Earnings call: Alnylam reports strong growth and pipeline progress
Alnylam Pharmaceuticals (NASDAQ: ALNY) has reported a significant year-over-year increase in global net product revenue for Q3 2024, with a total of $420 million representing a 34% growth. The TTR franchise, which includes treatments such as ONPATTRO and AMVUTTRA, was a major contributor to this success, generating $309 million. The company also provided updates on its promising pipeline, including advancements in treatments for Alzheimer's disease and Huntington's disease, and reaffirmed its revenue guidance for 2024.
Key Takeaways
Alnylam Pharmaceuticals reported a 34% year-over-year increase in global net product revenue, reaching $420 million.The TTR franchise led the revenue growth with $309 million, a 34% increase, serving nearly 5,000 patients globally.Promising results from the HELIOS-B study of vutrisiran and progress in studies for Alzheimer's and Huntington's diseases were highlighted.The company is advancing its clinical development pipeline and aims to double it by the end of 2025.Alnylam reiterated its guidance for combined net product revenues between $1.575 billion and $1.65 billion for 2024.Company Outlook
Alnylam is preparing for the U.S. and EU launch of AMVUTTRA in 2025, with increased commercial investments anticipated.The company remains committed to achieving its Alnylam P5x25 strategic goals and doubling its clinical pipeline.Management is exploring business development opportunities to further enhance growth.Bearish Highlights
Collaboration revenues decreased to $57 million due to the absence of prior upfront payments.Bullish Highlights
Royalty revenues increased to $23 million, and the gross margin on product sales improved to 80%.The TTR market continues to grow, with Alnylam's products showing strong demand and competitive advantages.Misses
Alnylam has ceased the ALN-KHK program for type 2 diabetes to reallocate resources more effectively.Q&A Highlights
The company is open to business development opportunities that enhance their platform.Further clarification on the timeline for a second indication launch for their product is needed closer to the launch date.
Alnylam Pharmaceuticals has demonstrated solid financial performance and pipeline progress in the third quarter of 2024. With the TTR franchise as a key revenue driver and promising clinical results in its rare disease portfolio, the company is well-positioned for future growth and innovation in the biopharmaceutical industry.InvestingPro Insights
Alnylam Pharmaceuticals' impressive Q3 2024 performance is reflected in its robust financial metrics and market position. According to InvestingPro data, the company's revenue growth has been exceptional, with a 107% increase in quarterly revenue as of Q2 2024. This aligns well with the reported 34% year-over-year increase in global net product revenue for Q3 2024.
The company's gross profit margin stands at an impressive 87% for the last twelve months as of Q2 2024, underscoring its efficiency in production and pricing power. This high margin supports Alnylam's ability to invest in its promising pipeline and advance treatments for rare diseases.
InvestingPro Tips highlight that Alnylam has shown a strong return over the last three months, which is consistent with the positive outlook presented in the earnings report. The company's liquid assets exceeding short-term obligations suggest a solid financial position to support its growth initiatives and pipeline development.
It's worth noting that while Alnylam has demonstrated impressive revenue growth, an InvestingPro Tip indicates that analysts do not anticipate the company to be profitable this year. This aligns with the company's focus on long-term growth and investment in its clinical pipeline, as outlined in their Alnylam P5x25 strategic goals.
For investors seeking a more comprehensive analysis, InvestingPro offers 7 additional tips that could provide deeper insights into Alnylam's financial health and market position.
Full transcript - Alnylam Pharmaceuticals Inc (ALNY) Q3 2024:
Operator: Good day, everyone, and welcome to today's Alnylam Pharmaceuticals Q3 2024 Earnings Conference Call. At this time, all participants are in a listen-only-mode. Later, you will have the opportunity to ask questions during the question-and-answer session. [Operator Instructions] Please note this call is being recorded, and I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to the company.
Christine Lindenboom: Good morning. I'm Christine Lindenboom, Chief Corporate Communications Officer at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Medical Officer; and Jeff Poulton, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined in Slide 2, Yvonne will offer introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress, and Jeff will review financials and guidance, followed by a summary of upcoming milestones before we open the call for your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I would like to turn the call over to Yvonne. Yvonne?
Yvonne Greenstreet: Thanks, Christine, and thank you, everyone, for joining the call today. The third quarter of 2024 marked a period of continued progress for Alnylam on all fronts. Commercially, we achieved 34% year-over-year growth in global net product revenue, generating $420 million across our four marketed products. We made great progress with our TTR franchise, sharing additional results from the HELIOS-B study of vutrisiran and filing regulatory submissions in the U.S. and EU. We also hosted a TTR Investor Day to highlight our preparations in anticipation of a potential launch in ATTR cardiomyopathy next year. We believe that AMVUTTRA and our broader TTR portfolio will serve as our flagship franchise, similar and potential impact to what EYLEA has been for Regeneron (NASDAQ:REGN ) or what the cystic fibrosis franchise has been for Vertex (NASDAQ:VRTX ) delivering to those companies durable growth and enabling those companies to invest in R&D, new product development and portfolio diversification for the long term. Lastly, our early pipeline saw continued momentum as well, particularly our efforts in CNS. We initiated a Phase 1 study of ALN-HTT02 in Huntington's disease, and we're pleased to announce today initial results from the multi-dose portion of the Phase 1 study of mivelsiran in patients with early onset Alzheimer's disease. These results are encouraging for our CNS platform as they provide early evidence that multiple doses of an intrathecally administered siRNA are well tolerated. We're continuing to progress towards achievement by year-end 2025 of our Alnylam P5x25 goals and are steadfast in our belief that we're on track to become a top-tier biotech developing and ctransformative medicines for patients around the world with rare and prevalent diseases driven by a high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine, all while delivering strong financial results. With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?
Tolga Tanguler: Thanks, Yvonne, and good morning, everyone. Q3 was another strong quarter for our commercial portfolio with our combined commercial portfolio delivering year-over-year growth of 34% compared with the third quarter of 2023 as we continue to consistently increase the number of patients on therapy in both our TTR and rare franchises. Let me now turn to a summary of our third quarter TTR performance. Our TTR franchise achieved $309 million in global net product revenues, representing a 34% increase compared with the third quarter of 2023 as we continue to increase the number of hATTR polyneuropathy patients on our therapies, particularly noteworthy in the U.S. given the competitive environment. We are approaching 5,000 patients on treatment with ONPATTRO or AMVUTTRA globally, and there is still a significant growth opportunity given that our belief that 25,000 to 30,000 patients across the globe suffer from this devastating disease. Now let me provide highlights of our U.S. and Rest of World TTR performance. In the U.S., combined sales of ONPATTRO and AMVUTTRA increased by 8% compared with the second quarter and a robust 37% year-over-year as momentum in new patient adds continues to drive strong growth. The U.S. 37% year-over-year growth was primarily driven by the following, a 31% increase in demand driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO who have switched to AMVUTTRA. We are pleased with the growth in demand, which has been consistent throughout the year despite new competition entering the market at the end of 2023. Favorability is also driven by gross to net adjustment. Now let me turn to our international market, where the TTR franchise growth decreased by minus 9% compared to the second quarter of 2024, yet our quarter-over-quarter patient demand remains strong with plus 6% growth. The 9% quarter-on-quarter decrease was driven by a gross to net adjustment in Portugal that was booked in Q3 and large orders of ONPATTRO in our partner markets in Q2, including Australia, where we built inventory as we launched ONPATTRO in this market. On a year-over-year basis, the TTR business in international markets grew by 31% compared with the third quarter of 2023. At our recent TTR Investor Day, we shared our plans for the promising potential of vutrisiran in addressing ATTR cardiomyopathy pending regulatory approval. We're confident in our journey towards leadership in this field, driven by several key factors. ATTR cardiomyopathy is a rare and progressive disease where there is significant unmet need and substantial number of patients remain undiagnosed or not optimally treated. With HELIOS-B, we've shown very compelling results across key endpoints in a population reflective of today's patients. We have a track record of success in polyneuropathy and experience operating in a competitive environment. And our dedicated focus on ATTR will be instrumental as we scale for a successful launch, building Alnylam's flagship franchise and ushering a new phase of growth. Now moving to our rare franchise and the performance of GIVLAARI and OXLUMO, which delivered $111 million in combined net product sales during the third quarter, representing an 8% increase compared with the second quarter of 2024 and 34% growth compared with the third quarter of 2023. For GIVLAARI, Q3 product sales increased by 14% versus Q2, primarily due to the timing of orders in partner markets and a robust 31% compared with the third quarter of 2023 with the following year-over-year regional highlights. a 9% increase in the U.S., primarily driven by growth in new patients on therapy, a 79% increase in our rest of world markets, primarily driven by the timing of orders in our partner markets, primarily Brazil and increased demand growth across European markets. For OXLUMO, Q3 product sales were relatively flat versus Q2 2024, while delivering robust 40% year-over-year growth compared to Q3 2023 with the following regional dynamics, a 54% increase in the U.S., primarily driven by strong patient demand growth, a 33% growth from our rest of world markets, primarily driven by strong patient demand growth across both EU and our partner markets. In conclusion, our third quarter results reflect consistent strength with both our TTR and rare franchises achieving impressive patient and revenue growth. This performance positions us well to meet the midpoint of our full year revenue guidance, which we updated and raised during our second quarter earnings call. We remain intensely focused on preparing for a potential ATTR cardiomyopathy launch next year. And with that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?
Pushkal Garg: Thanks, Tolga, and good morning, everyone. As you all know, Q3 was very exciting for our TTR franchise. We shared the full results from the pivotal HELIOS-B study at ESC in August and additional exploratory findings at HFSA in September. Together, these data presentations highlighted vutrisiran's potentially transformational profile in today's population of patients with ATTR cardiomyopathy with benefits across a comprehensive series of assessments. This started with rapid knockdown of TTR, characteristic of the RNAi mechanism of action. We then saw favorable impact on cardiac biomarkers as well as echocardiographic assessments, reflecting impact on the underlying pathophysiology of this disease. This was then followed by impact on a number of important clinical measures of function and health status, indicating delays in disease progression. And ultimately, we saw profound benefits on outcomes with a greater than 30% reduction in all-cause mortality. Based on these compelling data, we've now completed regulatory submissions in the United States, where we've used a priority review voucher and in the EU with additional global regulatory submissions to follow in late 2024. Turning now to another important program for Alnylam. We're excited today to share new results from the multiple dose portion of the Phase 1 study of mivelsiran in patients with early onset Alzheimer's disease. As you recall, mivelsiran is a leading program in our effort to expand our RNAi platform to target organ systems beyond the liver and address the high unmet need that exists for neurologic diseases. Mivelsiran is a C16 conjugated RNAi therapeutic targeting amyloid beta precursor protein or APP, and is in development for the treatment of Alzheimer's disease and cerebral amyloid angiopathy or CAA. APP is the upstream precursor of all amyloid beta peptides that form the amyloid deposits that are characteristic of these two diseases. We believe that by lowering APP production, we can reduce the substrate for new amyloid deposition, potentially enable natural clearance and slow, halt or even improve the clinical manifestations of these devastating diseases. Today, we are sharing initial interim data from the first multiple dose cohort from the Phase 1 study of mivelsiran in early onset Alzheimer's disease patients. In the chart here in the dotted line, you can see the rapid, robust and sustained target engagement we achieved with a single 50-milligram dose during the single-dose part of the study as measured by the target engagement biomarker soluble APP beta. After a single dose on day zero, mean reductions of approximately 75% in soluble APP beta were seen at month 1 with sustained reduction of approximately 50% still apparent at month 6 and a slow return towards baseline thereafter. In pink, you can see the initial interim data from the multiple dose portion of the study where patients were administered 50 milligrams at month zero and 6 and then followed through month 7 or 30 days after that second dose. You can see that APP beta follows a very similar trajectory to the patients after the single dose of 50 milligrams through the first 6 months. But then after the second 50-milligram dose at month 6, we see further reductions of APP beta at month 7, with patients achieving above 90% lowering of APP beta. So these are very encouraging data as they indicate we can achieve sustained robust lowering of APP with relatively low doses. Importantly, mivelsiran has been generally well tolerated in both the single and multiple dose parts of the study. No new safety signals have been identified in Phase 1 and no significant abnormalities have been seen on CSF safety labs such as total protein and CSF white cell count or on the exploratory biomarker neurofilament light chain. Given these encouraging results, we continue to aggressively advance this program through clinical development. Specifically, we have continued dose escalation in the single ascending dose portion of the study to fully explore the safety and pharmacology profile of mivelsiran. We've now also initiated multiple ascending dose cohort in the study to explore additional dose regimens. As we announced earlier this year, we've begun a Phase 2 study in CAA, the second leading cause of hemorrhagic stroke and for which there is no existing disease-modifying treatment. And in parallel, we're defining next steps for a Phase 2 study in Alzheimer's disease and we'll provide updates in due course. Moving to another exciting pipeline update. We moved our third CNS program into the clinic with initiation of a Phase 1 study of ALN-HTT02, which targets the disease-causing Huntington protein in patients with Huntington's disease. In Q3, we shared nonclinical data supporting the broad CNS distribution as well as the tolerability of deep and sustained lowering of HTT in nonhuman primates after single and repeated intrathecal administration of ALN-HTT02. We look forward to sharing updates on this exciting program in the future as we seek to address this progressive and fatal neurodegenerative disease. As we've discussed, our potential upcoming launch in ATTR cardiomyopathy, assuming regulatory approval and near-term achievement of sustainable profitability are going to give us a strong foundation to continue investing in the promise of RNAi therapeutics to treat a broad variety of diseases with critical unmet needs. But as we've also discussed, we continue to be disciplined about resource allocation in this key phase of growth. As part of that ongoing commitment to optimize our efforts, we've announced today a decision to stop clinical development of ALN-KHK, an investigational RNAi therapeutic targeting ketohexokinase for the treatment of type 2 diabetes mellitus. This decision furthers our efforts to allocate clinical, managerial and financial resources carefully to bring transformative medicines to patients, including our other programs in the metabolic space, which is an exciting one for RNAi therapeutics. We continue to explore multiple targets for metabolic disorders and look forward to sharing updates in the future. So in sum, we've made great progress in advancing our pipeline and platform with much more to come. As a reminder, we're working towards filing proprietary INDs for 9 programs by the end of 2025 against targets in the liver, CNS, muscle and adipose. If we include partnered programs, we anticipate the potential for 15 new INDs by the end of 2025, representing a near doubling of our clinical pipeline by the end of next year. This remarkable and unique pace of innovation puts us in a great position to have a robust, self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?
Jeff Poulton: Thanks, Pushkal, and good morning, everyone. I'm pleased to be presenting a summary of Alnylam's Q3 2024 financial results and discussing our full year guidance. Starting with a summary of our P&L results for Q3 2024 compared with the same period in 2023. Total product revenue for the quarter was $420 million or 34% growth versus 2023, with both our TTR and rare franchises reporting strong growth of 34%, primarily driven by continued strong demand, as Tolga previously highlighted. Net revenue from collaborations for the quarter was $57 million, representing a $370 million decrease when compared with last year. The decrease was primarily driven by the recognition in Q3 2023 of the $310 million upfront payment from Roche as well as the $65 million in revenue recognized from a $100 million milestone earned for achieving certain criteria during early clinical development for mivelsiran. Royalty revenue for the quarter was $23 million or more than double what was recognized in the third quarter of 2023. The increase was driven by higher Leqvio sales as Novartis (SIX:NOVN ) continues to grow demand for Leqvio worldwide. Gross margin on product sales was 80% for the quarter compared with 75% in the third quarter of 2023. The improvement in margin is primarily due to higher costs in 2023 associated with canceled manufacturing commitments for ONPATTRO and other adjustments to inventory, for which similar expenses did not occur this year, offset by an increased rate of royalties payable on net sales of AMVUTTRA. I expect our gross margin on product sales will be lower in Q4, driven by a higher royalty rate payable on sales of AMVUTTRA. Our non-GAAP R&D expenses increased 12% in the third quarter compared to the same period last year, primarily due to increased costs associated with our preclinical activities as we progress our 225 strategy to expand our clinical pipeline by the end of 2025 as well as clinical activities, which mainly grew with expenses associated with zilebesiran KARDIA-3 Phase 2 clinical study and increased personnel costs. Our non-GAAP SG&A expenses increased 19% in the third quarter compared to the same period in 2023, primarily due to higher costs associated with marketing investments to promote our TTR therapies and preparations for the potential launch of AMVUTTRA for cardiomyopathy, along with increased personnel costs. Our non-GAAP operating loss for the quarter was $31 million, representing more than a $300 million decrease compared with Q3 2023, primarily driven by the recognition of collaboration revenue related to our Roche agreement and achievement of a mivelsiran milestone last year, as previously highlighted. We ended the quarter with cash, cash equivalents and marketable securities of $2.8 billion compared with $2.4 billion as of December 31, 2023, with the increase primarily due to improved operating performance and net proceeds received from the issuance of common stock in connection with employee stock option exercises. Now I'd like to turn to our financial guidance for 2024. Today, we are reiterating our 2024 guidance that was updated on our Q2 earnings call. We anticipate combined net product revenues for our four commercial products will be within a range of $1.575 billion and $1.65 billion. Our collaboration and royalty revenue guidance range is $575 million to $650 million. And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range of between $1.775 billion and $1.875 billion. Let me now turn from financials and discuss some key goals and upcoming milestones for late 2024. We announced that we'll present additional findings from the ongoing Phase I study of ALN-TTRsc04 in patients with ATTR amyloidosis at the American Heart Association Scientific Sessions in November. We plan to share our Phase 3 development plan for ALN-TTRsc04 in the first quarter of 2025. We also intend to initiate a Phase 2 study for mivelsiran in patients with Alzheimer's disease at or around year-end. Let me now turn it back to Christine to coordinate our Q&A session. Christine?
Christine Lindenboom: Thank you, Jeff. Operator, we will now open the call for questions. Those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have any additional questions.
Operator: Thank you. [Operator Instructions] And we'll take our first question from Ellie Merle with UBS. Your line is open.
Ellie Merle: Hey, guys. Thanks for taking the question. Just in terms of your earlier-stage pipeline, can you elaborate a bit on some of the work that you've done to improve the ability to deliver RNAi to adipose tissue and muscle? And how are you thinking about what makes the most sense as initial targets or diseases in these tissues? And any specific advantages to your approach versus other modalities? Thanks.
Pushkal Garg: Yes. Thanks, Ellie. As Jeff highlighted, we've talked about, we are very excited about the emerging profile of RNAi therapeutics, right? What we're seeing is that these therapies appear to be well tolerated, and we can get sustained knockdown of a disease-causing protein that allows for infrequent administration. And we're guided by human genetics in terms of the diseases that we pursue, which can allow us to validate both efficacy and safety using population genetics as well as preclinical work. So adipose and muscle are two of the areas that we've highlighted in our 225 strategy as new tissues to pursue. We highlighted a little bit at R&D Day earlier in the year, some of the approaches that we're taking, and we remain on track to progress those. We actually are - we'll be talking about an R&D Day early next year, and we'll give the specific timing of that. And that's probably the best time for us to give a more substantive update on those programs. But we're making good progress. And for competitive reasons, we're probably not going to say a lot more at this point.
A -: Thanks, Pushkal. That's great. And I think it's one of the opportunities of our platform really is to continue delivering ongoing innovation as we start to make progress in some of these extrahepatic issues. Thank you, Ellie. Next question.
Operator: Thank you. We'll take our next question from Gena Wang with Barclays. Your line is open.
Gena Wang: Thank you for taking my questions. I wanted to ask one question regarding the ALN-HTT02. It seems like very impressive data in nonhuman primates. I believe this is one of very few showing actual knocking down in nonhuman primate brains instead of most of others showing rodent brain. So I know everyone is using 50% as a benchmark. Is that something you are looking for? What else you will be looking for regarding the Phase 1 data?
Pushkal Garg: Yeah. Thanks, Gena. I'm glad you highlighted the Huntington's program because it's one that we're particularly excited about. This now represents our third CNS program that we're moving into the clinic. And what we're seeing here is that many of the insights that we learned from our APP program in terms of being able to have sustained knockdown of a disease-causing gene and appears to be well tolerated in preclinical studies is very encouraging. So we believe we will have something that will allow sustained knockdown as well as hopefully be well tolerated in the clinic as we've seen with our APP program to date. The nonclinical findings were actually quite benign in the preclinical studies that we saw, as we highlighted in the slide, it was well tolerated both in rodent and nonhuman primate species. And then the targeting approach we're taking is quite unique. We're going after an upstream portion of the gene, which includes the exon 1 fragment. And there's been an emerging amount of data in the literature that suggests that beyond targeting the full-length mutant protein that targeting the exon 1 fragment may also help in progression of this otherwise very, very rapidly progressive and fatal disease. So we think we may have an opportunity for unique efficacy with this molecule. So we're moving forward in our single ascending dose study. These are in patients with symptomatic disease. We'll be looking at safety and tolerability, PK, PD, we'll be looking at changes in mutant Huntington's level - mutant Huntington levels. And we'll also have in that, as we go forward, clinical and imaging and biomarker measures, measures such as NfL, et cetera, that can be very useful in looking at progression in this disease. The study is in active start-up mode in the U.K., Canada. And then in the United States, we also have a green light to proceed. I'll note that we do have a dose cap in the United States. And so we still have a green light to proceed in all three territories, and we're moving forward. So I'm very excited that we'll be able to do that. And we'll work with the FDA going forward if and when we need to sort of lift that dose cap. It may give us enough coverage as it is to cover the doses that we're interested in, but we'll work with the FDA in terms of lifting that dose cap over time. And so we're very excited about this program.
Yvonne Greenstreet: Okay. Next question.
Operator: Thank you. We'll take our next question from David Lebowitz with Citi. Your line is open.
David Lebowitz: Thank you very much for taking my question. In terms of polyneuropathy at this point in time, how would you say the impact of a second silencer has been on the market and your overall trajectory? And additionally, I know that plenty of your prescribers for polyneuropathy are cardiologists. Have you noticed an inflection in the number of questions coming regarding the ATTR cardiomyopathy data?
Tolga Tanguler: Hi, Dave. Yeah. Look, I mean, now we have 9 months under our belt with another competitor in the marketplace in the United States. And what you will see in our - both our quarter-over-quarter growth in the U.S., which is 8% up, as well as our year-over-year growth that is 37% up is a good indicative actually not only how this category still there's a significant unmet need, but how we've been able to actually compete versus a competitor. And we believe the fact that our route of administration is quarterly with a number of optionalities in terms of where those patients actually can receive their treatment. The fact that our patients remain on treatment due to this quarterly dosing and our patient services as well as, obviously, what you'll see in our platform that the ability to provide rapid knockdown as quickly as within the first dose at 60% and up to 88% after the second dose are important differentiators, and we believe this is really getting good traction, both with patients as well as physicians. In terms of the cardiologists, the second part of your question, look, we've put established very clear guardrails to make sure that we are promoting compliantly and making sure that the launch is ahead of us, not - we're not in the launch phase. And when there is questions around HELIOS-B, we appropriately address that and triage that with our medical affairs colleagues. But in terms of the number of patients that are coming in with that indication, that would not be something that we would allow as an organization. But overall, again, I'm very pleased with the performance of Q3, and we are seeing - we're continuing to see good robust demand in our polyneuropathy hereditary indication.
Yvonne Greenstreet: That's terrific, Tolga. I think it illustrates that we've actually built a really high-performing commercial engine and we have a compelling profile for AMVUTTRA. So we're very excited about the future. Thank you. Next question.
Operator: Thank you. We'll take our next question from Paul Matteis with Stifel. Your line is open.
Paul Matteis: Hi. Great. Thanks so much. I wanted to ask one more follow-up question just on recent prescribing dynamics in TTR in light of the HELIOS-B data. And Tolga, I totally understand where you're coming from, right, that you guys promote solely in polyneuropathy. But just as it relates to a cardiologist if they want to prescribe AMVUTTRA right now, what are the prior auth requirements that you see? Do they need to have a neurologist offer corroboration of a polyneuropathy diagnosis? Like are there kind of significant impediments in place that really can find this drug to that true mixed phenotype population at this point before getting an expanded label? Thank you.
Tolga Tanguler: Yeah, Paul, that's a great question. And you clearly grasp some of the complications and how the patients are actually getting diagnosed. So if you're in a cardiomyopathy if you're suspected of having a cardiomyopathy, physicians, especially in the United States, tend to go through scintigraphy. And if the patient actually is determined to have the condition as suspected, they would then be quickly put on the treatment. Now in polyneuropathy, not only because of our indication is hereditary that you would actually go to a genetic testing to validate that. And then you would also have an additional neurological workout to make sure that, that patient actually has the neurological manifestations of the disease and then you would be put on the treatment. Now in terms of the access challenges, nearly all of our patients actually end up getting good sustained access regardless of what source of reimbursement channel they have. So that's really not the challenge. It's mostly is - is the challenge on the diagnostic pathway, polyneuropathy hereditary being the last stage of that pathway rather than the first stage what we see in cardiomyopathy.
Operator: And we'll take our next question from Ritu Baral with TD Cowen. Your line is open.
Ritu Baral: Hi, guys. Thanks for taking the question. I wanted to ask just how Tolga and maybe, Jeff, how you are thinking about payer discussions now even ahead of potential label expansion. What are the levers, what are the topics that you're discussing? And how are you viewing the potential for volume-based discounts upon potential label expansion and increasing number of patients on AMVUTTRA?
Jeff Poulton: That's a great question, Ritu. I think it's actually for Tolga.
Tolga Tanguler: Yeah. So Ritu, as we shared at the TTR Day, what payers care as they should be is the value proposition, which is really driven by the clinical outcome. And as we have demonstrated in HELIOS-B, the product really does provide an incredible and important differentiator in terms of CV outcome in today's patient population. So that's what we're so far seeing is payers understanding, acknowledging that this remains a rare, albeit growing disease and the fact that the HELIOS-B results outcomes are compelling. In terms of how we're going to be able to navigate the access landscape has a lot to do with our patient access philosophy. I think what we've been able to demonstrate within the polyneuropathy indication, how we've been able to get seamless access to our patients and a big majority of them not having any co-pay burden and about 30% of them end up having about $2,000 or less co-pay burden. And part of our patient access philosophy has to do with value-based agreements and appropriate rebates. This is an area where, obviously, we're going to be disclosing more. We understand and appreciate why there is interest in this. But we will actually communicate that as we get more closer to our PDUFA date, which is not set yet.
Ritu Baral: Got it. And let me ask very quick follow-up, guys, just on Paul's question. It's a follow-up to Paul's. So I'm going to squeeze this in. How is there how is the cardiologists and neurologists understanding of compressive neuropathies factor into Paul's question?
Yvonne Greenstreet: You mean carpal tunnel or spinal...
Ritu Baral: Carpal tunnel spinal stenosis. Yeah, in that.
Tolga Tanguler: So I mean, yeah. Look, I mean, I think TTR is a systemic disease, and that's why you have multicenters that actually treat multidisciplinary physicians that actually treat this disease. Now this doesn't also, of course, exist in every market, every academic - even every academic center. But in most centers, you have a good collaboration between a cardiologist and a neurologist and in some cases, even orthopedic surgeon. But because the disease has been evolved, the genesis of the disease evolved by the cardiologists, the first stop tends to be the cardiologists where they actually do the scintigraphy and do the preliminary diagnosis. And if there is not suspicion of additional manifestations of disease, they tend to go with the only approved product that's available today. And we believe that's obviously going to change over time.
Yvonne Greenstreet: I think it's a great question actually, Ritu, because these red flag symptoms, I think, are going to be an important part of physician education and awareness going forward. So thanks for the question. The two questions. Let's take the next question.
Operator: Thank you. We'll take our next question from Salveen Richter with Goldman Sachs. Your line is open.
Unidentified Analyst: Thanks for taking our question. This is Tommy on for Salveen. So you talked about how there is this initial focus on frontline for cardiomyopathy. But wondering if - what's your thoughts on if there could be a bolus of path progressors in the second half of next year who are aware and kind of want something new? Thank you.
Tolga Tanguler: Yeah. I mean at our TTR Day, we delayered the strategy. And the reason why we explained that strategy has a lot to do with what the data suggests and where today's patients are. So as we've highlighted, this is a fast progressing and severe disease. So our understanding is the treaters are really focusing to make sure that they - as soon as they diagnose these patients, they want to diag them early and they want to hit hard, hit hard with a product that we believe is going to be providing data with today's patient population, where the subgroup patients where a portion of them are on the only stabilizers that is available or with GLP-1 or they are on diuretic intensification. Those are the patients that they are currently seeing. And if you look at the dynamic of the market, we see ever larger number of patients that are coming into the category. So you want to be able to establish yourself as a first-line product because of the data and because of the fast progress of the nature of the disease, so those patients actually can get treated. Now in terms of patients that might be progressing on a stabilizer, of course, I'm sure physicians will start identifying those patients if they haven't already done so and we'll probably eventually either depending on the access limitations or challenges that they may have, either put them switch them on those patients or use a combination therapy. Now it's important to highlight that until tafamidis will become generic, there is no switch behavior that's been established in this category. Therefore, we do believe that will take some time to establish. And obviously, we will be doing our part to make sure that those patients are identified, those patients that are progressing are well identified. But I think it's important to highlight that given the number of patients that are coming into the category and the dynamic and the data that we have, we believe AMVUTTRA will be well positioned to become a first-line standard of care therapy.
Yvonne Greenstreet: Thanks, Tolga.
Tolga Tanguler: Assuming approval of [indiscernible]
Yvonne Greenstreet: Thank you for answering that question. Next question.
Operator: Thank you. We'll take our next question from Jessica Fye with JPMorgan. Your line is open.
Jessica Fye: Hey, guys. Good morning. Thanks for taking my question. I got another one on TTR. Is there anything that you're going to be watching for in the acoramidis label with their PDUFA coming up? And I guess, stepping back, do you see any of the potential label scenarios for that product as relevant to your expectations for your own launch in TTR cardiomyopathy? Thank you.
Tolga Tanguler: Yeah. Look, like everybody, obviously, we're interested in seeing the acoramidis label assuming approval. I mean, we feel very confident about the data that we've generated with HELIOS-B. And we're looking forward actually to moving through the regulatory process in both the U.S. and in Europe and using our priority review voucher, assuming a potential approval early next year. So we feel really good about where we are. And I think we'll just have to wait to see exactly what gets delivered with respect to acoramidis.
Pushkal Garg: Yeah. The only thing I would add is, obviously, to comment on their label would be speculative. But from a broader market dynamic perspective, we believe acoramidis will be a twice daily stabilizer. And how that market dynamic will shape, I think we'll have to do a lot to do with our orthogonal mechanism of action and how we would be able to compete in the patient population that are still, again, as a first-line agent or those patients that are progressing on a stabilizer.
Yvonne Greenstreet: Terrific. Thank you. Next question please.
Operator: Thank you. We'll take our next question from Gary Nachman with Raymond James. Your line is open.
Gary Nachman: Thanks. Good morning. So as we anticipate the launches of vutri and ATTR-CM next year in both the U.S. and then the EU, how should we think about spending levels in SG&A relative to this year for all the commercial activities you'll be doing, just order of magnitude? And then remind us of the infrastructure you have in Europe and how you think of the CM opportunity there relative to the U.S. in terms of both accessing patients and also pricing? Thanks.
Yvonne Greenstreet: That's a great question. Thank you. I think Jeff will take the first part of it, and then Tolga will follow up with his plans for making sure that we kind of execute on our plans for potential AMVUTTRA launch.
Jeff Poulton: Yeah. I mean, I would say we upgraded our guidance this year at Q2 on OpEx, right? And that reflected the confidence that we had in the HELIOS-B results and sort of playing to win. And so you'll see in the second half of the year this year an increase in investment. And the commercial team has made very good progress in starting to prepare for the launch, particularly in the U.S. with the hiring that's been done. So with a lot of that happening in the second half of the year, that's obviously going to create growth for next year. And we'll continue to invest more broadly even than just in the U.S. as we move towards the second half of the year and launches in Europe. I don't have specific guidance, but I would expect that certainly double-digit growth in terms of SG&A. But we'll provide our annual guidance for '25 on our year-end call in February.
Pushkal Garg: Yeah. And what's been great is that we've actually built a very strong foundation actually in TTR polyneuropathy. And so really, it's been more of a sort of incremental growth to make sure that we're absolutely well positioned to be successful in the CM indication. But Tolga, anything else to...
Tolga Tanguler: I mean, the only thing I would add is from an organizational focus perspective, we have established an end-to-end organization, which has actually demonstrated excellent results, not only in TTR, but also in rare. So our TTR organization, not only in Europe, but also in Japan, has been demonstrating really robust growth numbers. I mean we've just posted a 31% year-over-year growth. If you look at the performance of - on the demand side of our international business has been up at 6% quarter-over-quarter. Now that's been done in a market where there is significant price sensitivity, where we have a PN product that's priced for the narrower indication. And we've been able to become a market leader at 80% versus tafamidis in that specific PN indication where we also compete with them in that indication. So we actually are quite pleased with the structure that we've established and as Jeff indicated, we're going to play to win and make sure that we are providing the right access options in those markets. And so far, we've been able to compete well, and we believe we'll be able to do that with the HELIOS-B data as a tailwind.
Yvonne Greenstreet: Great. Thank you, Tolga. Next question.
Operator: Thank you. We'll take our next question from Kostas Biliouris with BMO Capital. Your line is open.
Kostas Biliouris: Good morning, everyone. Thanks for [Technical Difficulty] and outside of your pipeline, acknowledging that your pipeline is large and very robust and can drive growth. I'm wondering whether you can comment on potential BD activities that could potentially support even additional growth in addition to your internal efforts? Thank you.
Tolga Tanguler: Yeah. No, that's a great question. Look, we're very privileged actually to have kind of an incredibly rich pipeline. I mean we think it's one of the most exciting pipelines in the industry. And Pushkal touched on the fact that we'll be doubling the pipeline by the end of '25. So we've got a lot of really, really interesting opportunities in the company. And clearly, we're also going to make sure that we focus on a successful AMVUTTRA launch. And so we're really focused on driving both our internal pipeline, as well as continuing to optimize the platform. When we think about BD, we're also very open to considering opportunities that really enable our platform and help us continue to access all the other tissues, and Pushkal described some of these. And so really, that's our focus at the moment. Clearly, we obviously pay a lot of attention to what's happening in the innovation landscape around us. But really, we have - we're in a very privileged position to have an awful lot that we can progress within the company, and we're excited to move all of that forward.
Christine Lindenboom: Next question. I think this is our last question.
Operator: We'll take our last question from Tazeen Ahmad with Bank of America. Your line is open.
Tazeen Ahmad: Great. Thank you for squeezing me in. Maybe this last one is for Tolga going back to the launch. In terms of expectations, for the early part of any rare disease launch, I think companies talk about the time it's going to take from the time the script is written to the time that the script is dispensed to the patient. But since this is going to be the second indication for your product, do you expect those traditional sometimes conservative time lines as to extended time period, at least initially to hold true here? Or do you expect that to already have been smoothed out from your PN launch? Thanks.
Tolga Tanguler: Yeah. Thank you, Tazeen. We recognize that this is an area where we do need to provide some additional color. And we will do that closer to our launch time lines and the respective engagements that we will have, and we should be able to provide additional context as we get closer to the launch.
Christine Lindenboom: Thank you, Tolga. And look, thank you to everyone for joining us on the call. We feel very pleased with the third quarter of 2024. It was one of continued progress. We delivered robust financial growth as well as advancements in our pipeline. So thank you, everybody, and have a great day.
Operator: That concludes today's teleconference. Thank you for your participation. You may now disconnect.
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Source: Investing.com
