Hello, welcome to this fireside chat with BioMarin Pharmaceutical Inc. I'm Joe Schwartz, Senior Equity Research Analyst at SVB Securities. It's my pleasure to be joined by management, including J.J. Bienaime, Jeff Ajer, and Brian Mueller. Thank you so much for joining us today. Maybe we can start by having you, J.J., give us a quick rundown of the company's key initiatives and catalysts that we should look forward to over the balance of this year, and then we'll go to Q&A.
Sounds good. Thank you, Joe, and good morning, everyone. Thank you for joining us today. As you know, we are less than two weeks away from our Q4 full year financial results call, so we would like to avoid specifics of the fourth quarter. In January, we provided a high-level strategy and framework for growth of the company in the near term and by mid-decade and throughout the end of the decade. With the core components of growth in place, including our steady growing base enzyme business, our two recently approved larger opportunities with VOXZOGO and ROCTAVIAN in initial indications and beyond under a lifecycle management plan, and our proven early-stage development capabilities, our plans to deliver sustainable growth and value creations are in place.
I would say that our track records having developed, you know, eight best-in-class and first-in-class genetic medicines and created markets where significant unmet needs existed, including achondroplasia, phenylketonuria, numerous enzyme replacement therapies, and the world's first approved gene therapy for the treatment of severe hemophilia A. I would say this track record is unmatched by for a company our size in the industry. I would say these product successes have brought BioMarin to a momentous inflection points where we have transitioned to a growth and profitability story. VOXZOGO, the only approved treatment for children with achondroplasia, is a prime example of the kind of opportunities that we will pursue on a going forward basis.
We increased guidance on VOXZOGO 4x last year, based on the tremendous unmet need for a medicine to treat the underlying cause of achondroplasia. I would say that ROCTAVIAN gene therapy for the treatment of severe hemophilia A is a truly disruptive therapeutic option for people who currently have to rely on chronic medicines with injections every week or twice a week. We remain true to our roots now with the benefit of over 20 years of drug development experience. We have a global infrastructure that's unmatched for a company our size. We have a durable and growing base business that has enabled the successful pivots to the development of medicines for larger genetic conditions and that leverage our fully integrated and scaled biopharmaceutical capabilities.
Our early-stage pipeline is now the richest in BioMarin's history, and we look forward to showcasing those assets at R&D Day in September in New York. There is so much more to share, but the key takeaways is that our core business, our core capabilities, including drug discovery, clinical trial executions, global regulatory expertise, reimbursement, commercial and worldwide manufacturing, have positioned BioMarin to drive growth and value creation for the foreseeable future. It's a very exciting time for the company. I will turn it back to you, Joe, for questions.
Great. Thanks, J.J. First, to follow on to what you were saying about the financial performance and guidance that you communicated recently, I noticed you reported preliminary total fiscal year 22 sales of $2.09 billion in VOXZOGO, fiscal 22 preliminary sales of $169 million in January. You didn't provide fiscal 23 guidance like you did last year. Is there a reason why you didn't provide forward guidance for VOXZOGO?
We, we wanted to signal the significant momentum and uptake that continues through the end of 2022. We did in fact state that we are basically at the end of, as of December of last year, we were on a run rate of $300 million a year. There is no specific reason why we didn't provide 2023 guidance, except that we wanna provide a more specific and as up-to-date-as-possible 2023 outlook on our upcoming Q4 call in a few days.
Yeah. Okay.
Things are doing very well. VOXZOGO is beating our own expectations and it's going to be a very large product, the largest product that we have launched so far. We'll see. It's going to be neck and neck with ROCTAVIAN, hopefully.
Yeah. That leads in well to my next question actually. Can you talk about what metrics, segments of that market were initially underappreciated but became a stronger driving factor than you expected last year, and to the forward guidance increases as a result?
Yeah. I will let Jeff Ajer, our Chief Commercial Officer, answer that question. Maybe I'll add a few things when, after he's done. Jeff?
Thanks, Joe, for the question and acknowledging the strength of that launch. I'd say there isn't a single factor that we misjudged. If you look at our history of launching drugs around the world, we drew a lot from that base of experience up to and including how long it takes to get reimbursement started in different markets, the pace of patient identification and then leading those patients on the therapy. I would say in general, those processes were moving faster for VOXZOGO than they had for the previous brands in our portfolio, kind of across the board. It wasn't one thing.
It was, you know, the speed of getting into named patient sales markets, the speed of being able to get through, reimbursement in key European markets that allowed us to start treating, material numbers of patients. What I think that does is it underscores what J.J. said, the high unmet need that is recognized for treatment of kids with achondroplasia and the powerful clinical data package that we had behind the approval of VOXZOGO that really demonstrated the value proposition. The one other thing that I would call out is that we got a launch in Japan in August of last year. Approval in June, reimbursement approval in August, and subsequent launch. We've long operated in Japan with our enzyme replacement therapies.
They've been a small part of our business, we invested in Japan to be able to, you know, have the infrastructure and team ready to go when we had the right product in Japan. I think what we've discovered, the one upside surprise we've discovered that's worth calling out is VOXZOGO really is the right product for Japan. Epidemiology of achondroplasia in Japan is higher than it is for the enzyme replacement therapies. The value proposition really resonated in Japan. Probably we got substantially faster uptake in Japan than we were expecting, and that was the one specific surprise, happily.
Yeah. Very helpful.
It's also because, again, we have a well, you know, oiled infrastructure and experience, you know, in launching rare disease drugs around the world. It's starting to show. Also the fact that as compared to enzymes, you know, our previous products launches, the challenge was to find the patients. Here the patients are generally, you know, pretty well diagnosed, are diagnosed before birth, most of them. Which also is helping. The fact that the product is very effective.
Yeah. Right. Okay. Thank you. Can you talk about the status of your label expansion strategy in younger children under five in the US and two in Europe?
Yeah. I mean, we were very pleased to share in early January that the EMA had validated our application so for extension of VOXZOGO label to children under the age of two. As you know, in Europe, the product approves from three years of age and up. In the U.S. it's five years of age. We expect, you know, we expect actions from both the U.S. and the European authorities in the second half of this year. As you know, in Japan, VOXZOGO has no age restriction today.
Yeah. Considering we only saw trends in improvement to growth velocity in younger children, how confident are you that we can get a label expansion there? And if you're able to do that, you know, there was a competitor that, you know, had some data that was confounded by, you know, the mix of younger children in their study. Does that imply that, you know, they may be able to, you know, handle the challenges in younger children as well?
I mean, our confidence is based on the belief that starting treatment as early as possible is necessary to see the most benefit. We are hopeful that, you know, younger children will have the opportunity to access VOXZOGO. In Japan, again, the product is approved for all ages. We treated a baby as young, I think as three weeks of age. Then so far in Japan, the safety profile has been good and has been also in our clinical trials for patients under five. So it would be beneficial to patients if the age range in the EU and the U.S. was broad.
Also, we understand that, you know, for products in general, the requirements from regulatory authorities for age expansions are not as stringent as they are, you know, for new indications, for instance. It's mainly related to safety, and we believe that we have a pretty good safety profile in patients under five there.
Yeah. Okay. That makes sense. Maybe switching gears to ROCTAVIAN. To your knowledge, is there anything in particular that the FDA wanted to see with the three year phase III data look?
Not, I mean, they haven't told us that. I mean, we kind of, you know, we were not surprised when they asked for it because we knew that, you know, when we filed in late September of last year, when we refiled, that this data would be available during their review process, which is a six month review process. So we assume that they would be interested, given the fact that this data would be available before they have to make a final decision. But they haven't, you know, told us or given us any information as to what exactly they're looking in the data. I mean, to me, it's probably more related to the durability of effect beyond year two and having three years of data, you know, is definitely valuable here.
You saw the results we presented at a investors conference in early January. We are very pleased with those results.
Yep. Yeah. When would you expect to know whether the FDA considers that data at three years a major amendment, given the PDUFA's next month? You know, a lot of folks are wondering, is there any precedent for this sort of a situation or regulation that, you know, stipulates when they will give an announcement? Could it be as late as the PDUFA, or would you expect it to if it was going to be considered.
Yeah.
-a major amendment, would you expect it to happen sooner than that?
I mean, there is no specific regulations. I mean, generally, they do tell you within a month or so of your filing, but they actually can issue a major amendment up to the PDUFA action date. But so far, they haven't told us that the data we submitted is a major amendment.
Yep. Okay. Turning to your study 270-303 prophy steroid regimen data that'll become available in early this year. Any updates to that?
No, I think we'll have the top-line data in Q2.
What's Q two now?
Sorry?
two, 2Q now.
Yeah. Second quarter. I mean, early second quarter. There is no requests from the FDA to review this data at this time. There hasn't been any in all our discussion with them. We are in very active discussion with the FDA right now on the filing. We don't, you know, we don't believe that the FDA decision is related or dependent upon this, the 303 study. Remember that at year three, the phase III ROCTAVIAN study met all primary and secondary endpoints with 92% of patients off prophylaxis at year three. We are, you know, we were very encouraged with the consistent clinical response at this time point and believe it is again supportive of the transformative potential of ROCTAVIAN.
We have no reason today to believe that the steroid, the 303 steroid study data is needed for approval. It was not in the EU, by the way. We got approved in the EU without the data.
Yeah. I guess why is 303 study designed the way it is? Can you talk a little bit about, you know, what it will tell you and practitioners for the best way to use ROCTAVIAN?
Yeah.
with steroids?
I think the genesis and the history of it is the fact that, as you know, we had slightly different results in the phase III study as compared to the phase II study. Where in the high-dose regimen we had, you know, prophylactic steroids as opposed to in the phase III we had on-demand steroids. The hypothesis is that we're trying to read is chronic steroid better than on-demand steroid. Okay? That is what the study is supposed to answer, and this is why we implemented that study. I would say, again, we have, as I just mentioned, very good data with the on-demand steroid that was used in the phase III trial.
now if we can do even better by with using prophy steroid, why not? That's why we gotta, you know, we trying to get an answer to that question. If indeed, that study, the 303 study does show that prophy steroid is better than on-demand steroid, we could post-approval, you know, amend the guidelines for steroid usage, you know, with ROCTAVIAN, after approval.
Yeah. Okay.
Mm-hmm.
That makes sense.
Mm-hmm.
In terms of the launch, in January, you said that you feel confident about street estimates, assuming ROCTAVIAN is approved in March. However, it's uncertain if it might get delayed. When you provide guidance, very soon, you know, how should we expect to see that structured or communicated when you announce it? Will you include European and U.S. sales, or just Europe separately, you know, and then say plus or minus the U.S.? How are you thinking about...
Yeah.
-that?
It's a great question, Joe. We know it's on everyone's minds. I'll jump in there and just again, given we're a week and a half away from the call, I'll just ask you to stay tuned for Monday, the 27th, and we'll look forward to talking about ROCTAVIAN in 2023 then.
Okay.
We will provide the only thing I can say, we will provide ROCTAVIAN guidance on the call, you know, on the 27th.
Great. Thank you. Understood. Jeff, can we talk about the eligible market, pool of patients? Given the eligibility criteria, you need to be AAV5 negative, have no liver impairment, no inhibitors, et cetera. And in Europe, you said there's like 3,200 patients or so that could be eligible. What is the eligible market in the U.S., and is there like a one of these factors that is more significant than the others in terms of limiting it? Can you help us envision what it looks like in the U.S.?
Definitely. Thanks for the question, Joe. Just a point to note, when we talk about eligibility, that's at what we expect in the U.S. and what we know is the initial label indication in each of U.S. and Europe. We will be working, we have studies ongoing right now to try to open up that patient funnel through lifecycle management initiatives over time. As you stated, our previous estimate for Europe was 3,200 patients in the EMA markets that would be eligible with the label indication that we received, and approaching 3,000 in the United States is our expectation. When you look at the funnel, you noted the different cuts for eligibility, but I'll just start kind of at the top of the funnel.
The approvals are for adults. If you do an age cut of 18 years and older, that gives you 60% of the population, you know, that remains eligible as adults. 40% that are off the table as pediatric patients, and off the table for now, because we'll be studying ROCTAVIAN in adolescent patients over time. The second big cut is the severity cut. The numbers are variable by market, and even sometimes the numbers are variable over years when you look at the registries and the published data by the patient associations. Overall, about 50% of hemophilia patients are categorized as severe and would be eligible for ROCTAVIAN at launch, and 50% are something less than severe and are thus outside of the initial label indication. Those are the big cuts.
AAV5, sero negativity, we've done, we've done work on that that's been published. That varies by country. Overall, you could say if you mix across Europe and the United States, you might say about 35% or about a third of patients you would expect to be seropositive for AAV5 and thus not eligible for the initial label indication. Those are the big ones.
Okay. Very helpful. A question that we always get is, you know, who is the prototypical patient that's going to wanna reach for this first? You know, this is a very informed patient community. Are you seeing any patterns according to, you know, the folks that have gone through screening in Germany, for example? Is there any common demographic thread throughout this, or is it really just evenly distributed across age and other demographic features?
Well, in Europe, and this is important, data privacy regulations preclude us from having that kind of information about the patients that are going through the process to be treated. We don't have the window that we might have had some years ago with our, with our enzyme business. However, we've done a lot of market research to try to home in on, you know, what is, what is a likely profile for early adoption? Is there, for example, a niche profile that ROCTAVIAN would fit over time that we need to be aware of, or is that broader? This is really important. The market research has indicated that in fact, patients across a broad spectrum of age, other phenotypical information, what product they're currently using to manage their hemophilia.
Patients across the spectrum are eligible and interested in ROCTAVIAN treatment. What we think are early adopter profiles could be factor replacement therapy patients that are not performing very well on their current factor replacement therapy. Importantly, the market research tells us that those patients that have not yet gone to Hemlibra are likely to go straight to ROCTAVIAN and not step through a trial of Hemlibra. Super important. Even Hemlibra patients that tend to be more satisfied with their therapy than the Factor VIII replacement therapy patients, this is a group of patients that has demonstrated a willingness to switch therapy in pursuit of better outcomes.
The Hemlibra patients, again, they're more satisfied in general than Factor VIII patients, but we think there's a portion of those patients that would be willing to further switch to ROCTAVIAN in pursuit of additional favorable outcomes. Really broad, and that's really positive for ROCTAVIAN.
Okay, super helpful. Thanks. Jeff, staying with you for a moment and switching to a discussion on the sites. This is often called a one and done therapy, but I think there's a lot of monitoring and a lot of visits and things which may be considered cumbersome. At least in the initial onboarding, tests and the like. Where are you in the communication and collaboration process with the sites who are going to administer the therapy in the United States? How many sites do you expect that, you know, will be available to administer ROCTAVIAN at launch?
Well, first, so, in the United States, there's, you know, roughly 150 hemophilia treatment centers that are actively treating patients. That's a manageable group for us and the scope of our commercial and medical team to get to over time. We're not focusing on getting to all 150 of those right away. We have identified a subset of those hemophilia treatment centers that include, for example, our clinical trial sites in the United States. We've identified the largest, you know, call them comprehensive care centers, if you like, that we're focusing on initially at launch. You're right, there's while this is not a chronic therapy, there is an element of patient readiness and selection and patient monitoring following administration.
Which by the way is most regular in the first six months following treatment, and then it, that monitoring tails off over time after six months. We're targeting, you know, what we think are the biggest and the largest treatment centers in the United States. We aim to have those ready to treat at or shortly after launch, and then we'll be hitting a second wave of those with readiness. We've really honed our technique starting in Germany, where we're ahead of the game, obviously with an approval last year, and we've been really diligently working on the site readiness.
Mm-hmm.
It's a comprehensive effort, and we think we've got a method going here.
Yeah. That's helpful. Do the sites in the United States feel like they're adequately resourced and reimbursed to do all this work?
Yeah, the administration of ROCTAVIAN is not particularly complex. It's an outpatient administration procedure, maybe not so unlike outpatient administration of our enzyme replacement therapies, with the caveat that it's only done once. The actual administration is not really the issue. As for reimbursement, you know, in United States for payer reimbursement, it's a very diverse payer system in the U.S. We've demonstrated with our high value-added therapies, an ability to get reimbursement approvals pretty quickly following launch. That's our expectation for ROCTAVIAN. You know, hemophilia treatment centers derive a benefit from products that they dispense. We think that would include ROCTAVIAN administration through.
Yeah.
The 340B discount, which could be significant on a, at a highly priced product like we expect ROCTAVIAN will be.
Yeah. Yeah.
Just to reinforce what Jeff said, I mean, you know, the administration of our drug is pretty simple. I mean, this is not cell therapy. There is no preconditioning regimen.
Right. I was thinking more-
There is no cell, there is no cell treatment. It's not ex vivo. This is a three-hour IV infusion. That's it.
Follow-up tests and visits.
Oh, yeah. There's some monitoring in the first six months as Jeff outlined, but very simple to administer.
Oh, okay. Can we touch on your pipeline real quick? What are you most excited about? Two-part question. When's the next update on the HAE gene therapy?
Okay. I mean, we share some data also again in early January on different things, including BMN-255 for kidney disease. We showed that BMN-257, which is a small molecule GO- inhibitor, demonstrated apparently a superior efficacy profile as compared to approved therapy for hyperoxaluria in a phase I/II trial. We are continuing to dose patients in our with BMN-331 for HAE. We should have some updates on all of those at the R&D Day in September. Also, we will be providing some updates on our activities in expanding vosoritide's indications beyond achondroplasia also probably by mid-year. Also I'm very excited about BMN-351 for Duchenne muscular dystrophy.
We believe that we have a very pretty good chance based on clinical pre-clinical data to achieve, you know, dystrophin expressions in a 20%-30% range. Not micro-dystrophin. Dystrophin that's very close to the real dystrophin. And we anticipate being treating our first patients in the second quarter of this year with BMN 351 for DMD.
Excellent. Thank you so much for the update, especially at such a busy time. We look forward to following all the continued progress.
Okay. Thanks for having us.
Thank you.