BridgeBio Pharma - Earnings Call - Q1 2025
April 29, 2025
Transcript
Operator (participant)
Good afternoon. I will be your conference operator today. All lines have been placed on mute to prevent any background noise. After the company's remarks, there will be a question-and-answer session. If you would like to ask a question, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, please press star one again. Thank you. Before we begin, I would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities laws, including but not limited to statements about BridgeBio Pharma's future operating and financial performance, business plans, prospects, and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward-looking statements.
For a discussion of these risks and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. With that completed, BridgeBio, you may begin your conference.
Chinmay Shukla (VP of Strategic Finance)
Good afternoon and thank you for joining BridgeBio's Q1 2025 earnings conference call. This is Chinmay Shukla, VP of Strategic Finance at BridgeBio. Today, we will discuss our financial results for the first quarter of 2025 and provide an overview of how we measure success in our business. We'll provide insight into the early results from the launch of Attruby, as well as provide an update on our pipeline, which has three phase three readouts expected in the next year, including our efforts in expansion indications such as in chronic hypoparathyroidism. Today's call will feature Neil Kumar, Chief Executive Officer; Matt Outten, Chief Commercial Officer; and Tom Trimarchi, President and Chief Financial Officer. For the Q&A portion of the call, Ananth Sridhar, Chief Operating Officer of BridgeBio Cardio Renal, and Justin To, Chief Executive Officer of BridgeBio Skeletal Dysplasia, will also join.
Following the remarks by our team, we will open up the call for Q&A. With that, I'll turn the call over to Neil.
Neil Kumar (CEO)
Thanks to everyone on the line for the time, and welcome to our first earnings call. We're grateful to open up another dimension of our dialogue with our investor partners. You've collectively allowed us to deliver for the patients we serve, and we look forward to your feedback on how to continually improve our discussion in this setting. Today, we know the star of the show is the Attruby launch, and the good news is that the brand is delivering for patients and the business. $36.7 million in revenue this past quarter suggests that clinicians and patients are resonating with our differentiated clinical efficacy, safety, and accessibility. We continue to educate on our therapeutic impact, which comes as early as three months, with a 42% relative risk reduction on cardiovascular hospitalization and mortality at 30 months, including a 50% reduction in cardiovascular hospitalization at that same time point.
All these best-in-class point estimates are available at the lowest price point in the marketplace. There is much to like there, and we're aware that there's much work yet to be done. You'll hear about some of that work today as it pertains both to commercial tactics and further development work. We add to Attruby's good news the continued progress across our pipeline of three additional blockbuster products. Our trials in limb-girdle muscular dystrophy type 2i, achondroplasia, and ADH1 remain on track with low dropout rates, frequent data collection, and positive site audits, all in preparation for an efficient NDA submission should the data be positive. Furthermore, key additional markets are being opened up. Our hypochondroplasia trial enrolled with incredible speed, and we now have first patient in there.
Our work with encaleret in the hyperparathyroid setting positions it well for a registrational trial, which, if successful, could pave the way for the first oral compelling solution in that space. Before we move to discussion into further specifics regarding the business, and since this is our first time hosting this type of call, I wanted to briefly address how we measure the performance of our business on an ongoing basis. It's nice that this quarter was a success, there will be harder quarters, I am sure. Through it all, you should expect for us to communicate consistently and in terms of net gains or losses in NPV. For instance, in this last quarter, our NPV increased by 9%, given changes in the following variables. Number one, the time factor of money, especially given the late stage of our portfolio.
Number two, a higher and anticipated revenue driven by a faster uptake of Attruby than we anticipated, and likely a slightly higher peak year share by volume than our market research had projected. Third, the success of our small study in HP and other sponsored setbacks in the space of oral HP medicines. Fourth, the early enrollment of our run-in of our hypochondroplasia study, moving our timelines in for that program. And fifth, the slight decrease in our modeled cost of capital, given our recent convertible offering. There were NPV drags, most prominently including tariffs; however, these have a close to negligible effect at less than 1% of our overall NPV.
Stepping back from NPV, and as a reminder, our overall objective here at BridgeBio is simple: to maximize the positive change we can have in terms of quality-adjusted life years for the patients that we serve as quickly as possible. We do so by creating as many meaningful medicines as possible as quickly as possible within three constraints. The first is that each program must have beautiful science, which in our vernacular means a high PTS driven by understanding a mechanism of disease, optimally paired with a therapeutic mechanism of action that targets a well-described genetic condition at its source. These types of programs historically have a three to four times higher probability of technical success than all-comer drug R&D efforts. Over time and many programs, this elevated probability of technical success moves us from being a speculative lottery ticket to being something akin to an engineering company.
The second constraint is that we strive for each medicine that we make to be first-in-class or best-in-class. Determining best-in-class can be tricky in the absence of double-blind head-to-heads, but we approach this using a straightforward Bayesian approach. For instance, in TTR, if faced with decision as to what drug to use, a logical person would first interrogate the salient endpoint, death and hospitalization, at a common time point. In this case, at 30 months, a relative risk reduction of 42% is a better point estimate as compared with any of the other products in this marketplace. You would then ask, how quickly does each drug take action? You would find that the three-month beginning of separation between placebo and active is the earliest point estimate of timing of impact in this field. Logically, Attruby is at worst, no worse than other medicines.
You would then look at safety. Here you would find little difference between small molecules, but would observe that they do not have the safety signals some knockdowns have: vitamin A deficit, which, by the way, turns knockdowns into a once-daily pill regimen, injection site reactions, the absence of impact on AFib, whereas both small molecules had meaningful reductions there, the imbalance of cardiac SAEs as observed in the Onpattro study, and the as-of-yet unexplained imbalance in death on the Revusiran trial.You couple that with the overall finding that across multiple studies, TTR is a cross-species conserved protein, and that ever higher levels of TTR lead to ever longer lives and less disease over time. Logically, small molecule stabilization from these data is the safest approach. Finally, the logician might look at price only to discover that Attruby has the lowest price point.
We believe, given all of that, the choice is clear. We apply similar reasoning in other competitive spaces like achondroplasia. Our final constraint is that each program we work on should be NPV positive to ensure firm-level sustainability. We use all available levers during the R&D stage to optimize NPV, including time, cost, cost of capital, and probability of technical success. The better our model is at generating economic value from projects, the further we can push into markets where others cannot extract adequate value in addition to being a better owner of obviously NPV positive projects. The fact that we will spend well under $100 million per program to get each one of our potential blockbusters from the pre-clinical stage through proof of concept sets us up well for future growth that is economically attractive. Okay, so that's our overall objective function with its attendant constraints.
You heard the first and most important frame that we use to think about the business, which is NPV. There are other frameworks that we also use to look at the business: understanding the business by stage and capability, research, development, and commercial; understanding the business in the context of the overall ecosystem; and understanding the business program by program. Using the by-stage framework first, and as I mentioned earlier, we are pleased with the ongoing progress of our commercial launch and the building of a sustainable competitive advantage there, which means, of course, that our group is able to extract more profit from the asset than another would be able to. I have also touched already on our ongoing development wins. On discovery, our bread and butter, we continue to advance programs in genetic dilated cardiomyopathy and ADPKD. We also hold significant stakes in BridgeBio Oncology Therapeutics and GondolaBio.
In the latter, we expect phase two data in our EPP program later this year, and we expect to generate up to six development candidates in 2025. From an ecosystem framing, the substrate for making genetic medicines remains incredible. We see that in the progress GondolaBio is making, and more broadly with the depth of genetic disease starting points being produced and accessible at low price points. Finally, at a program level, Matt will have more to say about our commercial launch of Attruby. Our goal there, as a reminder, is $4.3 billion in peak year sales, or about 30% of a $15 billion marketplace. That gets delivered against approximately $380 million of spend on the brand per year.
Almost 25% of current spend is on further research and development activities like Act Early, which we think could continue to improve our medicine's positioning and its ability to help patients in later years. The product of this spend also includes salient results like our variant data, where we obtained a hazard ratio of 0.41 with a p-value of less than 0.02 in the sickest of patients. New work we are doing regarding AFib, which is an emerging marker of disease progression, the first results of which we plan to present at ESC later this year. For infigratinib, a first-in-class oral FGFR3 inhibitor in development for both achondroplasia and hypochondroplasia, the pivotal PROPEL 3 phase three is fully enrolled, and we expect last participant last visit by the end of this year.
We have also reached regulatory alignment with the FDA on our clinical development plan for infigratinib in children with achondroplasia from ages zero to three, and we expect to initiate clinical development in this important age range by the end of the year. Excitingly, we have also enrolled the run-in for our phase two hypochondroplasia trial well ahead of benchmarks. For encaleret, a negative allosteric modulator of the calcium-sensing receptor, our phase three CALIBRATE study is fully enrolled. We expect last patient, last visit, and top-line results in the second half of this year. In parallel, encaleret is also being studied in hypoparathyroidism, and we announced today positive POC data for encaleret in this key expansion indication.
Preliminary evidence in the ongoing POC study has demonstrated that 78% of the first nine study participants were able to achieve normal blood and urine calcium levels within five days of encaleret administration. Moving to BBP-418, an oral first-in-class disease-modifying therapy in phase three development for treatment of individuals living with limb-girdle muscular dystrophy type 2i. We have fully enrolled four to five of phase three registrational placebo-controlled study evaluating the safety and efficacy of BBP-418. The study includes a planned interim analysis to 12 months focused on assessing a surrogate endpoint biomarker, glycosylated alpha-dystroglycan, to support accelerated approval in the United States. We anticipate top-line readout from that phase three interim analysis second half of this year as well. Finally, BBP-812 is an AAV9 gene therapy in development for Canavan disease, an ultra-rare neurodegenerative disease that usually leads to death in the first two decades of life.
Here, we are pursuing an accelerated approval approach using a single seamless registrational trial to bring this potential therapy to children with Canavan as quickly as possible. A meeting this month with the FDA reinforced the validity of our approach, which centers around the use of urine NAA in tandem with other clinical measures and the suggested BLA filing that we have laid out by end of 2026. While this is not a very prevalent disease, we believe it's a great example of our model, targeting the disease at its source and operating leanly to enable us to go after a well-validated condition in an NPV-positive manner. Okay, that's the final framing. To wrap up my comments, BridgeBio is executing well and importantly possessed of a tremendously strong foundation for the future. Number one, an unmatched collection of late-stage genetic disease businesses with favorable economic prospects.
Number two, a cadre of outstanding managers that are dedicated to their specific assets business and to BridgeBio. Number three, a diversity of stakes, including wholly owned assets and significant stakes in GondolaBio and BridgeBio Oncology Therapeutics. Number four, first-choice ranking with many academics when seeking a partner to discover and develop new medicines. Number five, a culture that is distinctive from most biotechs I have seen and that is decentralized, independent thinking, and lives the value that every minute counts for the patients we serve. We're excited to work with you, our investors, to continue to build this company and to keep you up to date on our progress for patients. With that, I'll hand it over to Matt to walk through Attruby's commercial performance in more detail.
Matt Outten (Chief Commercial Officer)
Thanks, Neil. To add to your comments, the launch of Attruby is off to a strong and encouraging start.
Let me walk through some of the highlights in terms of what we are seeing out in the marketplace and what we think is driving the rapid momentum we've built in just a few short months. The first highlight is the early uptake across all major prescriber and patient segments. As shared in our press release, 2,072 unique patients have received a prescription for Attruby through April 25th, and 756 unique healthcare providers have written at least one prescription. This early adoption spans all physician segments, including large academic centers, regional amyloid clinics, high-volume heart failure specialists, and community cardiologists. Importantly, we're seeing Attruby used across the full spectrum of patients: wild-type and variant, newly diagnosed, as well as switches from partial stabilizers.
The fact that these different patient types are all gaining timely access and that prescribers are already writing for multiple patients gives us confidence that we're building a strong foundation for Attruby. Let's discuss what is driving the uptake. It comes down to strong clinical endpoints paired with our transparent patient-first support programs. Starting with the clinical data, Attruby is the only therapy for ATTR-CM that has demonstrated a separation from placebo in as early as three months. No other medicine has demonstrated that, and it's not just about efficacy. Attruby also positively impacts KCCQ scores, which directly correlate with better quality of life for patients. That's resonating deeply with physicians who want to make a meaningful impact on their patients' daily lives and patients who want to keep their functional activity levels. Second, let's look at hospitalization rates.
Attruby is the only ATTR-CM therapy to demonstrate 50% relative risk reduction in cardiovascular hospitalization rates. This includes a statistically significant reduction in composite mortality and hospitalization in the variant ATTR-CM population, a subgroup widely regarded as among the most difficult to treat. This was highlighted in the recent variant subgroup data presented at ACC. Third, affordability. Attruby is the most cost-effective therapy in ATTR-CM available: 10% less expensive than tafamidis and 50% less expensive than vutrisiran. It's not just about the WAC price, though. Attruby has a free trial program for all patients, regardless of insurance status, and lifetime-free drug for patients who participated in our pivotal trials. That matters to physicians, patients, and payers, especially when coupled with the three-month onset of treatment effect and 50% reduction in cardiovascular hospitalization at 30 months. No other ATTR-CM therapy checks all of these boxes.
BridgeBio has a commercial model that is different, and it's working. Attruby will be followed by three additional commercial launches in 2026 and 2027. What really differentiates BridgeBio, though, is how we bring products to market. There are no convoluted value-based contracts, no vague promises of future rebates contingent on volume thresholds. What we offer is simple, transparent, and built around the people who matter most: patients and their care teams. We are hearing from the field that this clarity, paired with strong clinical data, is helping accelerate adoption. Once an HCP decides to prescribe Attruby, we make it easy to get the medication to patients. Patients can receive Attruby within 48 hours. We have two world-class specialty pharmacies in the Attruby network and also allow physicians to fill prescriptions in their own in-house pharmacies. All of this investment is paid off.
We are gaining share in the crucial first-line setting, and our conversion to paid rate and time to paid prescription is well ahead of industry benchmarks. Looking towards the future, our focus heading into the rest of the year is as follows: continue marching towards our long-term goal of 30-40% share of the ATTR-CM market and increase share in the critical first-line setting, which is a leading indicator of launch success. While these early signs are encouraging and they reflect not just the strength of the product, but the preparation and the commitment of the broader BridgeBio team, we are also excited about what's ahead and remain focused on reaching as many patients as possible as quickly as possible. With that, I'll turn it over to Tom for a review of the financials.
Thomas Trimarchi (President and CFO)
Thank you, Matt, and good afternoon, everyone.
Q1 2025 marked BridgeBio Pharma's first full quarter of net product revenue from the Attruby US commercial launch, a major milestone for the company and a significant step forward in our evolution into a fully integrated genetic medicine business. I'll now walk through the financial highlights for the first quarter of 2025. Please note that our commentary in today's call will focus on GAAP financial measures unless otherwise indicated. Total revenues were $116.6 million for Q1 2025 and consist of Attruby net product revenue and license and services revenue. Attruby net product revenue was $36.7 million, driven by strong demand across all major prescribers and patient segments. License and services revenue was $79.9 million in the quarter, primarily driven by the recognition of the $75 million regulatory milestone related to Attruby's EU approval.
Also in Q1, we received Attruby approval in Japan, for which we expect to recognize a $30 million milestone in the second quarter. Total operating expenses for the first quarter of 2025 were $218.4 million, compared to $210.2 million in the same period last year. This increase reflects our continued investment in the Attruby brand and our advancing late-stage pipeline. Included in our total operating expenses was $29.4 million in stock-based compensation expense, compared to $28.9 million in the first quarter of 2024. Looking forward, we expect only modest growth in quarterly operating expenses for the remainder of the year, with an offset to total cash burn provided by Attruby sales in the US and Attruby ex-US. R&D expense for the first quarter of 2025 was $111.4 million, compared to $141 million in the same period last year.
This decrease was largely due to the strategic carve-out of our oncology business and early-stage research programs, allowing us to focus resources on the Attruby launch and late-stage pipeline. SG&A expense for the first quarter of 2025 was $106.4 million, compared to $65.8 million in the same period last year. This increase was driven by the full-scale commercial rollout of Attruby, including field team deployment, payer engagement, and patient support infrastructure. Restructuring expense for the first quarter of 2025 was $0.6 million, compared to $3.4 million in the same period last year. We ended the quarter with $540.6 million in cash and cash equivalents, which does not include $105 million in regulatory milestone payments anticipated in Q2 for ex-US approvals of Attruby. We believe we are well-financed to support the continued execution of the Attruby launch and deliver on key milestones from the pipeline this year.
We look forward to sharing additional commercial updates throughout the year and the top-line data from our three phase three programs over the next year, with ADH1 and LGMD2i in the second half of 2025 and achondroplasia in early 2026. With that, I'll turn the call back to Chinmay.
Chinmay Shukla (VP of Strategic Finance)
Thank you, Neil, Matt, and Tom. I'll now hand it back to the moderator to open the line for questions. I would like to request our analysts to limit themselves to one question each so that more people get a chance to ask their questions.
Operator (participant)
At this time, we'd like to remind everyone in order to ask a question, please press the star button followed by the number one on your telephone keypad. We'll pause this for a moment to compile the Q&A roster. Your first question comes from the line of Salim Syed of Mizuho. Please go ahead.
Mani Foroohar (Senior Research Analyst)
Great. Congrats on the quarter, guys, and congrats also on your first earnings call. Maybe just one for Neil or Matt here. Obviously, the quarter came in healthier than I think people had thought going into the print, and I appreciate the commentary that you provided, Matt, on some of the dynamics there. Any sort of granularity you could provide on the tailwind and what you really deemed that's working well for you here?Thank you.
Neil Kumar (CEO)
Yeah, maybe I'll kick it off. Thanks, Salim. It's probably too early for some of the higher-cost commercial tactics that we've invested in to show ROI right now. Hearteningly, I think a lot of the demand we're seeing to date really is a product number one of the differentiated clinical efficacy we have.
As a reminder, and you know this, the earliest separation and point estimate that we've seen in the field at three months, 42% relative risk reduction against ACM and CVH at 30 months. Again, the best point estimate we've seen at 30 months, coupled with that 50% reduction in hospitalization, which turns out to be a hugely meaningful measure for patients who both want to live longer but also live healthier. I'd say that's point number one. Point number two, as you saw as well from the Pfizer call this morning, continued market growth, right? We're one-fifth diagnosed in this space, some 50,000 or so patients diagnosed. We think there's 250,000 to 300,000 in the U.S. alone. Physician education, coupled with there being a variety of therapeutic interventions now available, I think is driving that growth. That, I think, is another tailwind.
The third is the access programs that Matt talked about. The team, I think, has done a terrific job of ensuring that patients, when they are prescribed Attruby, can get the medicine and stay on the medicine as long as they need to. Those would be the three salient drivers. I'd say the final thing is a little bit of what a physician described to us the other day as karma. Obviously, we're the only sponsor in this space that gave free drug for life for their trial participants. Unfortunately, others decided not to. We're also the only sponsor in the space running a primary prevention study, which I think many physicians view as the ultimate in trying to catch patients in this mass action condition as early as possible to do as much as we can for their conditions.
Those types of things, I think, over a long period of time will stand us in good stead as a sponsor here in a competitive space. I don't know, Matt, if you'd add anything.
Matt Outten (Chief Commercial Officer)
No, I think to miss the people. We've spent a lot of time putting the team together, both internal and out in the field, to make it as easy as we can for both prescribers and for patients. I think you're seeing the good results of that.
Mani Foroohar (Senior Research Analyst)
Great. Thanks, guys. Congrats again. Thanks, Neil.
Operator (participant)
Your next question comes from the line of Tyler Van Buren of TD Cowen. Please go ahead.
Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)
Hey, guys. My congrats on the stellar Attruby result as well and the ongoing progress of the pipeline. Again, the $37 million of Attruby sales far exceeded expectations.
When you say that the paid conversion rate is well ahead, can you help quantify that? Was the time to paid quicker than a month for some patients? And how much stocking was there in the quarter?
Neil Kumar (CEO)
Yeah. Hey, Tyler, great to hear from you. Thanks for the question. I'm going to pass it on to Matt to comment more on conversion.
Matt Outten (Chief Commercial Officer)
Yeah, thanks for the question. We're really happy with how conversion is tracking. That's for both free trial to paid and also commercial prescriptions to paid. Everything regarding conversion is consistent or better than historical launches that we've studied. I will just point out a free trial acts like a normal prescription. An HCP writes it, the pharmacy processes it, and the patient gets it. We designed our network specifically with conversion in mind, and that's what makes the access so easy.
Our goal remains the same: 30-40% peak share. It takes about three to six years usually to hit. We're hoping we can do that a little bit faster. In regards to your channel and inventory question, I mentioned we do have a limited distribution network that allows for very frequent ordering, and it allows our customers, our distributors, to have just-in-time inventory. There is no need for them to really hold large quantities. Typically, I would say that this small group of distributors holds about one to two weeks of inventory.
Thomas Trimarchi (President and CFO)
Hey, Tyler, this is Tom. Let me just put a finer point on the inventory question. As I mentioned in the prepared remarks, the sales in the quarter are primarily driven by demand. We have seen only a minor impact of inventory on total sales in the quarter. It is really demand-driven here.
Neil Kumar (CEO)
Yeah, thanks, Tyler.I know you had another question. Happy to answer more about this or go to your next question.
Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)
Nope, that's great. Thank you.
Operator (participant)
Your next question comes from the line of Mani Foroohar, of Leerink Partners. Please go ahead.
Mani Foroohar (Senior Research Analyst)
Hey, guys. Congrats on the quarter. Clearly, it blew out expectations despite having shown pretty good scripts repeatedly. I want to dive in on the script numbers. I'm looking at the incremental scripts on a weekly basis. Through that first update on January 10th, it was in the 60s per week. Through the update you gave on an incremental basis on February 17th, that was running north of 100 scripts a week.
Again, running through from 12 and 4 weeks into launch and the 22 weeks into launch, i.e., from February 17th to April 25th, you're still running at about 110, 109 scripts per week as reported. I know that's just math, and there's a lot of nuance that goes into script reporting. Could you give us a sense of what the sort of character and velocity of new patient scripts that you're seeing right now, and sort of what is the kind of direction of travel there? I have a follow-up question.
Neil Kumar (CEO)
Great. I can take that. Thank you for the question. I mean, I think starting out, the thesis really, again, it remains unchanged. TTR levels go up with Attruby, and it's the only near-complete stabilizer on the market.
When we sort of take that thesis and then dive into, okay, what's happening, and then how do we think that's going to impact things going forward? The month-over-month growth rate in the treatment naive section has been very strong, and that's been across all segments. This is in the large centers. This is in the community. It's across all types of patients, variant, wild type. There hasn't been sort of one area or another that's done better. We've sort of seen this across the board. When we look at sort of the two groups, we have the treatment naive patients. That's our focus. That will continue, we believe, to grow over time as it has been. Then you have the switch patients.
Of course, when we launched, we had 100% of the switch share because we were the only option you could switch to. As now with new entrants in the market, that's going to evolve over time because there are now more choices. I think that the data and how we report will evolve over time as well based on that. That's kind of where we are and how we see it moving forward.
Mani Foroohar (Senior Research Analyst)
Great. That's helpful. I have sort of a non-PPR question to everyone's surprise. When you think about limb girdle data coming later on this year, which obviously we've been discussing a number of calls, this is not the first time you guys have brought it up.
We talked about it at my conference a couple of years running about the fileability of that data set or whether a later data set from the same study will be required. Do any of the changes at FDA concern you around your ability to file on a biomarker? Do you think you have to show a distinct level of clear clinical improvement on a non-biomarker/functional basis? Where are we in terms of the fileability on that biomarker for limb girdle?
Matt Outten (Chief Commercial Officer)
Yeah, I can take that. Mani, we haven't met with the agency of late on the LGMD2i program, but we have had some close to 10 meetings now over the course of the last month as it pertains to either pipeline at GondolaBio or pipeline here at BridgeBio. Probably the latest meeting was in and around the Canavan program.
I have seen nothing but, I would say, a positive inclination toward trying to get first-in-class medicines that target pathomechanism like our drug for LGMD2i onto the marketplace as quickly as possible to benefit the children that are suffering from these conditions. I do not think the rather clear guidance that we have gotten from the agency to date in and around fileability around glycosylation of ADG is going to change. I really do not. I have been on the record saying I think it is going to be a problem if we go the right way and hit our primary endpoint on ADG, but we go the wrong way on all clinical measures.
Obviously, I don't think that's going to be the case based on what we observed in phase two, which was albeit an open-label study against natural history where we saw improvements in measures of ambulation and other clinical outcomes. I do believe these things will move toward the positive, or at least a few will move toward the positive. Obviously, modified North Star, North Star, which has historically been the gold standard in these conditions, it's all noise over the course of the first 12 months. Whether the point estimate goes one way or the other, I think natural history has made that very clear. That is why we're running the confirmatory trial. This is effectively a nested trial design that goes on for another two and a half years post the readout later this year.
I mean, long story short, yeah, we continue to believe that this is going to be an improvable endpoint in terms of ADG glycosylation increase.
Mani Foroohar (Senior Research Analyst)
Awesome. Thanks, guys.
Neil Kumar (CEO)
Thanks, Monica.
Operator (participant)
Your next question comes from the line of Tyler Van Buren of TD Cowen. Please go ahead.
Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)
Hey, guys. Yeah, I just had a second question that I meant to ask, but just the ADH1 and limb girdle phase three is reading out there in the second half of the year, clearly have a high probability of success. So it'd be great to hear you elaborate on why investors should be excited about, and more importantly, focus on those opportunities beyond the ongoing Attruby launch. What do you think the magnitude of those opportunities could be?
Neil Kumar (CEO)
Yeah, good question, Tyler.
As I was suggesting, we continue to be heartened by both the clinical operational positioning of LGMD2i, ADH1, and our achondroplasia trials, as well as the potential to help a broad swath of patients. I think from an investor standpoint, one has to consider the sheer size of these marketplaces. LGMD2i, as we've discussed, some 7,000-8,000 patients between the US and EU. That's a substantial market size as compared to many of the other muscular dystrophy programs that you see out there at the price points that are attendant in the space. With ADH1, a rather much more prevalent condition, maybe 10,000-12,000 patients in the United States alone, as suggested by statistical genetics methodology, some 4,000 or so already identified to date. That's going to be really a program associated with the market build and finding new patients.
We have already shown that we can do that in some of the sequencing efforts we have undertaken within the non-surgical hyperpara community, where we are reliably finding something like 20%-25% of patients actually harbor the gain-of-function mutations in the calcium-sensing receptor. I think two very exciting commercial opportunities, two very exciting opportunities for first-in-class medicines for patients there. I do not think I need to belabor the achondroplasia hypothesis where we feel we have an exciting oral potentially best-in-class option that could provide differential safety, differential efficacy because it targets this well-described condition at its source, driving differential, both changes in growth and also, importantly, impact on parameters that this community cares a great deal about, like proportionality and the like. You know the size of that market from the Voxzogo launch that is ongoing. I think all three very exciting opportunities.
Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)
Thank you.
Operator (participant)
Your next question comes from the line of Biren Amin of Equity Research Healthcare. Please go ahead.
Biren Amin (Managing Director and Senior Research Analyst)
Yeah, hi. Thanks for taking my questions. Congrats on the quarter. Really good launch out of the gate. I guess my question is, what's resonating with healthcare professionals as it relates to the Attruby launch? What are the biggest hurdles that you're seeing for adoption? Maybe a second question, what was the gross to net for the quarter and any impact that you've seen from the Part D redesign?
Neil Kumar (CEO)
Hey, Biren, thanks for the question. I'm going to pass it on to Matt to discuss the HCP piece, and then I'll throw it to Tom to discuss the gross to net piece.
Matt Outten (Chief Commercial Officer)
Yeah, thanks. I guess there's sort of two parts to this. The feedback from the physician segments has been positive, as we've discussed.
Our messaging around, we call it the 34250, but that ability to separate as early as three months and getting results around the hospitalization and the all-cause mortality that we've described, physicians want to see a drug work really fast, and they want to be able to tie it to hard outcomes. Of course, patients do too, but this is what gives people confidence. Those messages have been resonating extremely well. I think that's resulted in physicians trying Attruby, but then also then repeating it, right? Those are the reasons that you sort of try a medication, and then when you see how well people are doing on it, that encourages you to try it again. We have seen a lot of repeat prescribers across a lot of the different segments as well.
I do not think our expectations were otherwise or are going to change anytime soon. We have very strong data package, and we also have very strong programs to help patients get on the medication once that prescription's been written. I'll pass it to Neil to add on that.
Neil Kumar (CEO)
Maybe I'll just elaborate on that for a second before I throw it over to Tom. I think the ever-increasing availability of data, like most recently, Biren, I think we've talked about the variant data, the fact that you could achieve a hazard ratio of 0.41 with statistical significance in that relatively small subpopulation, and as someone mentioned earlier, the sickest of subpopulations continues to reinforce that differential levels of stabilization can lead to ever better outcomes. We're starting to find that that's resonating.
We've got a bevy of serum TTR-associated literature coming out suggesting that ever higher levels of serum TTR correlate with ever lower levels of downstream hospitalization and mortality. The connecting of the dots between ever better stabilization and all of these downstream outcomes, I think, is what's starting to resonate with the physician community on top of what Matt suggested, the backbone, which is the 34250. Tom, you want to talk about GTN?
Thomas Trimarchi (President and CFO)
Yeah, sure. On gross to net specifically, as we've said before, the way to think about this is the floor is going to be the mandatory IRA rebate of 20%. On top of that, you're going to add something like you'd see in other categories where contracting is not really happening. That's what we're seeing here.
I would say, given where we are in the launch early innings, we should expect some variability here quarter to quarter. This quarter, gross to net trended slightly favorable versus what we were expecting. We also saw a slightly lower use of our first-month free program versus what we were expecting. We saw a slightly lower use of our patient assistance program than what we were expecting. These three things together actually converged and caused slightly better net revenue per unit than what we were expecting, but we expect all of this to normalize throughout the course of the year.
Biren Amin (Managing Director and Senior Research Analyst)
Great. Thank you.
Neil Kumar (CEO)
Just to add to that, the results are reflective of strong underlying demand for Attruby and the execution of our commercial team. As Matt mentioned, not a lot of inventory or anything like that.
Biren Amin (Managing Director and Senior Research Analyst)
Thanks. Perfect.
Operator (participant)
Your next question comes from the line of Cory Kasimov of Evercore. Please go ahead.
Cory Kasimov (Senior Managing Director and Fundamental Research Analyst)
Hey, good afternoon, guys. Thanks for taking the question. It is great to see Attruby is off to such an impressive start. You kind of alluded to this in a prior response, but now that you are on the market for over a quarter, how are you thinking about new patient starts for the category going forward? I know previously you have talked about numbers of like 2,000-3,000 new starts per quarter, but that is already looking pretty conservative. Any kind of new color there would be appreciated. Thank you.
Neil Kumar (CEO)
Yeah. Hey, Cory. Thanks for the question. I think you are kind of thinking about it like we are thinking about it. It does seem to keep going up every quarter. If you look historically, that is no different.
I think it is ramping a bit faster, but that also makes sense because you're getting new products in the market. The more companies that launch a product into a space, that creates a higher share of voice. I think that gets people educated either to go get screened or for physicians to think to themselves. I mean, if you're a cardiologist and you have HFpEF patients and you're not thinking to yourself, "Hey, some of these must be ATTR-CM patients," all of these companies out discussing it, educating, talking about it, it gets people looking. If you look, you find it. It's not that uncommon. Most cardiologists have some patients that need to be treated. I think that we don't see that stopping anytime soon. The market could easily be a $20 billion market, and we're not there yet.
There is still a lot of patients who are out there who have not been diagnosed, but I think you're going to see continued high numbers of people being diagnosed now that that interest is just continuing to grow.
Matt Outten (Chief Commercial Officer)
Yeah. Cory, just to add one last thing. A lot of the new diagnosis is coming from the high-volume heart failure clinics that Matt mentioned in his remarks. Obviously, an oral small molecule stabilizer is a great fit for those patients.
Cory Kasimov (Senior Managing Director and Fundamental Research Analyst)
Absolutely. It's very helpful. Thank you.
Operator (participant)
Your next question comes from the line of Greg Harrison of Scotiabank. Please go ahead.
Greg Harrison (Director of Biotechnology)
Hey, good afternoon, guys. Congrats on the huge start to the launch, and thanks for taking our questions.
In our initial modeling conversations with you guys, our takeaway was that your expectation was for initial uptake to come primarily or almost exclusively from newly diagnosed patients. To get to the revenue number you have reported, you have to get most of them by our math. Assuming that is not the case, is this a function of much larger market growth than you expected, or are you getting a large percentage or maybe even most of your patients as tafamidis switches? If that is the case, how do you expect this trend to evolve from here?
Neil Kumar (CEO)
Hey, Greg, thank you so much for the question. I think, as we have said consistently, our focus at launch has been the treatment naive market. Very early on, we got a few more switch patients than we expected, but that started to normalize.
Focus continues to be new treatment naive patients. I think Matt mentioned in his remarks that there we are seeing consistent monthly growth gradually. In terms of what's driving the number, I think it's sort of all of the above, right? I think it's a little bit of the market growth, obviously strong demand and strong conversion. Maybe I'll throw it on to Matt, and he can talk a little bit more about the factors driving conversion and the market size.
Matt Outten (Chief Commercial Officer)
Yeah. No, I think you hit it well, Chinmay. I don't know that I would add that much. It's a little tricky when you try to figure out who a switch patient is. They look like a new patient most of the time. I think it's a little careful trying to determine who's a switch and who's new. Our focus is on the newly diagnosed.
We do see switch patients come in, and sometimes we can tell that they're a switch patient. Other times, it's not clear. I think as you think about the rest of 2025 moving into 2026, I think the market continues to grow. It's been growing double digits now for quite a long time, and this past quarter, one of the best we've seen. I would not expect that to disappear anytime soon. There will be switch patients who want Attruby, and there will be a lot of newly diagnosed patients that want Attruby for all the reasons we've discussed, whether it's the data itself, the programs we offer. I think we're very optimistic about all of that.
Greg Harrison (Director of Biotechnology)
Great. Thanks again.
Operator (participant)
Your next question comes from the line of Paul Choi of Goldman Sachs. Please go ahead.
Paul Choi (Biotechnology Analyst)
Congratulations on knocking it out of the park in your first quarter here on the launch. I want to just shift gears for a minute and maybe just ask a policy question, which is to think about, as Attruby grows in scale over the coming years here or this year and next year, as well as you start to get sales from Europe, from Bayer and Ambianta and AstraZeneca in Japan, could you maybe just help us think through where your IP is domiciled and just sort of the tariff implications and just sort of the royalty streams that you'll be getting from your ex-US partners and just sort of how that ultimately affects your margin and your sort of profitability profile? Any color there or directional guidance would be helpful. Thanks.
Thomas Trimarchi (President and CFO)
Hey, Paul. Thanks for the question. This is Tom. Yeah.
As Neil indicated in his prepared remarks, we're fortunate to have very little impact from any of the tariff discussions that are ongoing. We've done a pretty deep dive on this. As you know, the pharmaceutical has been exempt from the reciprocal tariffs. We've also looked at the IEEPA and what's been said in public around the potential 232 tariffs affecting the industry. When we put all that together, based on our supply chain, we see very, very minor impact. That's because Attruby is made here in the US. We're, of course, an American company, and we have all our IP domiciled here in the US. Overall, very minor impact to the business. I'm not sure I understood the question on the royalties and how that relates, but that's off the top-line revenue number.
Obviously, money coming to us is before any implication on tariffs that would be on their end, but maybe I didn't understand the question.
Paul Choi (Biotechnology Analyst)
No, that makes sense on the ex-U.S. business.
Operator (participant)
Your next question comes from the line of Anupam Rama of JPMorgan. Please go ahead.
Anupam Rama (Managing Director and Senior Equity Analyst)
Hey, guys. Thanks so much for taking the question and congrats on the quarter with Attruby. I wanted to just pop in with a very quick pipeline question. You shared some data today on the chronic hypoparathyroidism indication. What gets you excited about this opportunity, particularly from, you talked about, Neil, from an NPV perspective? How does that all fit in? Thanks so much.
Chinmay Shukla (VP of Strategic Finance)
Hey, Anupam. Thanks for the question.
We're going to drive it to Neil to talk about the NPV, and then Ananth can talk more about the data and our exciting plans for the phase three and HP.
Matt Outten (Chief Commercial Officer)
Yeah. I mean, from an NPV standpoint, Neil, I think you know that this is an exciting extension population, quite a bit larger than ADH1 itself, with actually a pretty reasonable price point as well, given where Ascendis headed up pricing their medicine. There is a variety of different ways for us to take advantage of the opportunity now that many of the oral competitors have fallen by the wayside. I'm going to actually pass it over to Ananth to talk a little bit about the exciting data that we just posted.
Ananth Sridhar (COO)
Hey, Anupam. Great question. Thanks for your interest in this program.
As you mentioned, we reported data from the first nine participants with post-surgical hypoparathyroidism that were treated with Encaleret. Normalized blood and urine calcium concomitantly in seven of these participants and serves to be an important oral option for these patients seeking to resolve calcium homeostasis. We think that this could be a treatment-changing or paradigm-changing treatment, and we will advance development towards registration for this program. In terms of the NPV or the market opportunity, like Neil mentioned, this is about a seven- to eight-times larger marketplace than the ADH1 market alone. It could grow and expand the presence of Encaleret as we continue to investigate the molecule.
Anupam Rama (Managing Director and Senior Equity Analyst)
Thanks so much, guys.
Operator (participant)
Your next question comes from the line of Ellie Merle of UBS. Please go ahead.
Ellie Merle (Executive Director of Biotech Equity Research)
Hey, guys. Thanks for taking the question and congrats on the quarter.
Just curious what you're seeing so far in terms of commercial trends since Attruby's approval. You have a few weeks of experience now with this so far. I mean, I guess specifically, was the rate of new unique patient prescriptions consistent with what you saw in February and March? Did you see an increase by April just associated with a broader prescriber base? Have you maybe seen a dip in the rate of new unique patient starts just with the launch of a competitor? Any sort of high-level commentary on how you're thinking about positioning? Are there certain segments where you see potential greater uptake or advantages in terms of your use? Thanks.
Matt Outten (Chief Commercial Officer)
Sure. This is Matt. Thank you. The second half of your question, the audio was a little garbled.
Let me answer the first one, and then if you want to repeat the second one, I'm happy to address that as well. Your first one regarding Amvuttra. There is definitely a place for lots of choices in this market. I think as a company, we are obviously happy when patients have additional choices. In terms of where Amvuttra is going to be placed, they seem to be earmarked for mixed phenotype at the moment. That is probably 10% of the overall market. Their variant data was not stat-sig, and they are very expensive. It is twice as expensive as Attruby right now. They have to compete, obviously, with our 340, 250, which has been pretty successful. I do not know where that is going to land for them. I think they have to figure out their pricing. If you are going to charge double, you need to have better results.
I think you can ask them to talk about that. I'm sure they'll have opinions on that. Right now, it's early, but we're not seeing a lot of uptake outside of the mixed phenotype.
Ellie Merle (Executive Director of Biotech Equity Research)
Got it. Maybe this was the part of the question that broke off. Let me know if you can't hear me. Just in terms of the rate of unique patient prescriptions, I guess, have you seen any change in that since the approval of Attruby? For instance, if you saw a dip in the rate of new unique patient prescriptions in April, or if, say, now that you have a broader prescriber base, you've seen a similar rate in new patient prescriptions or even higher?Thanks.
Matt Outten (Chief Commercial Officer)
Yeah. The April data, I probably wouldn't be able to comment on.
I mean, they were sort of out two weeks in Q1, and now we've picked up some data. We see some of the same stuff that you guys see. The trouble is it's buy and bill. They're trying to convince a community physician to put out over $100,000 per injection. The vitamin A part's cheap. From a cost perspective, that's fine. You still have to take that every day. That out-of-pocket for the doctor, they have to cash flow that. They have to put that money out, and then they have to wait to get reimbursed. If you start stacking up a lot of patients, that's a lot of money, and it gets pretty expensive. We haven't seen it yet. It doesn't necessarily mean it is or isn't happening. I think you'd have to ask them.
Maybe they can do what we did and throw out some early numbers on what the first month of launch looks like.
Ellie Merle (Executive Director of Biotech Equity Research)
Got it. Thanks.
Operator (participant)
No, thank you. Appreciate your questions. Neil, Anupam, Chinmay, comes from the line of Jason Szymanski of Bank of America. Please go ahead.
Great. Good afternoon. Congratulations on the quarter, and thanks for taking our questions. I wanted to return to the question of segment growth for Attruby, if I may. It sounds like you expect the contribution from switches to slow at some point. What does that look like over the near term? I mean, do you have a sense of how quickly you may be going through a bolus of, I do not know, refractory patients versus those, as you mentioned, are looking for a stronger stabilizer because they believe in the better outcomes over time?
Neil Kumar (CEO)
Hey, Jason, thanks for the question.
I think that high level, I can say a couple of things, and then Matt's going to add more details. As we've said all along, we're not seeing any bolus or anything like that. I do think that the focus of our launch is treatment naive, and there we're seeing consistent monthly share growth, and we expect that to continue. We had a 100% share in the switch population, and obviously, that's going to evolve now that there's a competitor. That's sort of how we're thinking about it. Obviously, it's very early to say, and we look forward to seeing how the next quarter goes.
Matt Outten (Chief Commercial Officer)
Yeah. I'll just add, I mean, I agree. We didn't see a bolus. I mentioned earlier, it's a little tricky to absolutely know if someone is a switch or a newly diagnosed.
We do not spend a lot of time sort of thinking about it from that perspective. If patients want to get Attruby, we try to make sure they can get it for whoever they are, newly diagnosed or switch. In terms of what that looks like over time, I think that is hard to predict. You can take the number of patients on tafamidis. You can add on a progression rate of whatever you think is correct and then kind of model that out over time. I think that is probably the best approach of any.
Operator (participant)
There are no further questions at this time, and that concludes our Q&A for today. I will now hand the call back over to the company. Please go ahead.
Neil Kumar (CEO)
Thanks, everyone, for your questions today. We appreciate your interest in BridgeBio and look forward to updating you again next quarter.