All right. Welcome to the second day of the B of A Healthcare Conference. My name is Geoff Meacham. I'm a Senior BioPharma Analyst, and we're thrilled today to have BioMarin on stage. And with me is Brian Mueller, CFO. Brian, welcome.
Thank you, Geoff. Hi, everybody.
So, I'll kick to you just to say a couple of things, like post-quarter, high level, and then we'll get into some questions.
Yeah, appreciate it. Thanks. Hi, everyone. Thanks again for having us. Great to participate in the conference. We at BioMarin are pleased to be executing on our strategy here in the early parts of 2023, which includes leveraging our profitable and growing base business of mostly enzyme-based products with close to $2 billion in revenue, launching, or hopefully close to launching, two potential blockbuster products in Voxzogo and Roctavian. I'm sure we'll talk more about those. And then continuing to develop and progress our early-stage pipeline of innovative research assets. We recently reported record revenues for the first quarter of 2023 of almost $600 million. That's 15% growth over the prior year, as well as $51 million of GAAP net income. Last year was a key element of our transformation over the last year, a transition to sustainable GAAP profitability.
So we're happy to be delivering on that early in 2023. Voxzogo was a huge contributor to that growth. We raised our guidance to a level of 140% growth over last year at the midpoint of the revised guidance. A large source of that growth has been Voxzogo revenue in Japan, where we've experienced rapid uptake. Voxzogo is approved for Japan for children of any age, which has been a key contributor to that uptake. And I bring that up because we are under review in both the U.S. and Europe to potentially expand the label for Voxzogo to younger children. In Europe, Voxzogo is approved for children over the age of two and in the U.S. over the age of five today. So those potential label expansions could significantly increase the number of patients eligible for Voxzogo.
Briefly on Roctavian, we continue to observe increasing interest from physicians and patients in Europe. We continue to navigate the complicated reimbursement process there. We recently announced a pivot in our strategy to move from bespoke outcomes-based agreements to working with the federal payer on our final German price, which we think will give more broad access to all of the market there in Germany for Roctavian. Likewise, we continue to progress the market access pricing and reimbursement efforts in France and Italy in Europe. We expect those processes to be complete by the end of the year. And lastly, in the U.S., we're approaching our PDUFA date for the U.S. target action date on our Roctavian BLA submission. That's June 30th of this year. So we are looking forward to that potential milestone and poised for potential launch should the product be approved.
So those are some of the highlights. And then we've got some questions.
Perfect.
I'll turn it back to you.
Perfect. Well, let's start where you finished the US Roctavian sort of review process. I know there's some limitations on what you can say, but maybe just at a high level, Brian, walk us through the cadence going back to earlier this year when you had the three-year data. How do you think about that in the context of the product profile and what was really new information that kind of prompted the PDUFA push?
Yeah, of course. Thanks. So yeah, first of all, being just a few weeks away from the PDUFA action date, we're trying to avoid talking about all of the play-by-play in the review over these last few weeks. What Hank shared on our Q1 call a couple of weeks ago was that the activities and the process aspects of the process that you'd expect to be happening are happening and the review continues. But to your question about the change in the PDUFA date and the data, first of all, when you go back to the first BLA review back in 2020, while we had filed for accelerated approval, we recognized that back then, compared to now, was a really limited set of data.
We had an interim cut on a small subset of patients in the phase III study after just a few months, and then a limited amount of data on a small phase II study with seven patients or so. Here in this BLA submission, we already had two years of data from our 134-patient phase III study that was in the original or in this resubmission of the BLA last fall. And because durability has been one of the questions about gene therapy in severe hemophilia A, knowing that the third year of data from our phase III study was going to become available to us and for the agency to review during this review cycle, the data was announced back in January. It was reasonable that the FDA would want to see that data during the review cycle.
And because it was during an existing review, again, a pretty high volume of data, 134 patients, when we shared with them after packaging the data in the format that they would want to see it, it was not a surprise. And the FDA issued a major amendment, which extended the PDUFA date by three months. But their messaging to us was consistent with what we'd expected, that it was because of that volume of data.
Gotcha. Okay. That's helpful. And just on the U.S., kind of the pre-commercial activities, you guys have launched a ton of orphan indications drugs. What's different about this? How can you make some of those conversations happen with providers, payers, etc.? What can you do in advance? And what is sort of left to do, obviously, beyond the formal approval?
Yeah, thanks. Great question, Geoff. Appreciate it. So of note there is, while the delay in Roctavian's ultimate review and FDA decision here over the last couple of years was unfortunate and took a lot of extra time, two things that come to mind and that could be positive for the Roctavian launch are, number one, the significant volume of additional data, both safety and efficacy, that we've generated over the last couple of years that I mentioned that drove the current filing and PDUFA date change. But that data, if you could picture that being packaged and shared with payers, as well as, again, after approval, the patient community, given Roctavian's consistent durability and safety profile, should be helpful for the launch. Then on the payer side, likewise, again, while the delay has been unfortunate, we've been able to make the most of this additional time we've had.
There are some safe harbor regulations in the U.S. that permit manufacturers to engage with payers before an actual approval. So that's been an active part of our pre-launch activities. Because the existing standard of care, whether it be prophylactic Factor VIII or Hemlibra, is very expensive to the U.S. healthcare system today. And many of these payers in the U.S. are keenly aware of how expensive their severe hemophilia A patients are to their system. And as we saw in our own study, are still experiencing bleeding rates or a certain level of bleeding rates on the standard of care. So that's a pretty big motivator, we believe, for these payers to engage with BioMarin on Roctavian, which has the potential to offer years of freedom from their standard of care and better bleeding control, as we've seen in the phase III study.
So we've been engaged in those discussions. We've been doing our best to understand the landscape of the payer mechanics in the U.S. We've had several large payers in the U.S. approach us for that same reason I just mentioned. So it's been a key part of the efforts. And as you noted, Geoff , we need to wait for the actual approval itself, but we are ready to go.
Gotcha. And then last question on the U.S. With respect to patient sort of inquiries and physician inquiries, how is that kind of, what's the cadence of that over the course of this year?
In the U.S.?
Yeah.
Yeah. So limited availability or limited ability, of course, in the U.S. to engage with patients before an approval. We did share previously that we did offer some mechanisms for severe hemophilia A patients interested to learn about gene therapy to opt into a program. We shared that approximately 300 patients, not just people looking for information, but actual severe hemophilia A patients had explored that information. So that was a good signal of interest. Again, we're engaging with the patient communities as well, patient associations. That's a very robust network in the severe hemophilia A space. And likewise with physicians. We've had a number of U.S. physicians that have been part of our clinical studies. They've had patients that have done very well in the studies.
So we think that they understand Roctavian and what it has to offer and will also be a big key part of the hope to launch.
Perfect. Okay. In Europe, let's talk a little bit about kind of the initial strategy. But one of the things I want to ask you, though, first, is going into the negotiation with Germany and across Europe, I guess you guys, you have a standard of care already, and so you're talking about a benefit as an alternative. And I think that's the way payers were thinking about it. It's not like there are no options, right? So why the timeframe to sort of negotiate in Germany, I guess the question is, what was initially, I think you guys were pretty bullish on getting this done, given your experience last fall. What would you say is the couple of things that ultimately prompted delay, delay, delay, more red tape?
Yeah. Thanks for the question. So first, as you know, and this is different from other BioMarin launches where in our ultra-orphan disease past, we were launching products that had no prior approved therapies. So in those instances, you could envision how payer engagement when there's no therapy versus a standard of care like there is in severe hemophilia A to be different. So we did recognize we were launching into an area where there's an existing standard of care. However, we again have seen in our clinical studies that Roctavian has the opportunity to both reduce bleed rates as well as reduce the number of infusions on that standard of care and have a chance to actually return value to the system over time. So we feel like the value proposition for Roctavian is still there.
And hence the plan to engage during the usual longer pricing and reimbursement negotiation periods for when there is a standard of care, which, by the way, can typically take a year or more in Europe. And so the fact that it ends up for Roctavian that it is taking us longer than we expected, it's not very different from other product launches where there is a standard of care. And so the strategy initially, knowing that we would ultimately engage with the single national payer in Germany, GKV, our strategy was to engage with the statutory health insurers or sub-insurers and provide access to Roctavian through unique individually negotiated arrangements that would include both price as well as an outcomes-based agreement.
When we say outcomes-based agreement, part of the value of Roctavian, which is a single infusion of gene transfer therapy, but has the potential to deliver effectiveness over a number of years, and if that's the value proposition, if patients are not using their prior standard of care for a longer period of time, at a minimum, that cost offset, if that's recognized in the upfront single price for that single infusion of Roctavian, it's important to be able to stand behind as the manufacturer and provider of Roctavian that value proposition.
We plan to do that through these outcomes-based agreements, which basically would say that if the patient were to experience their Roctavian to stop being effective to where they had to resume their prior standard of care, that BioMarin would take on the financial obligation and basically reimburse a sort of proportional value of that upfront Roctavian price that that particular payer never realized. So while we engaged with these sub-insurers in Germany in good faith and had made lots of progress and had been close to executing several of these agreements and in fact have executed a couple, it just became clear over time that this is very novel. These are material complicated agreements.
And that being the primary strategy, especially now that we're getting closer to actually negotiating and finalizing a price with a single national payer in Germany by this September, it became clear that that was the better long-term strategy to enable access to this market rather than these bespoke outcomes-based agreements. But it did take us several months. And again, we were making progress along the way. We did prove out the concept by executing a couple of these arrangements, which remain active and have the opportunity to treat patients up until the point where we have a final price. There's also a mechanism for patients in Germany to get individual access through a named patient sort of exception approval process until we have that final price. We're now outside of the free pricing window in Germany.
That was also a factor along the way in the early months of these negotiations. The free pricing period in Germany used to be 12 months, whereby there was no clawback mechanism if the final price ended up being lower than a price that a launch product was selling within the first year. In January of this year, that free pricing period in Germany changed to six months, and so for Roctavian, that was March 15th, so after March 15th, whatever the final price is in Germany, any payers will be protected, so through these couple of mechanisms, whether it be the OBAs in place or named patient sales, based on the patient interest we've seen, their patients are beginning the diagnostic testing and are interested in treatment. We believe physicians are interested in treatment.
So we think it's this pool of patients that should provide our first commercial patients here in the near future.
So are the newer agreements, the newer strategy, when you have those agreements in place, ultimately, is there an outcomes element to those?
Great question. So one of the things we realized that through the complexity of negotiating these outcomes-based agreements, and we remain open to these types of arrangements in Germany, globally, in the U.S., we can get into this. We plan to have a similar value protection for payers through more of a warranty arrangement. But in the more recent discussions, in our initial meetings with the German authorities, we also realized that there's a strategy where we may not require these complicated outcomes-based agreements, which, of course, are going to have a logistics tracking mechanism that lives on to the future. Because we do have a wealth of clinical data, again, I've mentioned the 134 patients in the phase III study. Our patients in the phase II study have now been through six years on Roctavian.
You can get comfortable what the long-term durability models and therefore the financial value of Roctavian may be. And you may be able to get to a place in a price negotiation where you can quantify that value of any folks that don't realize the full value of their Roctavian because they resume their standard of care, which is less than 10% in our phase III study, by the way. You can quantify that and actually work it into a price negotiation without the presence of an actual OBA. So that remains a possible part of the strategy.
Okay. That's perfect. And then you guys had mentioned the number of patients in Germany that have gone through the diagnostic path and all. Do you have an update on that?
Yeah. So we announced a couple of weeks ago that there were 18 patients that had begun the diagnostic testing first for the lack of presence of antibodies to the AAV5 vector. And then there's a healthy liver testing and other counseling as well. So we're seeing that number increase. We haven't updated that number yet, but we are seeing continued folks raise their hand.
And then, when you look outside of Germany, you mentioned you have the rest of the big five that this fall will be the one-year kind of anniversary. Is there any thought that you could maybe go earlier across Europe outside of Germany?
The named patient sales route remains available for any motivated physician that can navigate that process and get an individual access. I have heard of those. But generally speaking, and it's mostly France and Italy that we're deep into the process, we'd expect that to take a year or a little more, which is why we're expecting that by the end of the year. But we mentioned recently that we are seeing prescriptions and some patients begin the diagnostic testing in other countries globally. Likewise, certain countries in Latin America like Argentina or Middle East like Saudi Arabia, these would be named patient sales. Many of these countries have approval and/or reimbursement processes that take even longer than Europe. But named patient sales routes would be available there as well. So we would hope to see some patients outside of Europe as well.
And then, final question. When you think about a lot of the unforeseen kind of challenges on the discussions in Europe, do you think that ultimately could have some predictability to the discussions you're going to have in the U.S.? Or is that just a completely different process?
It's a great question, especially given the challenges that we've had and haven't had the commercial patient ramp in Europe that we had hoped at the beginning of the year. The way I characterize how to think about some of those challenges in translating the U.S. are the key complicated driver has been the negotiation of these outcomes-based agreements. Price and value, of course, as well. But these outcomes-based agreements are novel for this large of an indication, this material of a price level for an individual dose, the long-term nature of the durability, the administration thereof, the translating these negotiations into contracts. That was the key driver that was complicated over the last several months in Germany. And we are not expecting that same level of complication in the U.S.
While we plan to, again, offer that same level of value protection in the U.S., we are planning to do it in the U.S. in the form of a standardized warranty that will be terms and conditions around the performance of Roctavian, defined as that particular patient staying off of their prior standard of care. But should the patient resume their standard of care, and again, in our phase III study, that's been less than 10% of the patients, you could envision a pro rata proportional value reimbursement by BioMarin for that piece of the Roctavian value that was never realized. But if you picture when that happens over a certain period of time, again, calculated in a very fair pro rata fashion, the actual mechanics of that warranty can be documented and issued in a standard way with the purchase of Roctavian and not negotiated payer by payer.
It's been described similar to a car warranty where it's a very important value protection for consumers where you pay a lot of money and invest in a vehicle, and the warranty covers the most expensive parts of the vehicle to perform over a certain period of time. However, you don't negotiate that warranty when you go to the car dealer and purchase your car. You accept it. It comes as standard issue with the vehicle. So I think that's a fair analogy.
Good analogy. That makes sense. Okay. Well, you do have other franchises. So let's talk about Voxzogo. Consistent growth, really, since you launched. I would say maybe the question is, what have you learned since launch about the size of the market and kind of the awareness? Obviously, you guys have raised guidance a bunch and you've beaten numbers pretty consistently.
Yeah. Thanks, Geoff . The number one learning, which again was always part of the promise of Voxzogo during its development cycle, is that patients and patients' families and physicians are willing to treat achondroplasia with Voxzogo. This represents BioMarin's largest market opportunity. As many of you may know, we grew up in the ultra-orphan product business, monogenic disorders, mostly enzyme replacement therapies. These are patient populations, in some cases, a few hundred or single-digit thousands of patients globally. Achondroplasia is significantly larger, still a rare disease, but approximately 18,000 patients in BioMarin's global territories, and I say that because while we've been pleased in observing this rapid uptake of Voxzogo globally, we're now selling in 35 markets.
We raised guidance four times last year and again early in 2023 on our Q1 call a couple of weeks ago, but we are still relatively low in penetrating the global market.
We believe we have approximately 1,500 patients on commercial Voxzogo. So that's still less than 10%. And again, selling in 35 markets, but BioMarin sells our products in over 75 markets. So even within the BioMarin global footprint, we have more territories to launch Voxzogo within. And then deeply penetrating those markets, especially larger markets like the U.S., which are more complicated because of our diverse geography and diverse patient populations. There have been certain countries. Japan is the best example, where, as I mentioned in my opening remarks, there are no age restrictions. And so we've seen Voxzogo uptake in Japan across all ages. We've treated several infants, in some cases just a few weeks after birth. So that level of interest has been motivating. Likewise, the large patient population that's left to penetrate is equally motivating. So it's been a great launch.
Gotcha. Okay, and then can we talk a little bit about the additional indications? I think you guys are running sort of a basket study maybe. Talk about when we could see that data and then what kind of opportunities that could bring.
Yeah. Thanks. So Voxzogo today approved for achondroplasia, monogenic disorder, the most common form of dwarfism. However, the biochemical pathway for achondroplasia in Voxzogo, the CNP pathway, is similar for other genetically defined short statures, and the belief is that Voxzogo can have a benefit in some of these other disorders. The study that Geoff is referring to is an investigator-sponsored study, Dr. Dauber from Children's National Hospital in Washington, D.C. Dr. Dauber started this study a couple of years ago now. Last year at the 2022 Endo Conference, Dr. Dauber published an interim cut of his data. It was some annualized data from six months of treatment for a subset of these patients, again, across a number of disorders, hypochondroplasia, Noonan syndrome, SHOX deficiency, NPR2, and a couple of others. So Dr. Dauber recently has expanded the population in that study.
While we are anticipating, we'll be waiting for another readout from that study. We believe, based on what we've seen in this interim cut, that the effectiveness and the potential of Voxzogo to help some of these disorders is there. We started a strategy last year to start to develop Voxzogo for these additional indications. The current status of those development plans is engaging with regulators to design the right registration pathway. This would be clinical study design, number of patients, endpoints, etc. We're going through that process. We probably won't talk about details until they're more final so we can talk about what actual studies look like and registration pathways look like. Just a reminder for those that have followed the Voxzogo story and achondroplasia, we had started our phase III study.
And after starting the phase III study, the FDA convened an advisory committee meeting about the treatment of achondroplasia with pharmaceuticals. While that AdCom wasn't specific to Voxzogo, ours was the only phase III study going on at the moment. And there was FDA feedback in that AdCom about what a pivotal program should look like in achondroplasia, which was two years of data in two age groups and two studies as well. And we didn't have that in our single phase III. Our strategy with Voxzogo for achondroplasia was to help satisfy the agency's questions with the totality of our data set, which included some long-term phase II study data, as well as a second study we had in younger children, which we've now shared. And all of this resulted in the conditional approval.
It's a long way of saying if we're going to take Voxzogo and try to develop it in additional indications, some of these are very large indications, we want to make sure that we've got good clarity on the development pathway with regulators before we start those programs, and so we'll probably wait to talk about details until we get to that point.
Gotcha. Okay. With that, we're out of time. So thanks a lot, Brian.
Yeah. Thanks, everybody. Thanks, Geoff .