to follow up on your launch strategy. So with an estimated 16,000 addressable patients in the U.S. and these data in hand, is it fair to assume that CIDP represents a similar size market as MG? Where do you see VYVGART ultimately fitting into the CIDP paradigm? Thank you.
Thank you, Danielle. Thanks for being with us today. We really appreciate it. Of course, we were waiting for these top-line data to understand, you know, what is the power of VYVGART, which we have in our hands, and clearly these are stellar data. This will feed straight into the commercial strategy. Today is really about top-line data, but I'm going to invite Karen to maybe share some initial commercial thoughts. Karen?
Yes. Thank you, Tim, thanks for the question. In terms of comparing this opportunity to MG, the way that I think about it is, in both of these areas, there's a huge unmet patient need for better treatments and for more innovation. In the past, when I've talked about the commercial opportunity in CIDP, I really talked about the value proposition through the lens of our efficacy, safety, and tolerability, and then treatment burden. You know, we've always known if we take treatment burden, we have a 30-90 second injection versus the standard of care for CIDP today, where patients are tied to the infusion chair and have a significant treatment burden. We have a clear advantage there.
In terms of tolerability and safety, we expected to see in the data similar to our real-world experience in MG. That's exactly what played out. We really believe that from a patient experience perspective, the tolerability for VYVGART is significantly better to the options that they have available today. The big question for us in terms of commercial opportunity was always on the efficacy. Where was that going to land? Now we have that data. You've heard it a few times, but I think it's worth repeating that the broad efficacy in the response rate of up to 78% of patients demonstrating that it's clearly IgG-mediated disease.
A significant response rate, 61% relapse reduction over 48 weeks. That separation was sustained over 48 weeks, that you can really start to think about how this is truly transformative for patients. That's, that's the way we think of the commercial opportunity, that we'll be able to change the treatment paradigm. We'll be able to go broad, and we'll change that experience for patients. In terms of sort of size versus MG and all of those, that will come in time. We have a lot of market research to do, a lot more workup to do, and we'll share that in due time, our opinions on that.
Thank you, Karen.
Your next question comes from the line of Tazeen Ahmad from Bank of America. Your line is open.
Hi, good morning, and congratulations on pretty flawless data. Really well done. I just wanted to follow up on thinking about some more differences between gMG versus CIDP. Specifically, how are you thinking about the dosing frequency that'll be needed for CIDP patients versus what you're seeing so far for gMG? Can you just remind us what the next steps are in preparation for application for approval? Thank you.
Thank you, Tazeen. I will give the second question to Luc, who can inform us about how we think about next steps. From a dosing point of view, remember that in the ADAPT study for myasthenia gravis, we went into individualized dosing, so one cycle consisted of four consecutive infusions of the product, and then we could basically, tailor the cadence of the cycles to the individual need of the patient. For CIDP, we really wanted to hit it hard. We went for weekly dosing in the first portion of the trial, and then for those people in the open label extension who are doing very well on drug, there is the option to choose for every other week dosing. From a milligram consumption point of view, that would basically bring these patients on par with an MG patient on an annualized basis.
Maybe, Luc, you want to talk about next steps?
Yeah, sure. Of course. The first step is to prepare for that interaction with the regulator so that we can show and discuss the data with them and talk about next steps. Internally, we are starting preparations for to submit an sBLA.
Thanks, Luc.
Your next question comes from the line of Derek Archila from Wells Fargo. Your line is open.
Hey, yeah, good morning, let me add my congratulations on the data. I'm just kind of curious, you know, I guess, what does it mean biologically for the patients that actually did not respond in Stage A? I know there's about 20% if you take into account all the patients receiving four doses. I'm just kind of curious, do you just treat them longer to see if they eventually respond, or do you think there's something else that's going on there? Thanks.
Thank you, Derek, and thanks for joining us today. I think the explanation to the question is relatively straightforward. Luc, maybe you want to go first into trial design?
Yeah. When this trial was conceived, there was actually quite not much known about the actual role of IgGs in the disease. We therefore had to make sure that on the clinical side, we had a homogeneous population very representative of CIDP, which is why we had that CIDP Confirmation Committee. We wanted to make sure patients deteriorated, and all of them did. That went into stage A, we have the response rate you see. Why is it incomplete? I think part of that has to do with that it's a complex disease. Part of that has to do with some of the dropouts we saw early on in Stage A, because of patients that were going down faster on after the withdrawal.
I think actually the rate that we do observe is quite stellar, so we're very happy with that. The fact we don't reach 100%, which that would be, of course, fantastic, has to do with the variability of the scales, the subsets of patients, and so forth.
Thank you, Luc. Thank you, Derek.
Your next question comes from the line of Yaron Werber from TD Cowen. Your line is open.
Great, thanks so much, let me add my congrats. Data's really terrific and exactly what we're all hoping for. I have an interrelated question. In the open label extension, you're testing now [Q] other week, you've already pretty much are showing nice flattening of the curve. You didn't even hit your progression yet at 48 weeks. Do you think you could potentially dose every two, every other weeks and show maintenance? Secondly, I believe even Hytrulo is going to be sort of capped under the value-based agreements at around $225,000 or so per year. Obviously, you're dosing initially weekly, which is going to double sort of the price. Should we sort of assuming our model, that you'll have the same VBAs with the same sort of cap on pricing? Thank you.
Thanks, Yaron. I will leave it up to Luc to comment on the every other week dosing and whether that would represent a potential maintenance offering. It's, of course, still very early because the overlay is ongoing once we speak. Then maybe, Karen, you can share a few thoughts on, you know, our relationships with the payers. Maybe, Luc, you go first?
Yes, thanks for that question. It's something we're also very interested in, to see what happens in the long term in our 1902 study. Those data are being accrued. We have a sub-study in there where the patients can go to biweekly dosing. I think we will be very interested to see whether we come at, to an outcome similar to gMG, where indeed, based on intrinsic disease activity, you can start tailoring dosing frequencies.
Yeah, perfect. Thank you, Luc.
Karen?
Yes. Yeah, great question. It's one of those that's on our mind as well. It's really too early for us to share the exact approach that we'll be taking. That's the work that we'll be doing over the coming months. You're right in thinking about it, we'll take the same or a similar approach that we did with MG, which is an innovative value-based approach. Through that value-based approach that we've taken with MG, we've developed, I would say, really strong relationships and partnerships with the payers. Payers recognize the value that VYVGART is bringing, to the healthcare system, and you can see that in the coverage levels that we have. I think we've developed real credibility there.
We'll take a similar approach, and we'll focusing on access for patients, and we'll be able to share more with you over the coming months around what that specifically looks like.
Thanks, Karen.
Your next question comes from the line of Yatin Suneja from Guggenheim. Your line is open.
Congratulations to the team, and thank you for taking my question. The question I have is more around the breadth of response. It seems like the response was similar, whether you look at naive patients or pre-treated. Can you maybe just articulate a little bit more what additional you might be seeing? Is the onset different? The reason I ask is, and I understand the cross-trial comparison, PATH only had pre-treated patients. You guys have 35% of patients that were naive, so, and d espite that, you were able to hit the similar hazard ratio, so the results are truly remarkable. Some articulation there would be very helpful. Thank you.
Thank you, Yatin. As a start, I would like to say that this trial, you know, was the biggest ever in CIDP. It's a truly global trial, and we were able to enrol a real broad, representative CIDP patient population, so we have all subsets represented. The good news from the top-line data is all these patients, regardless of their prior therapy status, had the same right to respond to VYVGART. Exactly how the kinetics and the dynamics work out for the different subsets remains to be seen. It's subset of ongoing data analysis, and we will get back to you with more granular data at one of the upcoming clinical conferences. Stay tuned.
Your next question comes from the line of Thomas Smith from Leerink Partners. Your line is open.
Hey, guys. Good morning. Thanks for taking the questions. Let me add my congrats on the stellar data here. I was just wondering if you could provide a little more color on the screening and adjudication process that you used to confirm the patient's CIDP diagnosis. 26% screen fail rate was notably lower than what you presented previously. What do you think drove the delta there? How do you think about identifying these CIDP patients in the real world? Thanks.
Thomas, thank you for the question. I think you're hitting on an important point. The feedback of the community actually is that not only have we reclassified CIDP as a true IgG-mediated disease, we have also set a whole new standard for the way people will conduct CIDP clinical trials. Maybe, Luc, you want to inform us a little bit in more detail on the adjudication?
Yes. The way it was set up was that patients who passed first screening items, and therefore the next dependent question was, do they have probable or definite CIDP according to the 2010 criteria, was then posed to an external panel of nine experts, who got sent in pairs, the necessary information to make that determination. Two experts looked at the same case, if they were concordant, patient was declassified as a definitive or a probable CIDP patient and could proceed down the path of the study. If there was a non agreement, then the chair finally ruled. That worked very well. If you now look at,
Indeed, we screened out 28% of the totally screened population out for having not CIDP, according to these rules. We ended up with a highly representative population in our trial. From our point of view, this really worked very well.
I think, Luc, if I may add, the misdiagnosis number went down from 50% to 28%, where we think there was a learning curve with the PI community throughout the study, right?
Yeah.
Your next question.
Thank you for the question.
Your next question comes from the line of Myles Minter from William Blair. Your line is open.
Thanks, congrats on the data. We've spoken with a few just experts, predominantly U.S. based, who think that IVIg is pretty sticky, and they'd be reluctant to switch patients if they were having a response. I guess, do you think that this data changes that mentality either now or over time, or is your primary commercial focus gonna be on newly diagnosed patients or Ig refractory patients? A quick clarification, just wondering why there was 214 responders in part A, but there was 221 patients enrolled in part B. If you could just clarify that. Thanks.
Maybe, Luc, you very quickly take question two.
Yeah.
Karen, you take question one.
Mm-hmm.
Yeah. I mean, that discrepancy, as happens often in trials, was actually driven by some, a protocol violation of people who actually did not meet the improvement criteria in that period. That's the reason for the discrepancy happens in trial.
Mm-hmm. Thanks, Luc and Karen?
I'll answer quickly. I mean, we have more work to do on the commercialization plan, but what I will say is we have incredible results today that. We laid out how we really think they're differentiated from anything else that's on the market, including IVIg, the first innovation in 30 years. We believe that we can provide a better value proposition for patients. How that plays out in the commercial market with IVIg on label. As you said, with patients, some patients well controlled, we'll have to see and do more, we'll do more research on that, and we'll come forward with how we think the market's going to break down as we have more insight.
Thanks, Karen.
Your next question comes from the line of Alex Thompson from Stifel. Your line is open.
Hey, good morning, and let me add my congrats as well. I just wanted to talk about self-administration quickly. You know, how does CIDP patients compare to MG patients in terms of muscle weakness or other issues that FDA flagged in terms of the self-administration versus HCP administration? I guess, what are your expectations around having a prefilled syringe available with the CIDP launch? Thanks.
Hey, Alex, thanks for joining us, and thank you for the question. It's of course, premature to make any statement about self-administration for CIDP because we still need to engage with the regulator. There is no approval, there is no label. Clearly, this is again another disease, you know, involving muscle weakness. I think advancing the prefilled syringe is a strategic priority for the company, which could well read across multiple indications. Stay tuned, we will keep you informed on progress on that front. Thanks for the question.
Your next question comes from a line of Akash Tewari from Jefferies. Your line is open.
Good morning. Thanks so much, really great data. It looks like there was a lower progression rate from Stage A to stage B in prior IVIg patients than the naive and steroid-refractory population. Can you comment on what contributed to the higher dropout rate there, and maybe how that dropout rate compared to the past study, which also had a disease-worsening component? I think, Tim, maybe just stepping back, you've stated that VYVGART will go after 15 indications by 2025, but then at the same time, the IRA's accelerated development timelines across the industry. Outside of what I'm sure would be an attractive takeout price, is there any advantage of having VYVGART in the hands of, let's say, a large cap pharma, in terms of getting VYVGART onto the market and those indications more quickly.
What could an outside party potentially bring to the table? Thank you.
Yeah, thank you, Akash. Let's start with question, one, first, maybe, Luc, you want to briefly comment on some of the IVIg dropouts?
Yes. Yes, indeed. Again, we have to remind that in the trial, patients were required to stop their current treatment and then show deterioration on the running. This stress test was aimed to ensure that we had active disease, and we actually thank the patients for their willingness to do this, to evaluate this new treatment. By consequence, it isn't actually a surprise to lose some patients early, in particular, if you have very active or unstable disease, and also observed more with IVIg. The difference in response rate in Stage A is affected indeed, by losing a proportion of IVIg patients early in that stage, even before they were able to get to the four injections or more significantly exposed efgartigimod.
In fact, in the protocol, we had built in a safety mechanism that if deterioration was too fast, too steep, that they would be, quote, unquote, "rescued." This phenomenon is actually even observed in trials where you switch between forms of IVIg, and in fact, in the past, in this, along these lines, the dropout rate was about 17%. It's not uncommon to see this. It's a factor of the study design.
Not unexpected and in line with historical trials. On IRA, Akash, tell me if I have it wrong, but I think you would be hard-pressed to launch more indications and roll them out faster than what we did, right? I think nobody believed us in 2019 when we said we would be in 15 indications by 2025. Watch it, we will be there. I think, you know, having this amount of approvals in just 18 months' time, no one, I think, could have reached MG patients faster than what we have been doing around the globe. I think this company is hyper-focused on execution, and I feel we're very well positioned to take the maximum benefits of the VYVGART molecule. Thank you for the question.
Your next question comes from the line of Vikram Purohit from Morgan Stanley. Your line is open.
Hi, good morning. Thanks for taking our question. We just had a broad follow-up question on commercial strategy. To what extent can you leverage the sales infrastructure currently in place for VYVGART and myasthenia gravis? Do you think you'd need to strengthen the sales force presence for CIDP versus MG? If so, by how much do you think the scale would need to increase here? Thanks.
Yeah, thanks for the question. When the strategy was laid out for MG, a few years ago, the strategy was to build the infrastructure, including the sales force, as you mentioned, but patient support and others, to invest with a line of sight to the future indications that could be coming.
We have invested with that line of sight, and we have a stellar team in place, and all of the infrastructure and relationships, to really take a leadership position in neurology. Now, when we see this data, obviously, it is, we see the opportunity, for real differentiation in the CIDP market. What that means for our commercialization, we need to work out over the coming months. We'll certainly be able to leverage all of the great work that's already been done in MG.
Thanks, Vikram.
Your next question comes from a line of Joon Lee from Truist Securities. Your line is open.
This is Austin dialling in for Joon. Congrats on the impressive data, and thanks for taking our questions. A couple questions from us. What would you ascribe the success of ADHERE in CIDP, the innovative trial design or efgartigimod's fundamentally differentiated MOA?
Just curious why you think efgartigimod succeeded where rozanolixizumab failed, and if this is a positive read-through to other competing drugs in development for CIDP? How does positive data in CIDP change your perspective on future indications for efgartigimod? Are there some high-risk, high-reward indications you were contemplating that you think are now more within grasp? Thank you.
Thank you for both questions. Luc, why don't you take question one? I will happily take question two.
Yes. it's actually a combination of the two, huh? VYVGART was the first new mode of action that was going to be evaluated in over 30 years in this disease. We wanted to make sure that we were able to tease both the efficacy signal and potential of VYVGART, as well as the safety signature, as effective and efficiently as possible. That's why the design of this trial contributed to teasing that out, because, A, we confirmed that people indeed had CIDP with a selection committee. We stress-tested them to make sure they had active disease, and therefore, would benefit from. We thank the patients for going through that.
In the first counter challenge with VYVGART in all patients, we showed we could bring them back up, the efficacy scale and then kept them there. I think it's therefore, to your question, it's both. A unique mode of action tested for the first time with a very unique design that allows us to really establish the risk-benefit.
Thanks, Luc. On the second question, we think this validates the approach which we systematically take to indication of new selections. We always start from biology first. I think the way we unpacked it for CIDP is the same way as we do it for other indications, definitely a validation for our approach. Although I have to be honest and say that each indication will come with its own clinical trial execution risk, it remains a clinical experiment. Now, these data increase further the conviction we have in our molecule. It's strengthening our belief this is a unique once-in-a-lifetime opportunity, we are going to maximize that potential. Thank you.
Your next question comes from the line of James Gordon from JP Morgan. Your line is open.
Hello, thanks for taking the question. James Gordon, JP Morgan. It was just about CIDP market segmentation. My question is, what proportion of currently treated IG patients do you think are under-dosed on Ig and not getting enough efficacy or have tolerability issues? What proportion of CIDP patients do you think are actually new to therapy each year, so that would be addressable if you were to go after naïve patients?
I'm blanking on the. Thank you, James, for the question. I'm blanking on the number of newly diagnosed people. I don't know the incidence base, because this is really a problems indication. On your second question, I think undertreatment would be typically an issue outside of the United States. We know there are sometimes supply issues for IVIg outside of the United States. People would complain that sometimes, you know, they're being rationed on their IVIg or deprived of IVIg and having to go back to steroids, which of course, is a nightmare. So our understanding is that about 80% of the patients in the States would be on IVIg, and that is, of course, a very attractive patient population to pursue. Thanks for the question.
Your next question comes from a line of Rajan Sharma from Goldman Sachs. Your line is open.
Hi, thank you for taking my question. It's just kind of go back on the commercial infrastructure required for CIDP. I guess the question is, based on the data that you've seen, which sounds like it may have been stronger than you were originally expecting, do you think there's any change to the level of investment that you'll make behind the product's launch? Thanks.
Thank you for the question, and maybe, Erica, you want to have it, rather?
Absolutely. I think you're right in saying that whether the data is stronger than we expected or whether we can just say that the data is incredibly strong and demonstrates a really strong value proposition to patients. I don't think it changes our commercialization approach, but what it does is open the door for us to really go to the next level of detail on what that commercialization approach needs to be, what the patient populations are, and how we might go about the education that is needed in the market. That's the work that we'll do now. Now that we have the data, we can peel that onion one layer more and do that additional workup.
Thanks, Karen.
Your next question comes from a line of Samantha Semenkow from Citigroup. Your line is open.
Hi, thanks very much for taking the question, and let me add my congrats on the data today. Are you able to share with the average or even the median number of doses that patients received in Stage B before relapse? I know it's early days, but have you seen any patients that rolled over into the open-label extension that had relapsed on VYVGART respond to retreatment?
I can talk about the. That's one of the problems we have. We don't get to a median relapse, so the number of doses to be calculated based on median time to relapse for efgartigimod, we cannot do.
That is stage B, right, Luc?
Stage B.
I think the question is to Stage B, but the answer is short, right?
I think, and more data will need to be presented at the clinical conference. It looks like we see the VYVGART signature again. You know, it's typically fast in its onset of action, or in the first weeks, you see a significant portion of patients respond. You continue to respond, you know, up to the 12 weeks, right? Stay tuned. More granular data will follow.
What was the second question, Luc? Do you remember?
No, because I've switched Stage B and A.
Samantha, could you repeat the second question, please?
I think the second question was, have you seen any of the patients that have relapsed on VYVGART respond to retreatment in the open-label extension?
That we are definitely looking forward to evaluate because, I think that would be talking to the potential just fluctuation that happened in the disease and by how we operationalize relapse, made people be defined as a relapse, but they were actually still potentially benefiting. We have to look at that in the 1902 data readout.
Yeah. That will be subject of the open-label extension data readout. It's a bit premature for us to comment on it, right? We really focus now on the top-line data over here. Thank you.
Thank you, Samantha.
Your next question comes from the line of Allison Bratzel from Piper Sandler. Your line is open.
Good morning. I'd like to add my congratulations, and thank you for taking the question. Just a question on IVIg switching. I guess, is it your sense that neurologists would be looking for additional clinical data that can help inform the optimal way to switch patients from IVIg or steroids to VYVGART in a, in a real-world setting, you know, that is without the washout period and disease worsening that was required in ADHERE? Is this data enough to drive switching directly from one treatment to the other? Thanks.
Hey, Allison, thanks for joining us in the call today. I'm going to be short in my answer. I think this is an incredibly large and detailed study. I think we are equipped with tons of data to go and effectively compete. I don't think you would need a switch study. We have a lot of data here to convince treating physicians, you know, on the benefits of VYVGART. I think we're very well equipped to compete. Thank you for the question.
Your next question comes from the line of Joel Beatty from Baird. Your line is open.
Hi, this is Benjamin on for Joel. Thanks for taking the question. Was the trial powered to show a benefit on the different subgroups, such as different prior treatments and lines of therapy?
No, the powering of the trial at the time was started, was done to detect a hazard ratio of 0.5 difference with 90% power. That was the
In the total population, right?
Oh, Yes.
Yeah, yeah. No, Benjamin, there's no power in the study to go for subset. We did stratify, right, Luc, in the study?
Yes.
For prior medication.
Yes.
We will be able to break down the data and show them at the clinical conference later.
Correct.
Thank you, Benjamin.
Your next question comes from the line of Douglas Tsao from H.C. Wainwright. Your line is open.
Hi, good morning, and thanks for taking the questions, and congrats on the data. Tim, you mentioned in terms of dosing, a desire to hit CIDP harder with the weekly dosing. I'm just curious, what the sort of, or was there a biological rationale for that, or did you just see a higher bar just given the sort of entrenchment of IVIg and just wanted to really maximize efficacy? Do you see an opportunity for sort of a customized dosing regimen in CIDP? Then just quickly a follow-up, and then another question. I know you've said that you saw improvement in INCAT and I-RODS in Stage A very quickly. I'm just curious from at what point did you really start to see a meaningful separation in the first? Thank you.
Yeah. Thank you, Douglas. I'll give question two to Luc in a minute. On question one, I think we can only, you know, talk about the theory. From myasthenia gravis, I think people spoiled because not only did we know the identity of the autoantibody, we also knew the linear correlation between reduction in autoantibodies on the one hand and delta on an ADL scale on the other hand, and we had it from the immunoadsorption and the plasma exchange literature. For CIDP, we had a very strong hypothesis. It had to be IgG- mediated for all the reasons we called out earlier, but there was no such correlation known. In absence of such a linear correlation, I think you go step by step, right?
You first test the hypothesis, it's IgG- mediated, and therefore, we pushed VYVGART to its maximum PD effect, which, by the way, is comparable to plasma exchange. Now that we have convincingly shown efficacy and the IgG nature of the disease, we can start to think about spacing out dosing. Mind you, that in the real world, also IVIg, you know, is individualized to a certain extent, both from a dose and a dosing frequency point of view. I would not be surprised that in the real world, VYVGART patients would also be able to do that. Luc, do you want to comment on question two?
Yes, thanks for the question because it also, for the prior colleague, allows me to rectify my misstatement on the Stage B and really answer for Stage A. There's a bit of an artifact in Stage A because by protocol, we only wanted to look at the early clinical improvement, established clinical improvement, after four doses of VYVGART. We only opened that box, so to speak, at week four. From that time on, when we do that, we see that there's 40% of people that qualify as a responder at that time already. That's very going to be very close to the median if you wait a bit longer. Also over the subsequent 12 weeks, we saw a ever-increasing line to the ultimate 67% of improvement.
Thank you, Luc.
Your next question comes from the line of Gavin Clark-Gartner from Evercore ISI. Your line is open.
Hey, thanks. Let me also add my congratulations on the data. I'm just wondering, for the patients who had received prior IVIg in your trial, what was the average monthly dose of IVIg that they were receiving? What does this dose correspond to in U.S. net price per year? Thank you.
Thanks again. The only thing we know about the use of IVIG is that, you know, it's typically between 0.4 and 2 grams per kilogram, which is given, you know, in one or two consecutive days, and then you need to repeat that infusion, you know, at every, you know, few weeks. There is no historical data, right, which we collected in the trial about the prior history of these patients. We only have information about the last six months on therapy. Okay? Now, on price, of course, maybe, Karl, you want to talk about some of the homework with this, a typical IVIg cost could be in the United States for a CIDP patient.
Yeah, we've done some market research. We will continue to do more market research as we dig into this. The range seems to be really broad, anywhere between $100,000 and $400,000 annual cost for IVIg in the US.
Thanks, Karl.
Your next question comes from the line of Charles Pitman-King from Barclays. Your line is open.
Hi, thank you very much for taking my questions, and congrats on the data. Two small ones for me. Just, I'm trying to dig into some of the baseline characteristics. I'm just noticing the time since diagnosis is slightly shorter for patients in Stage B and Stage A. If you could give any more insight into why that's the case. Just secondary question. One secondary endpoint of yours is doesn't appear to be statistically significant when looking at the improved function level, so the IRLS improvement of at least four points. Just wondering how we should think about this and what impact that may have on physicians' reading of this data. Thanks.
Look, maybe you want to comment on time from diagnosis between Stage A and Stage B?
Yes, we can of course speculate, but it's kind of a natural assumption that the longer you have disease, you're more difficult to treat, and thus may be less likely to respond in Stage A, which is an observation not unique to CIDP. We saw the same with MG and also ITP, both also progressive diseases. That's probably contributed to that.
On your other question, in hindsight, and it's always easy to speak from hindsight, that secondary endpoint may not have well been well chosen because there's no durability factor in there. You know, as soon as you hit it once, you qualify, and there's also no measure of the amplitude of the benefits to distinguish between active and placebo. This is not a very useful secondary endpoint. We did want to show it in full transparency because that's how we operate. You know, these were pre-specified endpoints, and we all report them to you. Thanks, Charles.
Your next question comes from the line of Emmanuel Papadakis from Deutsche Bank. Your line is open.
Thank you for taking the question. Perhaps just to follow up on how you think this data gets implemented clinically. How will doctors identify potential responders, and how will you indeed help them do that, given if we take into account the screen outs before part A and the 20%, 30% non-responders in part A, it means somewhere between half to two-thirds of patients actually respond. Any biomarker work you're doing, any way you think doctors go about trying to think about which patients might actually be receptive to FcRn therapy? Then just a quick clarification, if I may, on the injection site reactions. You said 10%. I assume that's a blended rate because your slide on safety shows 14%, just above 14% for VYVGART.
If you could just confirm that is the case and the mix of grades, I think they're all grade one, two, but the mix would be helpful. Thank you.
Thanks. I will give question two to Luc. Question one is very simple. Just like in MG, just like in ITP, just like in pemphigus, what we see is a VYVGART signature in terms of, you know, speed of onset. It would not be too difficult for a treating physician to figure out, you know, whether a patient is going to respond to VYVGART. You will typically find it out in the first few weeks on treatment. I think that's going to be very straightforward. Luc, do you want to comment on?
Yeah.
Question two?
The 14.4% on VYVGART in Stage B is indeed a blended rate across all the adverse event terms that roll up. The frequency is actually lower than we've seen before, and indeed, they were mostly grade one and two.
Thanks, Emmanuel. Thank you.
Ladies and gentlemen, this does bring us to the end of our question and answer session. This concludes today's conference call. We thank you for your participation. You may now disconnect.