argenx SE

XBRU:ARGX

Earnings Call Analysis

Solid Growth and Strategic Pipeline Advancements

In Q1 2024, the company achieved solid revenue growth with $413 million in total operating income, up 83% from the prior year. The growth was driven mainly by a 34% increase in U.S. patients and 46% in Europe for VYVGART, the company's leading product. Operating expenses were $506 million, slightly lower than the previous quarter. The company is preparing for its CIDP drug launch following promising Phase III data, positioning itself for sustained growth. Financial guidance for 2024 remains unchanged, with a strong balance sheet boasting $3.1 billion in cash and equivalents.

Strong Revenue Growth and Patient Reach

The company achieved remarkable revenue growth, with an 83% year-over-year increase in product net sales, reaching $398 million. This success is attributed to expanding patient reach, particularly in the U.S. where VYVGART Hytrulo saw a 34% patient increase. Notably, 50% of new patients were previously on oral treatments. Additionally, international markets like Europe saw a 46% growth in patients, driven by successful launches in Italy and Spain, and patient uptake in Asia, particularly in China, where 2,700 new patients started treatment due to VYVGART's inclusion on the NRDL.

Cost Management and Investment in Growth

Operating expenses amounted to $506 million in the quarter, reflecting a strategic investment in expanding the U.S. commercial infrastructure in preparation for the potential approval of CIDP treatment. Despite higher spending, the company remains committed to its long-term growth strategy. Increased SG&A expenses were attributed to investment in commercial efforts, notably expanding the customer-facing team in the U.S. and supporting geographical market expansions in Europe.

Pipeline Advancement and Clinical Trials

The company made significant progress in its clinical pipeline, with 48 ongoing clinical trials across 19 indications and three candidates. Key advancements include moving efgartigimod to Phase III trials for thyroid eye disease and Sjogren's syndrome, and empasiprubart's progress in MMN based on Phase II results. These trials aim to expand the label and address high unmet needs across various conditions, leveraging clinical data to drive R&D investments.

Strategic Decisions and Market Positioning

Strategic decisions included discontinuing development in ANCA-associated vasculitis (AAV) due to complex medication interactions, redirecting efforts towards systemic scleroderma, which presents a clearer clinical pathway. The company also plans to nominate additional indications for its assets this year. Focus remains on targeted investments and disciplined resource allocation to maximize long-term value creation.

Navigating Competitive Landscape and Pricing Strategies

Despite increasing competition in the gMG market, the company reported gaining market share among biologics, particularly with new patients transitioning from oral treatments. The broader market for biologics in gMG is still growing, and the company is well-positioned to lead within this space. In preparation for the CIDP launch, pricing strategies are being developed with an emphasis on value-based arrangements to ensure broad access and reimbursement.

Future Growth and Expansion Plans

The company's growth strategy includes expanding its patient base earlier in the treatment paradigm, regulatory approvals in new geographical regions, and expanding product labels to cover new indications. VYVGART subcutaneous forms and prefilled syringes are key innovations expected to drive growth by enhancing patient experience and widening market reach. Upcoming regulatory decisions in markets like Australia, Switzerland, and South Korea are expected to further boost global patient access.

Looking Forward with Confidence

The management remains optimistic about the future, citing strong underlying business fundamentals and a robust balance sheet with $3.1 billion in cash equivalents. Preparations for the CIDP launch are well underway, supported by successful bioequivalence and human factors studies. The company is confident in maintaining its growth momentum and continuing to make significant impacts in the autoimmune market through innovative treatments and strategic investments.

Earnings Call Transcript 2024-Q1

[Operator]

Good morning. My name is Rod, and I will be your conference operator today. I would like to welcome everyone to the call. [Operator Instructions] I'd like to introduce Beth DelGiacco, Vice President, Global Head of Corporate Communications and Investor Relations. You may begin your conference.

[Beth DelGiacco, executive]

Thank you. A press release was issued earlier today with our first quarter financial results and our recent business update. This can be found on our website, along with the presentation for today's webcast.

Before we begin, I'd like to remind you on Slide 2 that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical development, regulatory time lines, 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 those statements in relation to actual results unless required by law.

I'm joined on the call today by Tim Van Hauwermeiren, Chief Executive Officer; Karl Gubitz, Chief Financial Officer; and Karen Massey, Chief Operating Officer.

I'll now turn the call over to Tim.

[Tim Van Hauwermeiren, executive]

Thank you, Beth, and welcome, everyone. At the beginning of the year, we shared an ambitious plan to maximize patient impact over time through our 3 innovation horizons: First, bringing VYVGART to more patients by employing a multidimensional launch strategy; second, advancing our clinical pipeline, including empasiprubart and ARGX-119, which have potential across multiple indications with high unmet need; and third, leveraging our IIP to bring forward the next wave of novel targets to the clinics.

Today, I am pleased to share that our execution over the quarter puts us perfectly on track with this plan. Slide 4. Let's dive into some of our recent accomplishments, beginning with the team's success in delivering another quarter of solid revenue growth. We now have 7,500 patients on VYVGART and VYVGART subcu globally, which does not include China, where over 2,700 patients started on therapy in the first quarter alone.

This means we surpassed the 10,000-patient mark and we continue to reach new patients and prescribers each quarter, gaining market share among all MG treatments. We had 2 key drivers of revenue growth in the first quarter. First, we saw a 34% increase in patients on VYVGART subcu in the U.S. The majority of these patients were naive to VYVGART, so the subcutaneous product is expanding the market in the way we planned. Second, we saw 46% growth in patients on treatment in Europe, driven by strong demand in Germany and new launches in Italy and Spain.

And while it's still early days in the ITP launch in Japan, we are pleased to see patients already start therapy in our second indication. Looking ahead to next month and to the expected FDA decision for CIDP, we are making the right choices today with our gMG growth strategy that should serve us well for a CIDP launch in the scenario of an approval. We shared at the beginning of this year that advancing our prefilled syringe in both gMG and CIDP is a top priority for us and we have a positive update for you today. We have successfully collected all necessary data points from our bioequivalence and human factors study and are on track to file with the FDA by the end of June.

Our goal is to have the broadest product offering available to patients, recognizing that different patients and prescribers have different treatment preferences. With the prefilled syringe, we continue to innovate on the patient experience and will seek self-administration in the label, which we expect will help us reach patients earlier in the treatment paradigm. On the clinical front, we made important progress in advancing our next set of indications to Phase III and now have studies underway in thyroid eye disease and the anti-acetylcholine receptor antibody-negative gMG population. The seronegative study is designed to enable a label expansion into 15% of the broader gMG population beyond those patients we can serve today.

We are also advancing Phase III plans for efgartigimod in Sjogren's and empasiprubart in MMN based on Phase II results in both indications. And we still have additional data readouts ahead this year in PC-POTS and 3 subtypes of myositis, which [indiscernible] start registration studies depending on the outcome. The development of our earlier pipeline programs all remain on track, including patient studies of ARGX-119 and our upcoming INDs across 4 molecules as we rapidly work to advance the next wave of novel targets.

Slide 5. Last month, we presented important data to the neurologist community during AAN, furthering our confidence in the opportunity we have with VYVGART. In the absence of a cure, the best we can achieve for patients is deep and sustained functional improvements, not just managing symptoms, but getting to the heart of the disease to deliver a better outcome than patients have with current treatments. In gMG, this is minimum symptom expression or MSE and we demonstrate that across studies and various dosing regimens, approximately 50% of patients are able to achieve MSE. This comes without compromising safety. And in fact, we show that patients can meaningfully take steroids post the drug treatment, reducing treatment burden and improving the overall experience. We also presented new ADHERE data at AAN, specifically on function improvement, showing that some CIDP patients were able to improve more than 3 or 4 points on INCAT, which to put it into perspective, can mean the difference for a patient between being wheelchair-bound and walking without support.

Slide 6. During the first quarter, we announced our decision to advance efgartigimod to Phase III in Sjogren's disease following the outcome of the signal-finding RHO study. We are confident in moving forward based on the consistency of data across clinical and biomarker endpoints. This was a relatively small trial, just 34 patients, but one where we could look patient-by-patient at how these endpoints moved together. We had 2 objectives with the RHO study. First, to gain confidence to invest in further development; and second, to thoughtfully shape the Phase III study. We achieved both and see a clear opportunity ahead for VYVGART in this disease, where there is significant unmet need, specifically in those patients with moderate to severe systemic disease, who can experience dry eyes and mouth, fatigue, joint pain and even organ damage.

Slide 7. We are leading this new field of medicine with FcRn. And at the end of last year, we made a commitment to apply key learnings from the ADDRESS and ADVANCE subcu trials to all ongoing and proposed indications. The first one we focused was the pilot study of efgartigimod in bullous pemphigoid. We stopped enrollment in the Phase II and are currently waiting for data to mature across all patients. We will be ready to communicate a path forward this year, whether to change the study design and go on with Phase II, advance to Phase III or stop development in BP altogether. We also completed a thorough risk assessment of all of the programs across efgartigimod and empa, recognizing the need to be disciplined in where we invest our capital and time.

Based on our re-evaluation, we have decided to discontinue development in ANCA-associated vasculitis, or AAV, and to focus instead on a newly-nominated indication, systemic scleroderma. We determined the risks did not outweigh the benefit in AAV, given the potentially unmanageable interference of background medications. All other indications are advancing forward, with trials underway in MN, LN and AMR for efgartigimod; and DGF and DM for empasiprubart. We have plans to nominate additional indications for both assets later this year. Our opportunity to transform autoimmunity remains strong. The more data we generate in the clinic and translationally, the more informed we can get in our R&D investments and selecting indications where we can win. This is the best format for long-term value creation and is a perfect transition to Karl to talk about our financials.

[Karl Gubitz, executive]

Thank you, Tim. Slide 8. The first quarter 2024 financial results are detailed in the press release of this morning. I will highlight the key points here. Total operating income in the first quarter totaled $413 million. This reflects $398 million in product net sales and $14 million in other income and collaboration revenue, including $2 million in royalty income from Zai Lab for VYVGART sales in China. Product net sales of $398 million represents 83% growth, plus $180 million compared to the same period in 2023.

Here is a regional breakdown along with key drivers: $347 million in the U.S. with notable expansion of patients on VYVGART Hytrulo; $18 million in Japan, indicating strong volume growth, offset by a recent 8% price decrease. EMEA had an excellent quarter with net product revenues of $31 million. The majority of sales still come from Germany, where we had strong volume growth, offset by higher accruals due to the planned reassessment of the German price, which will be finalized in 1Q 2025. We saw meaningful revenue contributions this quarter from Italy and Spain, and these launches are just ramping up. We also saw our patient reach expand in Eastern European countries like Poland, and ex-EU countries like Saudi Arabia and Switzerland, through named patient sales. We expect these sales to be an important source of growth going forward as we finalize pricing and reimbursement discussions. We also had $2 million in product net sales to Zai Lab for a launch in China.

Slide 9. Operating expenses in Q1 were $506 million, a decrease of $51 million compared with Q4 2023. Excluding the $102 million impact of a priority review voucher in Q4 2023, our operating expenses increased by $51 million. The increased expenses reflect our continued conviction in the long-term opportunity we have for value creation. SG&A expenses were $236 million in Q1, which is an increase of $27 million compared to Q4 '23 due to incremental investment in the commercial infrastructure, most notably expanding our customer-facing organizations in the U.S. to capitalize on the MG opportunity and prepare for potential CIDP approval.

R&D expenses for the first quarter were $225 million. Excluding the impact of a PRV from the fourth quarter, we had an increase in the underlying spend of $21 million. This increase reflects our continued investment in our pipeline, and we currently have 48 clinical trials across 19 indications and 3 pipeline candidates. The net cash burn for the first quarter was $75 million. We continue to have a strong balance sheet with $3.1 billion in cash, cash equivalents and current financial assets. Our finance guidance for 2024 remains unchanged.

I will now turn the call over to Karen, who will provide details on the commercial front.

[Karen Massey, executive]

Thank you, Karl. Slide 10. I'm proud of the continued momentum of the VYVGART launch, expanding our impact to give more gMG patients the opportunity to return to the activities they love, and preparing to do the same for the CIDP patient community ahead of our June PDUFA date.

Before I get into details on the quarter, I want to highlight 2 things: First, we are changing the gMG treatment paradigm with VYVGART. Our ambition is to enable patients to live without the constant reminder of their disease, and we can achieve this with VYVGART in a majority of patients. We now have extensive real-world evidence and clinical trial data extending out beyond 9 treatment cycles. That data consistently show approximately 50% of patients are able to achieve MSE or minimum symptom expression. This translates into a very strong value proposition because patients report quality of life measures that are comparable to a healthy population. This is what paradigm-changing means for patients, for physicians and for the societies in which we operate.

Second, we are making decisions today that will benefit us for the CIDP launch and beyond. We are planning for the long term, sustained growth, and we want to ensure that everything we do today can be leveraged to support that growth. We believe we have the right strategy in place. And now with our expanded customer-facing team, we will be even better placed to reach new patients.

Slide 11. Our launch momentum continues with 9 consecutive quarters of revenue growth. We have year-over-year revenue growth of 83% and we see consistent growth across every region, with more than 10,000 patients on treatment globally. This is an incredible achievement and we are very happy with the momentum we continue to generate from our launch strategy. Even with this sustained growth, we are still at the beginning of what we want to achieve and we are broadening our patient impacts through our multidimensional expansion strategy.

First, we want to reach patients earlier in the treatment paradigm by innovating on the patient experience with formats like the prefilled syringe. Second, we want to expand our reach by seeking regulatory approval in new geographies. And third, we want to expand our label with new indications.

Slide 12. In the U.S., VYVGART Hytrulo was a key driver of our growth this quarter. So let's start there, because it's also an important strategy of how we will leverage momentum for the CIDP launch. As of January 1, we had payer policies and a dedicated J code in place and we saw a strong uptake of Hytrulo over the quarter, with 34% growth from Q4 in patients on our subcutaneous product. The majority of these patients are brand-new to the VYVGART franchise, which reflects the opportunity that we have to expand within our gMG addressable market with VYVGART Hytrulo.

With the backdrop of new innovations coming to market, our total market share across IV and subcutaneous increased over the quarter and we continue to expand the breadth of our prescriber base to now 2,700 neurologists using VYVGART or VYVGART Hytrulo in the U.S. The first quarter of the year is notoriously challenging and we were not immune to the impact of recertifications, holidays and weather. Taking the seasonality into consideration, I am very pleased with our performance. The underlying fundamentals of our business are strong and I have confidence that we are well positioned to maintain our growth momentum in gMG as we look ahead to the additional drivers this year.

Slide 13. The contribution from our ex-U.S. markets was another key driver in the quarter and we saw 46% quarter-over-quarter growth in patients on therapy in Europe specifically. We are encouraged to see this growth materialize. It's consistent with our expectations that Europe will represent an increasingly larger proportion of the opportunity over time. The volume growth can be attributed to meaningful uptake in Italy and Spain following pricing and reimbursement negotiations in those countries, but also the impact of the approval and launch of VYVGART subcutaneous. Whereas in the U.S., the strategy with subcutaneous is market expansion, in Europe, we see both the patient switch and the market expansion strategy. This is reflected in the growth this quarter.

Moving to Japan. It has been a very busy quarter. In addition to delivering continued growth in gMG and securing approval for VYVGART subcutaneous, we received the first global approval for our second indication, ITP. This is an important milestone for VYVGART and an important moment for ITP patients, where there is a clear unmet need in the market. This was reflected in how quickly after approval, ITP patients in Japan began treatment on VYVGART.

And finally, in China, through our partner, Zai Lab, we reached an additional 2,700 patients in the first quarter alone, driven by VYVGART's inclusion on the NRDL. Demand has been very strong. You can see that our global launch efforts are steadily progressing. We are expanding our reach into new countries and new indications and expect to further accelerate growth as more opportunities come online.

We are on track to receive VYVGART decisions on approval this year in Australia, Switzerland, Saudi Arabia and South Korea, and with VYVGART subcutaneous in China. And we have filed our CIDP regulatory submissions in Japan and China, with the EU to follow.

Slide 14. Moving to indication expansion in CIDP. We expect a decision on approval in the U.S. next month and preparations are well underway to expand our commercial engine to support this launch. CIDP patients continue to face a significant burden despite the availability of current treatment. The unmet need is high, with patients failing to see meaningful innovation in the last 30 years. Our data suggest that 88% of patients on current therapy still experience residual symptoms and patients are constantly balancing the trade-off between efficacy and the treatment burden. A couple of weeks ago, the team had the chance to hear first-hand accounts from patients suffering from CIDP.

One story really struck me, with the patient saying, "What hurts the most is not having the treatments we deserve. All I want is to get back to the things that make me feel alive." This patient is on a high dose of IVIg, which typically requires a 2-day administration period. She cannot afford to be away from work for this time, so she consolidates her treatment into 1 day, which is not sufficient to address her needs and has led to disease progression. Our goal with VYVGART Hytrulo is to provide the convenience of a 30- to 90-second injection without compromising on safety or efficacy.

And we believe this is possible from the ADHERE data, which we shared with the neurologist community at AAN. This is the largest trial in CIDP ever run, enrolling 322 patients. Data demonstrated a consistently strong response regardless of prior therapy, and we also saw data that showcased the real-world impact for CIDP patients. We successfully demonstrated efgartigimod's ability to drive a sustained improvement in functional strength across prior therapy groups, including almost 30% who improved 3 or more points on the INCAT scale. As Tim mentioned, a 3-point improvement can signify the difference from using a wheelchair to walking. This is what a transformational outcome looks like in CIDP.

Slide 15. We are well-positioned to capture the CIDP opportunity in front of us. And as I said earlier, we're making decisions today to support our future success, leveraging our learnings and capabilities from the gMG launch and applying them to CIDP. We will take a consistent approach with each of our stakeholder groups to maximize its potential: Early engagement with payers, disciplined execution to reach the right prescribers and always putting patients at the center of our innovation mission. We have already started our work on enabling broad access for patients. In MG, we partnered with payers so that they could see the value VYVGART creates for the health care system, and we will take the same approach in CIDP. We have a strong value proposition based on the ADHERE data and the open-label extension study. But it takes about 2 quarters after approval for payer policies to kick in, which will have an effect on new patient starts during 2024.

With prescribers, we have expanded our customer-facing team to maximize growth in MG while also delivering a successful launch in CIDP. CIDP is an improved indication for IVIg. So this will be a competitive market, but we are equipped to meet the challenge. And last, as we saw in MG, patients and their communities will play an incredibly important role. In our market research, we've seen that it is a big step for CIDP patients to consider switching their treatment. Our goal is to raise awareness and to empower patients so that they can become advocates for their own care. It will take some time at first, but once the community starts to experience the impact of VYVGART, I'm confident it will happen. I'll now turn the call back to Tim.

[Tim Van Hauwermeiren, executive]

Thank you, Karen. Slide 16. I'm truly proud of the argenx team. Through relentless execution, we achieved an incredible milestone of treating over 10,000 patients globally. Our commitment to innovation on all fronts has supported this phenomenal growth, from generating new data in the clinic that strengthens the use case for VYVGART, to our sales team moving deeper into the community setting to reach early line patients. We will continue to diligently invest in and execute across our business to maximize the opportunity ahead of us. It is an exciting time for the company as we actively prepare to bring a game-changing alternative to the CIDP community while staying focused on advancing our pipeline.

With novel [ finds ], we plan to uncover new opportunities to elevate treatment expectations and create value over the long run for autoimmune patients. I would now like to open the floor for questions. Thank you.

[Operator]

[Operator Instructions] Your first question comes from the line of Tazeen Ahmad from Bank of America.

[Tazeen Ahmad, analyst]

Tim, can you just give us a sense about how you're thinking about competitive landscape, because that seems to be an increasing question that we're getting? Maybe just for gMG, you have talked about increased players in this space. In the time that those have been on the market, how can you talk about the market share that you've had? Have you seen any market share loss as a result of increased competition? And where would you think most of the competition is coming from?

[Tim Van Hauwermeiren, executive]

Thank you, Tazeen. Thank you for joining us on the call today. And I think this is an excellent question for Karen to address. So I'm going to hand over to Karen straight away on the competition.

[Karen Massey, executive]

Thank you, Tim. I guess Tazeen, the first question you asked is around the competitive landscape and what we're seeing and what we expected is increased competition and increased entrants into the market. And what we're seeing in our performance is really strong underlying fundamentals despite those competitors coming to market. You asked specifically about market share. What we've been -- what we've seen quarter-over-quarter is our market share growing amongst biologics. And the majority of that growth is coming through Hytrulo and it's coming from new patients, directly coming from orals to VYVGART.

So at this point in time, we're not seeing significant impact on competition. I think because of the value proposition that we have with VYVGART and VYVGART Hytrulo, we've set the bar really high in terms of efficacy. We continue to show in the real world that our favorable safety profile plays out and of course, with both VYVGART and Hytrulo, we have that low treatment burden. So the whole package, as well as our team, is competing really well. And of course, what we see in MG across the board is that we're just at the beginning of the opportunity. And I think the more innovation that comes to market, the more the biologic share overall is going to grow and the more that we'll be able to lead within that biologic share.

[Operator]

Your next question comes from the line of Rajan Sharma from Goldman Sachs.

[Rajan Sharma, analyst]

Just on the PFS filing and maybe related to that competition question, could you just sort of walk us through the steps to approval from here? Have you had any initial interactions with the agency or shared any data? And is there anything you can say about the potential regulatory review process? Is it a faster market opportunity, for example?

[Tim Van Hauwermeiren, executive]

Yes. Thank you for the question. The PFS, of course, is a centerpiece in our strategy for VYVGART overall. Remember, we're patient-centric and ultimately, we think the prefilled syringe is going to be an important addition to the toolbox to serve patients in the most complete fashion possible. The meaningful update today, and I'm delighted to give that update actually, is that we did succeed in compiling [indiscernible] data from a bioequivalence point of view and of course, the human factors study.

Remember, these were the 2 key data sets we needed to compile in order to submit the dossier. So we're on track to submit the dossier with the FDA before the end of June, which is great. And then, of course, it's going to be in the hands of the FDA. You know the exact review time remains to be seen, but I'm confident in the quality of the data and the strength of the data, which we have submitted. So I would say stay tuned, and we will keep you informed on the progress we make with the prefilled syringe. Thanks for the question.

[Operator]

Your next question comes the line of Derek Archila from Wells Fargo.

[Derek Archila, analyst]

So this one's for Karen. You cited some market research on CIDP patients potentially switching to VYVGART. So we were wondering, I guess from that research, what percent of patients said they would actually switch? And what's the biggest reason behind the decision to switch?

[Karen Massey, executive]

Yes. Thanks for the question. And we've been learning a lot about the CIDP market as we prepare for launch. According to our market research, what we see is that about 88% of patients still experience residual symptoms despite their ongoing treatment. But as you can imagine and as I've shared previously, the patient willingness to switch off their current therapy, it's a big step for them. It's a progressive disease. It's a serious disease.

And so it takes a lot for a patient to take that step to switch to another therapy. What we're putting in place, I would say, is a comprehensive launch plan that focuses on educating the neurologists so that they understand our data, so that they see the advantage of VYVGART, as well as empowering patients so that they can advocate for themselves and for their health care and that they can really, really see the difference. What we see across the board, both with health care providers as well as with patients is that the most meaningful parts of our data set are -- I mean first of all, the fact that it is the first innovation to come to the market in many, many years. It's the biggest trial ever run in CIDP.

And what they find compelling is the broad response rate, that 70% response rate in Stage A, as well as the efficacy that's seen in Stage B, and Tim shared during the call, in particular, the improvement on function. That is really compelling. And then, of course, the package is rounded out by the safety profile and the low treatment burden. So overall, what both health care providers and patients like about VYVGART is the fact that they don't have to balance between that trade-off between efficacy and treatment burden. So we have strong conviction over the long term that we'll be able to have a lot of patients on VYVGART.

[Operator]

Your next question comes from the line of James Gordon from JPMorgan.

[James Gordon, analyst]

My question is about VYVGART and CIDP labeling. So we've seen the ADHERE data presented, but I don't think we've seen the open-label extension data yet. So is your hope or your expectation that we get that data on the label in June? And is the thinking that, that would allow for intermittent dosing as well, based on the OLE and that's how you'd address the potentially quite high price in CIDP? And also just on pricing in CIDP, am I right that if patients in MG use a lot more than the average patient, that the pricing is capped? Are there mechanisms you would potentially be able to cap the price in CIDP, because one of the questions I've had is how pricing could work in CIDP and whether that could be a barrier to use?

[Tim Van Hauwermeiren, executive]

Thank you, James, for the question. Thank you for joining us on the call today. I will hand over in a second the pricing question to Karen. From a labeling point of view, James, of course, we need to wait and see how the conversation is going to go with the FDA. I cannot put myself in their shoes, but I think it's reasonable to assume that given the randomized controlled trial was done with weekly subcu dosing, that the label would be reflecting that. The data you refer to or you allude to in the open-label extension, where we go to less frequent dosing, that could actually have a meaningful impact in our payer conversation. And that's a nice segue, Karen, into the pricing question.

[Karen Massey, executive]

Yes. Happy to address this. It's an important one. So as you said, the price was set with MG, the price per vial, but at the time with an eye towards the CIDP launch and potential CIDP launch. So the approach that we'll take setting price aside to ensuring access for patients is the same approach that we took with MG. And you mentioned during that -- part of that approach was value-based arrangements through discussions with payers.

And so we'll take a similar approach. Most importantly, when we have discussions with payers and what our commitment is in the company is that we want to create value for the health care system. I think we've demonstrated that we can do that with MG and that's reflected in the favorable payer policies we have, whether you look in the U.S., those favorable payer policies; when you look in Canada, with the recent CADTH description that we've got is dominant over IVIg; or even the progress in Europe, with the reimbursement that we're getting across the board. You can see that VYVGART is creating value for health care systems and our approach is creating value. And so we'll take the same approach with CIDP to make sure that we get broad access for patients and I'd say in terms of preparations for the launch, our discussions are on track and our commitment to broad access to CIDP patients remains the same.

[Operator]

Your next question comes from the line of Akash Tewari from Jefferies.

[Akash Tewari, analyst]

So looking at the geographic breakdown, it looks like U.S. VYVGART patient adds are starting to sequentially flatten out. That said, you mentioned 50% of your new patient adds are now from patients getting off of orals. As we think about 2025 and beyond, do you think that MG will remain a growth market for VYVGART? And have you seen any signs of uptake in the 70,000 patients upstream to the 17,000 that are currently not well-controlled by steroids?

[Karen Massey, executive]

Yes, thanks for the question. And I would say, actually, I'm very confident that we're just at the beginning of the growth curve with MG. We actually see quite consistent new patient starts that are coming on board. As you said, they're generally coming from the orals, over 50% of those are coming from -- directly from the orals. And as part of that, we're advancing our market share amongst biologics. In particular, Hytrulo is really helping us to advance into those earlier lines of treatment and to expand the breadth of our prescriber base.

So we have about 2,700 prescribers now. The majority of that 34% growth in new patients for Hytrulo, they're naive to VYVGART. So those are new patients. So the way I see it, we're at the beginning of the curve. Overall, the biologics in MG are a small percentage of the market. We're leading, that biologic share is growing and we have a long way to go ahead of us in VYVGART, and a lot of opportunity.

[Tim Van Hauwermeiren, executive]

And in addition, Akash, to what Karen just said, we also announced the start of the acetyl-negative MG trial, which is going to be a label-expanding trial, right? About 15% of MG patients are estimated to be acetyl-negative. So that will also be a meaningful addition to the label in case this trial is successful.

[Operator]

Your next question comes from the line of Yaron Werber from TD Cowen.

[Yaron Werber, analyst]

Great. So maybe one that's related to the pipeline. I think in the past, you've talked about potentially doing an R&D Day, kind of at some point this year, maybe in the summer or in the fall. What would you want to cover if you were to do such an R&D Day? And then secondly, the decision to move to systemic scleroderma, it sounds like with [indiscernible] scleritis, there's too much variability in background meds, what do we know about scleroderma? How homogeneous is it? What percentage of patients are autoantibody positive, if you can give us any sense?

[Tim Van Hauwermeiren, executive]

Thank you for these questions, Yaron. Thank you for joining us. So look, there's a ton in this company to talk about when you organize an R&D Day. So we will have to make choices and we're carefully listening to the customer of such an R&D Day. For sure, a centerpiece will be the full data presentation on MMN, which is the lead indication for empa. But we also received strong feedback about the continuous need to be educated on some of these newer indications, which we started to talk about. So stay tuned. I think that will be communicating in the not-too-distant future about the date and the agenda of the R&D Day.

On systemic scleroderma, this is an indication which was always high on the list. You remember that we always start from a very strong biology rationale. So talking about a strong biology rationale in systemic scleroderma, we have a very good understanding of the autoantibodies of the IgG type. These autoantibodies actually work very well in passive transfer models, where antibodies from patients transferred into animal models actually caused the phenotype of the disease. We also know a number of the autoantigens. So if you immunize these animals with the autoantigens, again, they develop the typical symptoms of the disease. And then, of course, plasma exchange works, IVIg works, rituximab is approved in Japan. So there's a very solid body of evidence. This is an IgG-driven disease. There are useful clinical endpoints with no real approved medication outside of rituximab in Japan. So we will have to interact, of course, with the regulators and calibrate expectations on endpoints but in terms of biology rationale, unmet medical needs and feasibility of doing the clinical trials, this was an indication which made it higher on the list. And of course, we double-clicked on it, just like we did on our other indications, in the portfolio review to really understand the potential impact of background medication on autoantibody levels, taking the learnings into account of the pemphigus trial. Thanks for the questions.

[Operator]

Your next question comes from the line of Thomas Smith from Leerink Partners.

[Brian Conley, analyst]

This is Brian Conley on for Tom Smith. A couple of questions on the TED program. So with respect to your 2 Phase III studies, can you talk about how you see efgartigimod fitting into the competitive landscape there? Any specific differentiating aspects you would highlight from the way you designed your Phase III [ active ] TED studies, compared just to competitors? And are you contemplating pursuing broader development in chronic TED?

[Tim Van Hauwermeiren, executive]

Yes. So as we announced, the Phase III study campaign is open. We are enrolling whilst we speak. This will be a global trial also involving our partner Zai Lab in China. It's a sizable market opportunity. And I think in the current treatment paradigm, it is becoming clear what the shortcomings are of the currently available medications. It's a relatively similar patient population, which we're enrolling in our studies as compared to the Tepezza studies, of course, now also involving a capped number of patients, which can't have seen Tepezza in their lives. That's where we're going to stick with the update today on TED and I think we will be ready to talk more about it when we're deeper into these studies. But the big news today is study is live and is also using, by the way, the PFS.

[Operator]

Your next question comes from the line of Alex Thompson from Stifel.

[Alexander Thompson, analyst]

I guess I wanted to ask about self-administration and for CIDP, the expectation for potential self-administration at launch or whether the PFS is really the route to achieving self-administration on the label for both CIDP and MG.

[Karen Massey, executive]

Yes. Thanks for the question. We see self-administration as a really important step forward overall as we continue with our expansion strategy for VYVGART and VYVGART Hytrulo. So the label for -- if approved in CIDP will be for the current Hytrulo label. So that would be HCP administration. But as we shared earlier in the call, we're excited about the progress we're making with the prefilled syringe and the path there, according to the plan that we've laid out, is that we will have discussions around self administration and we think that there's a good, a positive path forward there for both MG and CIDP. But of course, it's always up to the FDA and a review issue.

[Operator]

Your next question comes from the line of Xian Deng from UBS.

[Xian Deng, analyst]

It's Xian from UBS. Just a general question. A general question on Sjogren's, please. So Sjogren's has traditionally been a challenging disease for normal biologics. So just wondering what gives you the confidence in VYVGART in Phase III? Do you think it's a mechanism at CRIs, a target, or some biomarker data you have collected or it's a primary endpoint? We know you already use a composite endpoint, which is arguably more comprehensive than some others. But on the other hand, in Sjogren's, you're probably also going to have quite some patients with a lot of prior medications. So just wondering, any thoughts on that, that would be great.

[Tim Van Hauwermeiren, executive]

Thanks for the questions, Xian. So the Phase II signal-finding study served 2 big purposes. Purpose one was to establish confidence in the disease biology and our understanding of the biology. Objective two was to really learn about dos and don'ts for the Phase III clinical trial design. So let's start with objective number one. I think we see a very convincing biological signal that by blocking FcRn, you're effectively eliminating the circulating immune complexes, which we think are the trigger of the disease. And by clearing these circulating immune complexes, you basically see a downstream effect in how the immune cell infiltration is going down in the glands and how systemic signs are actually improving and improving across multiple clinical scales and in hand, so consistently.

Now that's exactly what we wanted to see in addition to a positive Phase II trial, as announced for nipocalimab by our colleagues from J&J. Secondly, we learned a great deal about potential impact of background medication and how to mitigate that, the imperfections of the currently used endpoints. So I think all in all, we have conviction in the data sets and we are actually equipped to now go into our end of Phase II meeting with the FDA to discuss our proposal for Phase III. Thanks for the question.

[Operator]

Your next question comes from the line of Vikram Purohit from Morgan Stanley.

[Vikram Purohit, analyst]

So we just had 2 on the pipeline. First on empasiprubart for MMN. Was just curious if you could talk a bit about what that Phase III study could look like? And just kind of how you're characterizing that commercial opportunity? And then for pipeline readouts for this year, how are you thinking about the potential outcomes for the ALPHA and ALKIVIA data sets? And what would constitute strong outcomes there from your perspective?

[Tim Van Hauwermeiren, executive]

I think MMN is a sizable opportunity. Of course, it's a rare disease. It is a disease which is, I think, underdiagnosed and undertreated. As we know, the only available therapy out there is IVIg. And similar to markets like, for example, MG, I would not be surprised to see this market grow substantially with real innovation coming in. I think from a trial design point of view, we are very well-equipped to get ready for Phase III, because the main objective of the Phase II clinical trial, of course, next to establishing proof of concept, was to establish a dose response range where we can basically populate our PK/PD model and predict the Phase III dose and dosing regimen.

I think we're very close to that point. We also had a very rich trial here in terms of clinical endpoints. And we already said that all clinical endpoints really moved in sync with each other. So we will be able to have a real educated discussion with the FDA about which endpoint we would suggest and why we would be suggesting that endpoint out of the many ones which we tested. So I think we will be in a strong position to engage in that end of Phase II discussion with the FDA relatively soon.

In terms of other outcomes this year, we are, of course, waiting now after the positive Phase II data for Sjogren's, we're waiting for the PC-POTS data, which should come in before the middle of the year. And then, of course, the 3 myositis trials, which will come in during the second half of the year.

Similar to Sjogren's, in PC-POTS, we will be really looking for proof of biology. Whilst you should be thinking of the go/no-go decision point in the myositis studies in a similar fashion as we designed them for the CIDP study. So we will want to see a signal which is reasonably to be expected, stronger than what the placebo signal could be in order to advance in 1, 2 or 3 of these subsets of myositis, and we will be communicating about these go/no-gos at the same time for all 3 indications. Thanks for the questions.

[Operator]

Your next question comes from the line of Danielle Brill from Raymond James.

[Danielle Brill, analyst]

I want to circle back to the CIDP launch. Based on recent doc checks, it seems like many patients may have already been earmarked for therapy with VYVGART. I'm wondering what, Beth, you're encountering in your market research and is there any reason at this point to think that the launch cadence won't be similar to what we saw in MG?

[Karen Massey, executive]

Thanks for the question, Danielle. And we're seeing something similar in market research in one way is -- in that there is excitement amongst prescribers and patients about VYVGART and the potential. We are not seeing that there's a bolus of patients that are waiting. And in particular, the prescribers have the same question that many of us have, which is when will the payer policies come online. And we know that payer policies generally take a couple of quarters to come online after an approval.

So I think the uptake, combined with the payer policies coming online, that patient stickiness to IVIg that I talked about a little bit earlier, as well as the fact that IVIg is approved in this indication and will be a strong competitor, I think that means that we can expect to see maybe a little bit of a slower uptake versus MG. However, once we start to get the patient switches happening and once we start to shift the market, then I think that -- I'm confident that over the long term, this is a big opportunity, even if it won't be easy in the first phase. Thanks for the question.

[Operator]

Your next question comes from the line of Suzanne van Voorthuizen from Van Lanschot Kempen.

[Unknown Analyst]

It's [ Cara Montiania ], I'm on, on behalf of Suzanne. So out of curiosity, again, on the drop of the ANCA program, which was replaced by SSc, I was wondering how does 2 indications compare in terms of efforts, trial design, time lines or anything that you wish to highlight?

[Tim Van Hauwermeiren, executive]

Roughly speaking, I would park them in the same ballpark in terms of size of opportunity and size of investment. And the unmet medical need in AAV is substantial. The biology, by the way, is very strong. Actually, the disease is called after these autoantibodies. And we saw a recent case report published with spectacular data for VYVGART in the hands of physicians in the real world.

The real issue for AAV, I think, is the confounding factor of the background medication, the mandated use of high dose of steroids is actually going to blur the effect of VYVGART. And we looked at it from multiple angles, but there is no credible way to go through that steroid barrier despite a high unmet medical need. That is quite different in systemic scleroderma. So equally high unmet medical need, equal number of patients, equally strong biologic rationale, but I think a more straightforward path in clinical development. That's how I would call it for the time being.

[Operator]

Your next question comes from the line of Samantha Semenkow from Citi.

[Samantha Semenkow, analyst]

My question is just on the uptake of Hytrulo. Is the growth that you highlighted in the prepared remarks, is that a recent uptake? Or has it been steadily climbing over the last several quarters? And then as you think about introducing PFS as an approved option, formulation, would you expect a similar trajectory of growth for the PFS? Or would you expect it to be a sharper uptake?

[Karen Massey, executive]

Yes. Thanks for the question, Samantha. I'll take that. We actually did see an acceleration in the uptake of Hytrulo in Q1 and there were specific reasons for that, namely that the payer policies were in place and the J code was established in Q1. So we did see an acceleration. We expect that to continue. And it's important to note, just in -- we were just talking about it in the CIDP launch, it did take about 2 quarters for those payer policies to come into place with Hytrulo, so we've seen that now. In moving forward, I think we're very excited about the prefilled syringe and being able to offer an even broader product presentation option to patients. I do think it's a significant advancement on the current Gen 1 of Hytrulo and I do think it will enable us to further move up to earlier lines of treatment with VYVGART and further advance or expand our prescriber base as well. So we do see that, that PFS will be another engine for growth, if you will, for VYVGART. Thanks for the question.

[Operator]

Your next question comes from the line of Gavin Clark-Gartner from Evercore ISI.

[Gavin Clark-Gartner, analyst]

On empa in the pipeline, I believe you've noted there's been no cases of lupus in the ongoing MMN study. But I also wanted to ask about rates of ANA titer elevations, specifically any other markers such as dsDNA.

[Tim Van Hauwermeiren, executive]

Yes, that's a great question. And a potential difference here actually for C2 versus the C1, no, we did not see any increase of such titers. And at least from a theoretical point of view, we have always believed this could be one of the advantages of an anti-C2 antibody. So none of these signs and a great opportunity for me to remind everyone on the call that the Phase I data, both for IV and subcu, came out with spick-and-span safety and tolerability data. So, so far, so good. Thanks for the question.

[Operator]

Your next question comes from the line of Yatin Suneja from Guggenheim.

[Yatin Suneja, analyst]

Quick one for me. On VYVGART, could you comment on what you're seeing in terms of discontinuation there? Is it in that 20% range? And then anything you are able to say on number of cycles that you are able -- that patients are getting?

[Karl Gubitz, executive]

Thank you for the question. On discontinuation, as you know, 20% of the patients from the ADAPT study did not respond. So you would expect the discontinuation to be 20% plus because there are also other reasons. And what we see in the real world is in line with our expectations. That has been consistent since launch. In terms of the number of cycles, the number of cycles for IV has also been consistent and we're about -- and it's around 5 as we previously said. So there will be no change.

[Operator]

Your next question comes from the line of Victor Floch from BNP Paribas.

[Victor Floch, analyst]

So a couple of questions on my side. First, I was wondering if it's fair to say that the SG&A cost savings we've seen this quarter is replacing a higher need to build up awareness ahead of launch in CIDP than what was needed for MG back in the day. So if you could just remind us the key challenges in CIDP compared to MG, would be appreciated. And my second question is about ITP. And so I was just wondering if you could update us on your efforts to potentially extend the ITP opportunity beyond Japan. So I don't know what is in the balance to take any decision. And if you could commit to any timing. But any color on that would be very much appreciated.

[Tim Van Hauwermeiren, executive]

Thank you for the question. I will give the floor in a minute to Karl, who is going to comment on the increase in SG&A expenses in preparation of the CIDP launch. Karl, you will be able to give some color there.

Thank you for your question on ITP. We are, of course, delighted to see the PMDA approval for ITP. We see the first patients coming on product very quickly, underscoring, I think, the unmet medical need which is present in ITP. And I think it's fair to say that throughout the interactions with the PMDA, we also gained a number of insights we can use to actually pivot back to the FDA for a follow-up conversation. And that's exactly what the team is preparing. I think we're equipped now to go back to the FDA for a dialogue to see whether we can make progress on the ITP front. So stay tuned. I certainly don't want to overpromise, but I think we're going to make an extra effort there, which I think we owe to ITP patients. Karl, would you mind commenting on the SG&A step-up?

[Karl Gubitz, executive]

Okay. SG&A increased by around $27 million in Q1 '24 versus the end of last quarter in '23. That increase is largely driven by the incremental infrastructure we put in place in the U.S. This is customer-facing colleagues which will be promoting gMG today. And as we said previously, we believe that the gMG opportunity is bigger than what we originally thought and now we're expanding that footprint. That same footprint will also be used for the CIDP launch subject to approval later this year. Also part of that increase is the geographical expansion. You've heard us talk about certain markets like Italy and Spain and other European markets where we're starting to have sales. We've been very disciplined to gate any expenses in those markets until we have pricing and reimbursement in place. And as we start seeing sales in those markets, we are investing in those markets. So it is the U.S. and the geographical expansion which is driving that increase. Thank you for the question.

[Operator]

Your next question comes from the line of Joel Beatty from Baird.

[Joel Beatty, analyst]

With Q1 typically being a challenging quarter, how did the trajectory of VYVGART sales change over the course of the quarter into early Q2?

[Karen Massey, executive]

Yes. Thanks for the question. As you said, Q1 is notoriously challenging in particular in the U.S., with holidays and recertifications and weather, et cetera. We're really pleased with the growth, the quarter-on-quarter growth that we delivered in the U.S. as well as the year-on-year growth. I mean it was 76% year-on-year growth for the U.S. What we're seeing and what we feel is confidence that the underlying fundamentals of what we delivered in Q1 were very strong. And I went over a few of those, whether you look at new patient growth, where the patients are coming from, we're advancing market share, all of those factors and we're seeing that continue into Q2. So we're confident in the remainder of the year.

[Operator]

Your next question comes from the line of Manos Mastorakis from Deutsche Bank.

[Manos Mastorakis, analyst]

Just basically on the key learnings you took away from the exercise you did across indications and which led to the discontinuation of ANCA vasculitis and how do some of those learnings extend to empasiprubart?

[Tim Van Hauwermeiren, executive]

Thank you. It's a great question. Actually, when we did the portfolio review, we did not only limit it to efgartigimod, we immediately included also the empa indications. So we did a full review of all plans and ongoing indications. And we gained confidence for all empa indications, which are currently on the rails, but also the ones which we're planning in addition that actually we can master the impact of the background medication.

So I feel very strong about the big efforts all the teams did in such a short period of time following the pemphigus data. We thoroughly double-clicked on trial designs, understanding the impact of background medication and whether or not we're actually equipped to deal with those. So exercise has landed. And actually, most indications remain on track with the exception of AAV, where we no longer feel it's a responsible allocation of capital, to take such a risk from a background medication point of view. Thanks for the question.

[Operator]

Your next question comes from the line of Matt Phipps from William Blair.

[Matthew Phipps, analyst]

Two quick ones. First, on the human factors studies, did you use CIDP patients in that study? I'm just wondering if somebody with reduced grip strength would be suitable for self-administrated PFS? And then I guess following the potential CIDP approval, given what you said about the payer policies, would you plan to provide some kind of free drug program given the underlying patient interest and demand?

[Tim Van Hauwermeiren, executive]

Thank you for the 2 questions. I will hand over the second question in terms of launch preparation to Karen, although I suspect we will not be showing too much of our cards. From a human factors study point of view, you're absolutely right. I mean we're targeting the prefilled syringe for both gMG and CIDP patients. So you can imagine that in the human factors studies, both patient groups were actively involved. And we feel very strong about the data which we achieved and we feel very strong about the submission, which is now in the works before end of June. Karen, question two, please.

[Karen Massey, executive]

Yes, happy to. Without going into too many details exactly on what our plans are, maybe the best way to answer that is we're taking the same approach to the CIDP launch preparation as we did with MG. And the way that I would characterize that is that we're being really -- thinking very innovatively about how we want to go to market, how we want to empower patients, how we want to educate prescribers. And we're also thinking in a very disciplined way around our execution and how do we make sure that we're making the right capital investments or the right use of our capital and making the right investments. So we'll take that same approach for the CIDP launch that we did for MG.

[Operator]

And your final question comes from the line of Douglas Tsao from H.C. Wainwright.

[Douglas Tsao, analyst]

Just a quick one for me. I'm just curious, ultimately, when we think about the different presentations of efgartigimod, I mean where do you see the prefilled syringe ultimately falling between the subcu and the IV? I mean do you think that this could ultimately become the sort of dominant presentation that's utilized?

[Tim Van Hauwermeiren, executive]

Yes. Thank you for the question. So we are a patient-centric company and it's our ambition to serve the needs of the individual patient segments as completely as we can. We believe that especially in the U.S. market, the IV product will always be important because a subset of patients, but also actually physicians, do prefer an IV infusion.

The interesting thing about VYVGART Hytrulo today is that it's actually a very clean and easy execution, which is still resorting under mainly at, I would say, Medicare Part B, whilst the PFS with the self-administration is mainly going to target, I think, or sit in the Medicare Part D channel. So if you think about the market leader who is patient-centric, I think the PFS will be the closing piece in the totality of the product offering, maximally serving, I think, different needs and preferences of different market segments. Thanks for the question.

[Operator]

And we have now reached the end of our question-and-answer period. This concludes today's conference call. Thank you for your participation. You may now disconnect.