BioMarin Pharmaceutical Inc. (BMRN) Q1 2022 Earnings Call Transcript

BioMarin Pharmaceutical Inc.  (NASDAQ: BMRN) Q1 2022 earnings call dated Apr. 27, 2022

Corporate Participants:

Traci McCarty — Vice President, Investor Relations

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Henry J. Fuchs — President, Worldwide Research & Development

Brian R. Mueller — Executive Vice President, Chief Financial Officer

Analysts:

Salveen Richter — Goldman Sachs — Analyst

Chris Raymond — Piper Sandler — Analyst

Robyn Karnauskas — Truist Securities — Analyst

Cory Kasimov — J.P. Morgan — Analyst

Paul Matteis — Stifel — Analyst

Gena Wang — Barclays — Analyst

Geoff Meacham — Bank of America Merrill Lynch — Analyst

Phil Nadeau — Cowen and Company — Analyst

Matthew Harrison — Morgan Stanley — Analyst

Joseph Schwartz — SVB Leerink — Analyst

Debjit Chattopadhyay — Guggenheim — Analyst

Joel Beatty — Robert W. Baird — Analyst

Luca Issi — RBC Capital Markets — Analyst

Presentation:

Operator

Good day, and thank you for standing by. Welcome to the BioMarin First Quarter 2022 Financial Results Conference Call. Hosting the conference call today from BioMarin is Traci McCarty, Group Vice President of Investor Relations. Please go ahead, Traci.

Traci McCarty — Vice President, Investor Relations

Thank you, Ashley. Thank you everyone for joining us today. To remind you, this non-confidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including expectations regarding BioMarin’s financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin’s product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors and those factors detailed in BioMarin’s filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K report.

On the call today from BioMarin management are J. J. Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President, Chief Commercial Officer; Hank Fuchs, President, Worldwide Research and Development; Greg Guyer, Executive Vice President, Chief Technical Officer; and Brian Mueller, Executive Vice President and Chief Financial Officer. I will now turn the call over to our Chairman and CEO, J. J. Bienaime.

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

Thank you, Traci, and good afternoon, everyone. Thank you for joining us today. So we begin 2022 poised for significant growth and the transition to sustainable GAAP profitability, interest in Voxzogo from family seeking a treatment option that addresses the underlying cause of achondroplasia has been very positive as underscored by today’s increase in full year 2022 Voxzogo guidance to between $100 million and $125 million. We also reaffirm previously released financial guidance for all other metrics included in our full year 2022 guidance.

So, we generated $519 million record revenues in the first quarter, representing 11% growth year-over-year excluding Kuvan. This marks the start of BioMarin’s return to significant double-digit growth. Actually, the revenues for products marketed by BioMarin were up 15% including Kuvan, so really off to strong start to double-digit revenue growth hopefully over the next few years. So this result highlight the strength of our base business and the significant opportunity that lies ahead with Voxzogo. It is important to note that $13 million of the $20 million total for the first quarter for Voxzogo sales were from outside the United States, emphasizing the breadth of our global footprint and commercial capabilities and the importance of the ex-U.S. markets. This will be advantageous as we prepare for the potential European launch of our ROCTAVIAN in the second half of this year ahead of a potential U.S. approval.

With the financial outlook and robust global launch of VOXZOGO tracking to plan, we look forward to embrace to the next important regulatory steps with over the coming months. For people with the hemophilia — seeking hemophilia A, seeking control may superior to just [Indecipherable] trading treatment option based on the results that we’ve observed in our Phase 2 and Phase 3 states. We believe these data provide supportive evidence of efficacy as part of the marketing authorization application currently under review in Europe and plan for inclusion in our BLA plan for re-submission in late June.

We were also pleased to share that news today that we have completed the genomic analysis of the salivary gland mass from the participants in our Phase 2 ROCTAVIAN studies which were treated over five years ago. But findings from the completed analysis did not identify evident that vector integration contributed to the salivary gland mass. This is great news for patients and the safety profile ROCTAVIAN and actually before and to our AAV gene therapy field. Jeff will say a few more words on this in a moment.

As we look forward to the remainder of 2022, we are on our way to achieving the goals set forth at the start of the year. Turning the quarter interest into stable GAAP profitability, ramping up our largest pediatric opportunity to date with VOXZOGO and progressing ROCTAVIAN applications with health authorities in Europe and the United States, also advancing the broadest early stage pipeline in our history. We will continue to build on this financial, commercial and regulatory momentum in 2022 and beyond as we make the transition to an earnings growth story.

So thank you for your continued support and I will now turn the call over to Jeff to discuss the commercial business update. Jeff?

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Thank you, J. J. I’m very pleased with our performance in the first quarter of 2022 recording $519 million in total revenues. The $20 million VOXZOGO contributions in the first quarter drove increased VOXZOGO 2022 full-year guidance to between $100 million and $125 million and will be an important component of our 2022 growth story.

Now, turning to specifics of the VOXZOGO launch, we are pleased to share that as of March 31 this year an estimated 284 children were being treated with commercial VOXZOGO. This includes 201 children in countries outside of the United States and 83 children within the United States. An estimated additional 53 children were in process in the United States as of April 15. At the end of the first quarter VOXZOGO sales were spread across 15 active markets including sales in new markets not previously reported in Saudi Arabia, Slovenia, Czech Republic, United Arab Emirates and Italy. We continue to be very pleased with uptake in the EMEA region, which has been driven by a combination of growth in Germany and collectively from individually smaller markets. Upcoming and outside of these two, we expect potential approvals in Japan and Australia later in the year. The opportunity in Japan is expected to be significant and we expect revenue contributions to begin there later this year.

Turning to launch dynamics in the United States, we have seen prescription demand pick up quickly. We have been able to rapidly convert patient referrals to patient starts. In the quarter, we experienced prescriptions from geneticists and pediatric endocrinologists as expected. We also see more payer coverage policies published, which are largely consistent with our label or our clinical trials criteria and are aligned with our expectations. In summary, we’re very pleased with the pace of uptake during this ramp year for VOXZOGO. Launching in the EMEA regions ahead of the United States was a first for BioMarin and underscore the ability of our experience commercial teams to tap into the large market opportunities regardless of location. This is of particular importance as we look toward a potential ROCTAVIAN launch in the coming months should the CHMP opinion and European decision be supportive.

Turning now to our enzyme replacement therapy brands, Vimizim and Naglazyme both achieved record quarterly results in Q1 of 2022. Consistent with our experience last year for both brands, we fulfill large orders during the first quarter from such markets as Turkey, Brazil, Egypt, Russia and Saudi Arabia. This demand is gratifying and good for our business and we expect will cause the first half of 2022 to have some concentration of our annual revenues similar to our experience last year relative to the second half of 2022. As J. J. mentioned, we reaffirm our annual guidance for Naglazyme and Vimizim revenues. For Brineura 33% growth year-over-year and revenue of $36 million in the first quarter was driven by 18% growth in new patients starting therapy.

Moving now to Palynziq, net product revenues grew 2% in the first quarter as compared to the first quarter of 2021 and were impacted by a variety of factors. In the U.S. seasonality of healthcare coverage similarly to what was experience with Kuvan in the past resulted in a Q1 dip in Palynziq revenues as compared to the fourth quarter of 2021. And while we expect this dynamic in the U.S. to recover for the remainder of 2022, impact from ongoing PKU clinic limitations as full year Palynziq revenues trending to the lower end of the guidance range for the full year.

Continuing with the PKU franchise, Kuvan contributed $59 million in revenues in the first quarter of 2022, down 16% as compared to Q1 2021. Since the loss of U.S. market exclusivity in October of 2020, we experienced a further step down in the U.S. in the first quarter. As Kuvan nears the end of its life cycle as we would expect from a small molecule drug we are gratified to be able to retain the market share and the resulting revenues we are experiencing. Based on market conditions we expect full year Kuvan revenues in 2022 to trend closer to the lower end of the previously provided full-year guidance range in 2022.

Lastly, with the CHMP opinion on ROCTAVIAN expected in the near future launch readiness activities continue to progress. The team is on board and well prepared to launch assuming regulatory approvals later this year we are encouraged that our longer term data results offer a potentially attractive value proposition and treatment option for those with severe hemophilia A and we look forward to providing you with more detailed updates at launch.

In conclusion, in 2022 we anticipate increased demand for all of our commercial brands with the exception of Kuvan as just described. Our products are expected to contribute significantly to revenue growth this year. We also expect VOXZOGO be a meaningful factor in this ramp year noted in today’s increase in VOXZOGO revenue guidance. We believe that robust prescription demand represents a foundation for continued growth including the new markets throughout 2022.

Thank you for your attention and I will now turn the call over to Hank to provide our R&D update. Hank?

Henry J. Fuchs — President, Worldwide Research & Development

Thanks, Jeff, and thank you all for joining us today. The R&D organization has a very busy quarter as well. Our regulatory team has been focused on health authority interactions with the European Medicines Agency on the ROCTAVIAN application currently under review and preparations for the June re-submission of our biologics license application in the United States. We have enjoyed a high degree of collaboration with the EMA as we enter the later stages of the review procedure. Thus far, we’ve been able to satisfy their request for information, putting us on track for a potential CHMP in mid-year this precise scheduling subject to the EMA.

As J. J. mentioned, we were pleased to have completed the analysis of the tumor that was identified in one of our Phase 2 study participants as noted in our presentation this past February. Results are consistent with the benign integration profile for ROCTAVIAN as we did not observe ROCTAVIAN integration associated with growth of the tumor cells. We plan to provide EMA data as part of the ongoing review of our market authorization application as well as include the data in the biologics licensing application in the United States and the re-submission in June. Needless to say, we’re pleased with the findings as it further support the safety profile ROCTAVIAN has demonstrated to date. As leaders in the field of gene therapy, we look forward to sharing the results of the analysis to the scientific community at the upcoming World Federation of Hemophilia 2022 World Congress and the Annual American Society of Cell and Gene Therapy in addition.

Turning to VOXZOGO, we are pleased to share that Dr. Andrew Dauber will present results from in study in genetic central conditions at the Pediatric Endocrine Society Meeting this coming Sunday May 1. As we shared in our last R&D Day, the study stands six different genetic central conditions. So we look forward to learning about the potential of VOXZOGO to positively impact children with other conditions besides achondroplasia. Next milestone VOXZOGO with the data updates from our Phase 2 randomized double-blind placebo-controlled VOXZOGO study and infants and young children up the five-years of age with achondroplasia teams had the opportunity to analyze the results since they were on boarded in February and we expect to share them at a medical meeting in the middle of the year.

Finally, turning to the earlier stage pipeline, all of the candidates under development continue to advance. A new update today is that we have begun dosing patients in the Phase 1/2 HAERMONY 1 study using BMN 331, a gene therapy for hereditary angioedema. We are encouraged by this new opportunity for HAE patients as our pre-clinical data suggests that BMN 331 can reduce the frequency and severity of attacks and potentially eliminate product therapy for some patients, significantly reducing the treatment burden of HAE endocrine standard of care. We’re excited to begin this development journey and learning about potential BMN 331 to restore C1 esterase inhibitor protein in humans based on the encouraging pre-clinical data served.

The BMN 255 which is a subset of chronic renal disease we completed the single ascending dose arm of the Phase 1/2 study and are in the process of analyzing results. Concerning BMN 351 Duchenne’s muscular dystrophy we expect to file the IND in the first half of the year with the goal of treating the first Duchenne boys in the fourth quarter of this year. Our pre-clinical studies of BMN 349 continued our enthusiasm for it’s potential to dramatically improve liver health in people living with A1AT antitrypsin deficiency and BMN 293 formerly referred to as DINA-001 is on track to be our next gene therapy clinical candidate in this case for the treatment of [Indecipherable] caused by mutations in cardiac myosin-binding protein C3. We continue to advance 349 and 293 towards IND in the second half of 2023.

Lastly on BMN 307 PKU gene therapy we await results of non-clinical studies required to remove the current clinical hold. And as we said in January and February we believe that this will be a multi-quarter process. So we’ll update that program status when available. We look forward to keeping you apprised of our progress across the R&D organizations as we advance our ROCTAVIAN applications present data at upcoming medical meetings to move the earlier stage pipeline products forward.

Thanks for your support and I’ll turn — I’ll now turn the call over to Brian to update financial results in the quarter. Brian?

Brian R. Mueller — Executive Vice President, Chief Financial Officer

Thank you, Hank. Please refer to today’s press release summarizing our financial results for full details on the first quarter 2022. As Jeff touched on many of the top line results and the commercial business, I will primarily focus on operating expenses, bottom line results and other key financial update this quarter. As usual, all results will be available in our upcoming Form 10-Q, which we are on track to file over the next few days. As we highlighted in February, we believe that 2022 is an exciting year for BioMarin, as the company anticipates transitions to sustainable GAAP profitability driven by the continued strong growth of our base business plus a significant contribution from VOXZOGO in its launched year. We are pleased to be tracking to plan based on the company’s first quarter results provided today.

Total revenue growth of 11% in the first quarter of 2022 as compared to the first quarter of 2021 excluding Kuvan sets us up nicely to achieve our full meter GAAP and non-GAAP income goal for 2022. To elaborate upon one important comment from Jeff, while we expect Naglazyme and Vimizim orders to be weighted to the first half of 2022 based on the ordering patterns of select market, we expect that our total revenues for the full year will be balanced out by growth in our other brands in the second half of the year and total BioMarin revenues will be roughly even between the first and second half of ’22.

Also comment on VOXZOGO, while we are pleased to observe the early patient uptake trends for VOXZOGO globally, which drove our increased expectations for the full year 2022, it’s important to know that even though we expect to continue to add new VOXZOGO patients over the remainder of 2022 the mechanics of daily dosing mean that these new patients on therapy for just a portion of the year will contribute slightly less to full year 2022 revenue.

Moving to operating expenses for the first quarter of 2022 both R&D and SG&A expense, so in line with our expectations. R&D expenses for the first year were $161 million, a slight increase as compared to the first quarter 2021, reflecting increased ROCTAVIAN development efforts and increased R&D on our early-stage programs. SG&A expenses for the first quarter 2022 were $195 million as compared to $174 million for the same period last year and reflect the global VOXZOGO commercial launch efforts to the European and U.S. approvals in the second half of last year, as well as the ROCTAVIAN commercial launch preparation costs.

Moving to bottom line results for the first quarter, as we shared in February, during the first quarter of 2022 we sold the priority review voucher received with the approval of VOXZOGO in the United States. The transaction was recognized as a gain on sale of a non-financial asset on our statement of operations and was the primary driver of Q1 GAAP net income of $120.8 million, while GAAP profitability in 2022 will benefit from PRV sale, we note that our business plan for the year and the related profitability expectations are not dependent upon the after-tax gain from the PRV sale. With respect to non-GAAP income, Q1 2022 non-GAAP income of $105 million excludes the gain on the sale of the PRV and was relatively flat to 2021 first quarter non-GAAP income $104 million and represents a strong start to our expectation of earnings between $350 million to $390 million of non-GAAP income this year.

Turning to total cash and investments, we ended the first quarter 2022 with $1.5 billion mostly flat to year-end 2021. While our total cash increased with the proceeds from the sale of the PRV, we also experienced quarterly working capital timing differences during Q1 2022. As we had provided 2022 guidance, we do expect positive operating cash flows for the full year. Briefly on the Ukraine crisis given our global footprint and commercial presence in this region, as we previously shared the Russian and Ukraine markets represent approximately 2% to 3% of BioMarin’s total revenue and based on what we know today we expect that to be consistent in 2022. Given the essential nature of our products which treat underlying condition for which no alternative pharmaceutical treatments are available, we continue to serve our patients in the region and are working to minimize the treatment disruptions for Ukrainian patients. In fact, we have already fulfilled the significant portion of the expected 2020 supply to Ukraine and Russia.

In closing, 2022 is off to a great start and we are on track to achieve our transition to sustainable profitability with record first quarter revenues driven by a strong global launch of VOXZOGO and solid growth in the base business. Our plan to support both continued product approvals and innovative pipeline of growth while at the same time generating sustainable increase in revenue, profit and operating cash flow is being realized with an eye towards continued growth further into this decade. Thank you for your attention and we will now open up the call to your questions. Operator?

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from the line of Salveen Richter of Goldman Sachs. Your line is now open.

Salveen Richter — Goldman Sachs — Analyst

Good afternoon. First, congratulations on turning GAAP profitable. Two questions from me. For VOXZOGO, in the U.S., how is outreach and uptake progressing in pediatric and endocrinologist? And then for ROCTAVIAN anything you can provide us on how regulatory discussions are playing out in the U.S. Thank you.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Hi, Salveen. I’ll take the first question. Yeah, we’re doing really well with outreach to pediatric endocrinologist. It is a new call point and as we’re emerging from the shutdown, our teams are establishing connections with this new call point in the United States and other markets where we’re active for example in Germany and we’re seeing prescriptions coming in from a mix of physician specialties as I noted, but mainly from geneticists and pete endos as we would expect. So I would say it’s going right on track with nothing notable to describe that’s kind of surprising or different than we expected.

And regulatory discussions, again the bulk of the conversations have been with European Medicines Agency and we felt pretty good about the connection between the remaining questions they have and the information that we have to provide and including the recently completed genomic analysis salivary gland tumor, which is favorable. In regard to the U.S., we do plan to have even further discussions with the Food and Drug Administration in advance of our re-submission pre-submission interaction is in fact scheduled with Food and Drug Administration. But we’ve also already had quite a bit of dialog since the CRL about information now want us to buy back to them when we do resubmit. We also feel pretty good about the sufficiency of the data that we have in hand for satisfied of the concerns that were raised. So feeling pretty good about the regulatory situation in both markets.

Salveen Richter — Goldman Sachs — Analyst

Got it. Thank you.

Operator

Your next question comes from Chris Raymond of Piper Sandler.

Chris Raymond — Piper Sandler — Analyst

Hey, thanks for taking the question. Just on VOXZOGO, maybe just a couple of questions on the dynamic there. I think with the number guys — you guys gave about a third or so of revenue last quarter was in the U.S. in just a little less than a third of patients. I know it’s early, but is this may be indicative of more sort of parity pricing or is there some sort of patient add dynamic. And then also just doing the math on the revenue and then on the patients that seems to be a relatively high number for the quarter just is there anything you can add there in terms of the pricing dynamic. And if I can ask a pipeline question, no mention of — I think I heard no mention of BMN 307. Can you just give us a sense of where that program sort of sits. Thank you.

Brian R. Mueller — Executive Vice President, Chief Financial Officer

Hi, Chris. I’ll start off on the VOXZOGO question. So you mentioned and confirming that we stated about a third of our revenues from the United States and the balance ex-U.S. which ties up pretty closely to the patient numbers that we’re reporting. Also in the United States early in Q1 we did have some specialty pharmacy stocking which was a one-time event. Not a huge number, but enough so that there is a resting inventory in our specialty pharmacy network, but it’s kind of a one, as I say, a one-time event. And by late March, I would say, we were seeing reorders of our specialty pharmacy network in the U.S. on a consistent enough basis that you would conclude that there is no further buying down of that inventory and that the ASPs were essentially ordering to demand so that could be a little bit of a bump in Q1 and were tilted towards the U.S. And if you followed along our pricing discussion, there was — as usual, we have a robust price, particularly in the U.S. and so far we’re managing it pretty tight price corridor for VOXZOGO and other markets. Does that cover your question?

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

If I may add, so actually the launch has also been going very well in both sides of the expenses and the difference there. I mean, do you expect the difference you see all of it is because we started selling in Europe and Germany actually in October of last year. So we will have the U.S. really started in the U.S. in January. But basically without thing is that the revenues are commensurate with the market — with the market side, and we are always state the largest opportunity without the U,S, and the numbers are confirming that. Also the good news here is that, again, I think there were some anxieties and the lenders report about launching a product first in Europe and before the U.S. it’s a first time we do that and it was actually that we can be very successful launching a product in Europe ahead of the U.S., which is likely to happen for updated. Hank do you want to take that.

Henry J. Fuchs — President, Worldwide Research & Development

Yeah. Chris, the game plan is we’ve got to complete some additional pre-clinical studies that pertain to the findings that have been previously reported the agency. We were hopeful that there are some early interactions with the agency that we would be able to remove the whole quicker, but unfortunately with this requirement to conduct additional studies, we probably won’t have any updates for you on that until we have the results of those studies which are going to be several quarters now. So, I’d say, unfortunately don’t be looking for near-term updates on 307.

Chris Raymond — Piper Sandler — Analyst

Okay. Thanks, guys.

Operator

Your next question comes from Robyn Karnauskas of Truist.

Robyn Karnauskas — Truist Securities — Analyst

Hi, guys. Thanks for taking my questions. So just a quick one I guess for the EMEA discussion and the U.S. discussion, given that you’re adding traditional data, is it possible that we could go into July. I know you’re not on the docket. It looks like so April for EMEA and same for the U.S., do you think that this could take a little longer to filing could be middle of the year like July, August. And then second question is on VOXZOGO. So it seems like you have the same number of patients and process that you did last quarter. Do you expect this and the addition of patients to be consistent or do you think this is more of a bolus upfront and then maybe you can comment on, but maybe you can comment on the compliance given the early — and it’s early but compliance with daily dosing. Thanks.

Henry J. Fuchs — President, Worldwide Research & Development

I’ll take a shot at the first part of your question as to the timeline in the European Medicines Agency. We feel pretty optimistic that all the information of these that we’ll be able to provide EMA the last leg of review will enable them to make a decision in June, but it’s also a decent amount of information and the EMA has based on the questions that they’ve asked the question decent chunk of information standard review in terms of risk management plans, label, commitments and things like that. So, yeah, it could drop into July. But we were getting to be lined up with them and enable them to come to the positive opinion of course of the decade wellness. And in regard to the U.S. you’re right to ask a question to team we will certainly appreciate the nature of the question, which is that are carrying a lot of water on the European application. At the same time, we’re finalizing the U.S. application. So as with execution things and that’s really down execution that sort of things may take a little longer. We really want to make sure we’ll submit an application that will facilitate effective review by the U.S. but that target again it’s in June and we near all remaining on that track.

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

And your question on VOXZOGO, I mean, I’ll let Jeff answer the question or whether it’s bolus of patients over there. The first is very sustainable. We will be, but just elaborate and the compliance. I think we lost only one patient. Is that correct. All the patients we saw it, we have lost one patient so far. Jeff. So, extremely good compliance.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Yeah, thanks Robyn for the question. It’s actually a positive sign of the launch trajectory in the United States, which is the one place in the world that we’re able to track patient numbers in process. So the fact is that our end process is holding steady compared to where it was a quarter ago it’s indicative of getting a steady stream of both of new patients being enrolled and then also having the ability to pretty rapidly work through those patients, get them approved for treatment, get product shipped out and prescription fulfilled. So I view that as a positive. Related to compliance J. J. noted small number, very small number on drop off. So far we don’t have, at this stage, I don’t have a quantitative estimate of compliance, other than the drop-off figure which is supportive of a high rate of compliance so far. The other thing that we’re doing is we’re being very proactive with patients and their families about kind of training for this daily injection and we’ve gotten super feedback in both Europe and the United States. So that’s been really helpful for with families giving them the confidence to go out and begin the daily injection routine. And I think that bodes well for compliance going forward. Thanks.

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

We have very good visibility adjusted in the U.S., because this is basically first and concurrently since the that signify that they wanted to be on the family that involve the kids to be treated with VOXZOGO. So we have good visibility for for the decrease in rates and we have no inside of that. It is those are new patients going to be true that it is going down. And I think and Jeff you want to mention how long it takes between when a patient is signed up and when we start shipping on average in the U.S.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Yeah. So, so far, it’s pretty rapid. Our average is 23 days from complete enrollment with a prescription to shipment of that first prescription to a patient for some variability around that.

Robyn Karnauskas — Truist Securities — Analyst

Great, thank you.

Operator

Your next question comes from Cory Kasimov of J.P. Morgan.

Cory Kasimov — J.P. Morgan — Analyst

Hey, good afternoon, guys. Thanks for taking my questions. Two from me as well. Both probably for Hank. First, just a follow-up on in the U.S. ROCTAVIAN situations. Is there anything specific that needs to be addressed in that pre-BLA meeting that hasn’t been dealt with already. I guess, just curious if this is standard operating procedure for a re-submission or if there are issues to still discussed. And then the second thing I was just wondering, Hank, if you could set the stage ahead of the short stature update this weekend for VOXZOGO, what would be compelling in your view or an investigator’s view when you speak with them. Thank you.

Henry J. Fuchs — President, Worldwide Research & Development

Yeah. I think interaction was going to FDA pre-submission ROCTAVIAN is more of the S&P rather than necessarily, particularly new information. I think the agencies since it’s likely to be these are all issues maybe result during the review. What we — what’s important for us to just make sure that we have clear eye view of the information that they looking for. We have all these data. So it’s really just a matter of make sure it’s in the form of content of what they’re looking for some more on the S&P side. As far as the presentation I think the expectation to have is that in the amalgam that through across a range of mutations. I think reminders these indicators that is accrued patients six different types of mutations that there can be an improvement in as measured by the HGB in children who have mutations that are different from the achondroplasia FGFR communication and got a lot of biology as to why he believes that to be the case for the course of data itself themselves will be this positive words is underlying. So I was focusing on the HGB change from baseline, the process, different types of mutations that is included and I think the — a good a good outcome would be similar or better that similar to what we’ve seen in achondroplasia great outcome. And I might be indication specific might be that some inflation driven more responsive to this very tight. So I think that’s the stage is set for the current data.

Cory Kasimov — J.P. Morgan — Analyst

Great, thank you.

Operator

Your next question comes from Paul Matteis of Stifel.

Henry J. Fuchs — President, Worldwide Research & Development

Sorry, we couldn’t hear.

Paul Matteis — Stifel — Analyst

I think she said, Paul Matteis at Stifel. Thanks a lot for taking the question. Good to talk to you. Just one VOXZOGO question on the commercial side. I guess are you think physicians or do you think physicians will do anything to determine whether or not patients are benefiting. Obviously, you can look at growth natural history of every patient is different. You can given the hypothetical. So maybe just comment on how you sort of verify efficacy with this drug. And then to the extent you’ve seen any discontinuation so far what are the reasons if you wouldn’t mind clarifying. Thank you.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Thanks for your question Paul. So at in terms of tracking benefit that’s not something that we guide specifically to, but we would certainly expect physicians will be following along the progress of the patients. There is newly published guidance on the management of achondroplasia which I think is helpful in providing those prescribers the guidance to do that and growth velocity and high would be kind of a lowest common denominator that could be expected. Some of the U.S. insurers are requiring evidence of benefit for future renewal of prescriptions for example which seems reasonable enough. And back to the publication on management guidelines, as you’ve heard me say before, really there was no medical home particularly in the U.S. in our system. No medical home for achondroplasia patients. And I think part of the opportunity here is to establish a medical home for kids with achondroplasia up to and including but not limited to be use of VOXZOGO as a part of that overall management scheme. And I think that’s going to be good for BioMarin and VOXZOGO and it’s going to be great for the kids with achondroplasia and their families. In terms of discontinuation, we really have enough data as J. J. momentum. I think we have one discontinuation, and I have a stated reason for that one.

Paul Matteis — Stifel — Analyst

Okay, thanks. And then maybe just one, sorry, go ahead.

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

I think if you go back to tracking the efficacy and this is not a — when you do it, is just an anecdote that when we tested the advertising campaign with European healthcare professionals and patients we actually have and we have a picture of the young girl who have been treated with VOXZOGO for I think over four years, very close to five now and she is obviously what she the aggressive patient. And the reactions from the panels doctors and families of take on patients as well that we should be using really patients for advertising. That’s my all the way to answer your questions.

Paul Matteis — Stifel — Analyst

Thank you, J. J. And last, just one quick thing, any update on the path two full approval. Thanks again.

Henry J. Fuchs — President, Worldwide Research & Development

And in particular the good news is that we’re the data that’s going to generate the core group package is going to be did you follow up these patients from the pivotal clinical trial. And as you just heard the compliance in the program overall is pretty excellent. So we do expect to be able to provide that in a timely fashion. I don’t know that we’ve guided to a specific submission.

Paul Matteis — Stifel — Analyst

Understood. Thanks again.

Operator

Your next question comes from Gena Wang of Barclays.

Gena Wang — Barclays — Analyst

Thank you for taking my questions. I have two sets of questions. So the first one is regarding the ROCTAVIAN salivary gland mass integration analysis. So you saw similar patterns, but did you see any unwanted site that show up in this analysis? And a related question for your 307 PKU program your analysis also showed integration not tumor initiating event but FDA’s do ask for data that require several quarters of work. So what makes you confident that similar situation won’t happen here to our ROCTAVIAN. And I have quickly on VOXZOGO question, just wondering what is the price range for the ex-U.S. different countries and for France now you have like listing prices, a $300,000, but since you expect future negotiating price will be lower, how would you book the revenue here.

Henry J. Fuchs — President, Worldwide Research & Development

Hi, Gena. So as regards that pattern of integration there really was something particularly noteworthy about the pattern of integration and that I think the key is to compare the pattern of integration between the healthy tissue in the adjacent of to the tumor tissue. And as has been previously described core wild-type AAV recombinant vectors have a relatively low capacity and integration. And I think that’s that has been foundational the regulatory perspective. You might remember, there was an FDA guidance them on this and they refer to AAV vectors is having a low propensity for integration. I think one of the great things about what we’ve found so far is that in a appears that the recombinant vectors saving similarly in terms of distribution integration patterns and frequencies and size of integration similar to the wild-type that is to say, not binding preferential hot spots of particular relevance.

And so that’s part of your question was the 307 how does that read are effectively. I understood the question would be, how does it need 270 evaluation and why not the management be the similar requirements for 270 as there have been for, as there appear to be for 307. I think the short answer to that is because the 270 vector has cleared its safety studies for the out I think satisfaction of our there have been the only sort of sufficient signal and that 270 programs what we just talked about, which was the product tumor and there is nothing unique, particularly in the findings in this individual. And so I think having that seen us with neither by the pre-clinical ROCTAVIAN itself nor with these vector that is construction is very, very similar ROCTAVIAN and studied for a longer period of time in the ROCTAVIAN study that similar that similarly is not oncogenic and pre-clinical species.

So I think all these things take together — taken together bodes quite well for the ROCTAVIAN overall risk benefit evaluation, namely that in pre-clinical studies in humans, no particular confirming signal of oncogenic potential of the vectors statistics. And clearly the FDA is seeing these two products really differently suspected although 270 is on clinical hold ROCTAVIAN is not on clinical hold. We are rewarding — this is studies as we speak nor as same as 331s either also enrolling and therefore I think it agency is reacting this is a vector specific indication specific decision. And you had a question on the revenue, price range of VOXZOGO in Europe and revenue recognition. He was always Jeff and then Brian expect.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Regarding the price range G&A, the prices but we’re anchoring to, we’ve got the WACC price in the United States spend in our approval call we guided to our expectation of growth or WACC price to net realizable price per patient. I think that’s a pretty solid estimate. We’ve got the list price as you know in Germany and France and our expectation is that it’s going to take about a year from product introduction to get to kind of negotiate it prices for full reimbursement. So that will happen later this year and then the meantime where we’re establishing pricing for our named-patient sales markets our are right in a pretty tight quarter consistent with the US French and German pricing and I’ll let Brian cover the the discount piece.

Brian R. Mueller — Executive Vice President, Chief Financial Officer

Yeah, thanks, Jeff. Thanks for the question, Gena. This is Brian. There is nothing materially unique to speak about with respect to VOXZOGO gross to net. Our experience in our expectation, though, that the overall gross to net will be similar to our other products as well as our prior launches, not to get into each of the European country by country dynamics, but in some cases you do start within an initial price and then there could be a call back and you give to their final negotiated price it’s lower, but we are required under GAAP to to make estimates of those and recorded those reserves, if you will, So, what you’re seeing in our reported revenue would be the net, net revenue.

Gena Wang — Barclays — Analyst

All right, thank you. Very helpful.

Operator

Your next question comes from Geoff Meacham of Bank of America.

Geoff Meacham — Bank of America Merrill Lynch — Analyst

Hey, guys. Thanks so much for the question. I just had a couple of a long kind of the same things as everyone has been asking. Hank on ROCTAVIAN, I know it’s pursing the language a bit, but it is the shift from 2Q to mid-2022 from the CHMP, is that’s just the normal fluctuation or was in fact there an impact to the review clock when you look at the tumor analysis. And then on VOXZOGO commercially, I know it’s early, but are there some themes that new patient starts in Europe who weren’t in the clinical studies in terms of patient flows or awareness. I’m just trying to get a sense for what was working there in this early in the launch and maybe if that could be similar or different when you look at the U.S. launch. Thank you.

Henry J. Fuchs — President, Worldwide Research & Development

Geoff on the earlier, there is no concrete piece of information that is underneath the shift, if the buyer side regarding June maybe shifting into the summer. I think the only news here is that’s news is we’ve been off that we just came off accelerated assessment and that was anticipated. But you never know, at the beginning of the procedures and the number of procedures just sort of how their timelines line up and when they want to receive information. And so I think as much as anything we’re just now a little abundant caution here in terms of that projecting losses not entirely in our control as a result of the fact that we’re giving them a pretty big slug of data towards the tail end of the review. They obviously knew its coming. So that’s why we’re confident that we’re stay in the procedure and that we’re going to have an opinion by the summer, but it also is like got follow their lead in terms of exactly when they’re going to take you through the business. And the most important thing is we believe we have the information that address questions they’ve issued to us. And based on those questions we believe that a positive benefit risk can come, but that happens after they’ve done their needs for source. So that’s what we’re working to support.

Geoff Meacham — Bank of America Merrill Lynch — Analyst

VOXZOGO European business.

Henry J. Fuchs — President, Worldwide Research & Development

Yeah, so, Geoff, what I would say about themes is diversity of experience here with which points kind of away from common themes in an important way. Diversity, I would say, diversity of age group that we’re seeing starting therapy. One example diversity of prescribers specialty that we’re seeing mainly in generics and pediatric endocrinologist but also some pediatric orthopedics and pediatricians showing up here and also kind of diversity of approach. So in Germany, we were essentially operating under a full price of reimbursement approval, even though we haven’t negotiated a final price, they are, it’s kind of how the market behaves. And so we’re seeing pretty rapid uptake in France. In contrast, we’re currently operating under a very structured expanded access protocol there. So it’s a more kind of structured approach to getting patients started and from relatively small network of clinics.

And then France as I’ve noted before the physicians, they are actually starting older patients in working down of age on the logic that they want to take full advantage of the window for treatment with their older kids that’s not really something that we’ve seen anywhere else. And in the smaller named-patient sales markets I would say that the, there is, we’re getting one or a couple of patients approved initially under named-patient sales approvals and our opportunity there has been to kind of build off that the third, the fourth, in some cases the fifth or the eight patients treated, and we’re working hard to do that. So a lot of diversity actually of experience.

Geoff Meacham — Bank of America Merrill Lynch — Analyst

Got you. Okay, thanks guys.

Operator

The next question we have Phil Nadeau with Cowen.

Phil Nadeau — Cowen and Company — Analyst

Good afternoon. Let me add my congratulations on a productive quarter. Just a couple of follow-ups from us on VOXZOGO and ROCTAVIAN. First on VOXZOGO, Jeff, I think on the approval call you identified one of the challenges of the U.S. launch that a lot of patients weren’t an expert centers. Are the expert centers reporting that patients are inquiring about being treated or is there a general flux of patients towards the expert centers with the availability of VOXZOGO? And then second on ROCTAVIAN Hank just briefly what are your expectations for an ad com. I know there wasn’t one in the first review, do you think the FDA’s like good home to review the ROCTAVIAN re-submission. Thanks.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

So I’ll start on the VOXZOGO experience in the United States. You’re right, when we — on the approval call I noted that longer term, our big task was to establish a referral network and kind of get patients out of random physician, which is not a medical home for achondroplasia get them referred either to genetics clinic that’s interested in achondroplasia or to a pediatric endocrinologists and and months ago I mentioned that’s an opportunity to create a treatment home for achondroplasia. And also earlier I said, we’ve got a pretty steady rate of patients coming in the United States for referrals and in process group and and that’s a good signal indicating that we didn’t just have a bolus of patients that were often slowing down over time. However, underneath that I think you’re right a lot of our early patients were coming from the generics and skeletal dysplasia clinics expert centers that had achondroplasia patients lined up. So a lot of interest and referrals early on for Matt channel. And in the last couple of months and we’ve been able to get that referral network established in the U,S, and start driving patients from a random physicians that they’re being seen by two pediatric endochronologists so that’s picking up now and I think that’s going to be the longer term driver of growth for the U.S. market.

Henry J. Fuchs — President, Worldwide Research & Development

The issue of end council I don’t know that they have like meaningfully more information to add to dialogue since the agency won’t really decide the ad com until they’re in review. I mean, I think if you’re asking personally what would he say, I’d be something like agency called and it comes generally for two purposes. One is, when they want to approve something and they want to rally the troops around the decision they make, and then the other is when they want to wait something and I want to use the ad come to it. It feels like there’s not a lot of info that the could show to an ad com because the efficacy profiles because the safety profile is good and so what would you point to be the most fulfilling it. So, I guess, I could say, I hope you can call on, because I think that what they are doing is going to be serious about like how they regulate gene therapy products and use the fairly robust package ROCTAVIAN to establish standards for review, but we will be worried.

Phil Nadeau — Cowen and Company — Analyst

That’s helpful. Thank you.

Operator

Your next question is from Matthew Harrison of Morgan Stanley.

Matthew Harrison — Morgan Stanley — Analyst

Great. Good afternoon. Thanks for taking the question. Jeff, I just wanted to follow up on two things. One, I think you talked about some inventory dynamics that help blocks over this quarter at the specialty pharmacy. Could you or maybe you’re willing to just quantify or give us some sense about how much that helped. And then secondly, just as you’re preparing for ROCTAVIAN in Europe, can you give us some sense of how much work has been done so far and how much engagement you’ve had with each of the countries around or if any engagement around price and just sort of initial commentary there. Thanks.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Okay, thanks Matt for the question. So, back on VOXZOGO in the U.S. And Kind of arresting specialty pharmacy inventory, you could judge from the mix of revenue ex-U.S. and U.S. and say well, BioMarin is guiding the $7 million of revenue with U.S. I also said that by March we were seeing orders that indicated to be that specialty pharmacies are not drawing down that resting inventory. We also know specialty pharmacies don’t like the whole a lot of inventory and really, they don’t have to because we’ve got really good reorder dynamics for them. So I might I might guide to a couple to several million dollars of resting inventory in the United States.

And then with more to ROCTAVIAN in Europe, one of the things that I think the VOXZOGO launch in Europe is doing is validating that whether there is a large market opportunity and you have an experienced company with experienced teams that know what they’re doing. We can capitalize on that market opportunity and have successful launches in the EU. In particular, we’re leveraging all of the experience that we’ve gotten from the past launches as in the United States. We formed specialized teams to prepare for ROCTAVIAN including seating our teams with people significant experience in the hemophilia business. We’re essentially ready to go in, particularly in the markets where we’re expecting first revenues. And you might expect from the current and past experience that would be in places like France and Germany and Italy first and in places where we get main basin sales uptake on a relatively rapid basis. So we’ve got people in those places.

Yes, we’ve been doing price research. We have an active program working with market access advisers in Europe. We followed that practice, for example, with VOXZOGO. We’re doing the same thing with ROCTAVIAN. I think we’re really ready for this launch and we’re excited about it if we get a CHMP positive opinion and you see approval here.

Henry J. Fuchs — President, Worldwide Research & Development

Hey, if I may add a few things we — so in Germany at least the launch being a price versus the U.S. price or on $2 million and we also just done a lot of research. There is is major interest by driven payers about how can beat a business and we will be making those available because now we have great data showing that majority of the patients do we recall due to through ROCTAVIAN and very few of them. They are lower single-digits are either not responding or go back to prophylactic that are a few years, so we can maximize the price that launch basically operating a guarantee of success in the career, and that’s something that we understand very well on the are very interested in considering that know how much the pieces are helping them. So that’s kind of the plan.

Operator

Your next question comes from Joseph Schwartz with SVB Securities.

Joseph Schwartz — SVB Leerink — Analyst

Hi. A lot of my questions have been answered. So I’ll ask from things about your mid-stage pipeline. I guess it’s been over a year since the IND was filed for BMN 255. So I was wondering if you could give us an update on this program. I see you completed the SAT work, do you think you’ll be advancing today MAV the portion and when can we expect to see some data there, is it possible to see signal from the trial, even though these are healthy volunteers.

Henry J. Fuchs — President, Worldwide Research & Development

I guess all good questions, Joseph. The early stages, a small molecule development are sort of often times is the twisty as part of the roads. So, I think I can share with you now is which we putting your question which is the completed the single ascending dose portion of the study and we’re analyzing the results that. I think the excitement for 255 is it’s generic enablement, namely that we understand there to be a molecular pathway that’s regulating oxalate excretion and you know there’s a lot of oxalate excretion and recurrent stone quarters people with chronic renal disease that we really figured out a way to open the tap on oxalate it should be. It should be, or I should say close that it should be sort of the professions but stay tuned as we gather data and this particular twisty days of the program.

Joseph Schwartz — SVB Leerink — Analyst

Okay, thank you.

Operator

Your next question is from Debjit Chattopadhyay with Guggenheim.

Debjit Chattopadhyay — Guggenheim — Analyst

Hey, thank you for letting me in. So just on VOXZOGO on the commercial launch so for, upper age limit of patients who are currently getting prescribed, and number two, any clarity on the sleep apnea signal noted in the younger subjects in the 0 to 5-year-old study, and finally, are you planning to advance the long-acting version in the clinic. Thanks so much.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Hi, Debjit. I’ll start with the question on the age range. As noted earlier, I think we’ve seen where we have the data to measure it quite a lot of diversity in age range including teenagers being enrolled for treatment as well as younger kids. So don’t have a ceiling on age. But what we know is kids that have place close will not benefit. So we would expect that upper limit to be something plus or minus or 18 years old plus or minus. And I think the your second question was related to the 0 to 5 year old. Yeah, so biggest possible picture on the 0 to 5-year-old is that in Europe certain launched Europeans were compelled by an overall package data in the signal data that we provided to them during the application.

So, we have enabled and we can [Indecipherable] 0 to 5 year old population. In the United States FDA want a little bit more information on the results of 206 going to inform that we’ve announced positive trends were observed, and I think in the treatment of these young children I think the next step airport is to have conversations with Food and Drug Administration about labeling requirements. We’re going to pursue a similar pattern throughout the rest of the world. We believe that support giving families treatment option for children who are under 5 years of age with achondroplasia and working with health authorities by given the information that they need to come to that decision and different geographies may come to that decision at different time point based on emerging data. So I’d say stay tuned for further updates from us on both regulatory plans as well as overall plans for addressing.

Henry J. Fuchs — President, Worldwide Research & Development

And we are in a decision of the review in Japan for our position that the finding is for [Indecipherable] So and also insurance. But when the so we’re data will be presented.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Yes. So there we present. I think we said somewhere on the call. And then I think you about long-acting. And long-acting I think so far about it is not much of an efficacy advantage in most children much of the safety event. We’ve talked about all the numbers behind all that. It is an interesting question, as it pertains to the children who are under 5 you might know that has in the Phase 2 study. And we’re also patients who are under 5 so there could be some data about the effect of long acting on overall growth. But again a key reminder about that is how far behind us the is really is in terms of selling happen. This is a relatively small Phase 2 study. So I think we have some room to those offer this option on a global basis for young children, because there is nothing else and time is of the essence as well as to further integrate our product offerings to continue building strengthen in the VOXZOGO brand.

Debjit Chattopadhyay — Guggenheim — Analyst

Thank you. Good luck.

Operator

Your next question is from Joel Beatty with Baird.

Joel Beatty — Robert W. Baird — Analyst

Thanks for taking my questions. The first one is for VOXZOGO, what’s the level of awareness of the drug among patients with achondroplasia and their families? And then also for 351 for DMD, what will be learned from the initial study starting later this year?

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Maybe I’ll start with the question about level of awareness. That’s something that we would typically be market researching and to get a quantitative estimate following launch and the answer on that one is we haven’t yet gone out to market research that question we will at some point during the year and the way that we do that work have an estimate. Qualitatively I would say it looks to be pretty high based on the level of patients that we see coming in for treatment. What we learn from the initial 331 study, as I said, our goal is to get into the treatment of DMD boys as quickly as we can of them by the end of the year and outsource that’s always subject to regulatory review of an IND. But assuming that that’s the plan I think and that should be the plan because the central question really is, what’s the relationship between to deliver dose its safety profile and the level of dystrophin increase that you can achieve, and based on the biology of the compound that we’ve developed, we believe that the nature of the chemistry being so similar to what we use with drisapersen that we should be able to achieve tissue concentrations, muscle tissue concentrations of our 351 compound that was produced skipping in the range of between 20% and 40% meaning that the patients would have 20% or 40% of this shorten dystrophin protein, which is in a pretty high relative to what ambulatory patients with far less severe condition called Becker’s dystrophy, muscular dystrophy have. So as quickly as possible the [Indecipherable] one proof of concept study will gear itself towards demonstrating safe improvement a sit — on a meaningful quantity of dystrophin protein and muscle. Take you timeline specifically to one, they will be available as we’re just get concerned.

Joel Beatty — Robert W. Baird — Analyst

Thank you.

Operator

Your next question is from Luca Issi with RBC Capital.

Luca Issi — RBC Capital Markets — Analyst

Well, great. Thanks so much for taking my question. Quick one on valrox. I know you’re ruling out AAV is the potential cause of the salivary gland cancer, but can you actually share the integration frequency that you have observed on the surgical piece. I know UniQure mentioned in the past is 0.027% of their cell showing evidence of AAV integrations for their carcinoma case. So just wondering how you’re number compares to that number. And maybe also related I think AskBio and they have reported a case of tonsil cancer in their hemophilia B program so wondering if — how are you thinking about read through for your program. And then still on valrox, assuming it does gets approved, can you remind us what’s the latest thinking on pricing strategy. And feel free to dichotomies the answer between the U.S. and the EU should that makes sense. Thanks so much.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

I think specifically as regards numbers come to the presentations that are around the quarter at both severe patient the way I think about it is that what we’ve seen so far is consistent with what’s been previously described as low propensity for integration. So qualitatively anyway that’s the frame take into your review of those presentations. As regards the occurrence of other tumors, I mean, I do you think that over time there are going to be patients developing cancer. I mean what’s the effect of getting older in life. And I think that what we’ve seen to date doesn’t really suggest that there’s any particularly clustering of tumor types. I think also one has to really consider sort of vector at a time. That’s kind of what we learned in our 307 as we’re talked about earlier, that is to say, the agency is proceeding with 331 and 270 enrolling clinical trial, it’s only 307 in which the question is kind of raise.

So instead of sort of lumping everything I think the agency is taking each sector clinical situation sort of on its own face for the time being, I think the data that we’re talking about today are pretty encouraging as regards to reaffirming what we’ve known all along about AAV relatively low capacity for integration, relatively low specificity for integration events in particular start from the genome and no reason to believe fundamentally that what’s been observed with AAV. People run around talking about the cancer risk of hepatitis C or hepatitis B. AAV is of the concern that people running around talking about stomach cancer risk from. So I think that low propensity in from of integration to reparation that we’re talking about today is really a powerful finding.

Henry J. Fuchs — President, Worldwide Research & Development

Yeah. I mean, we recovered already previous question the pricing in U.S. and probably in Europe. So I don’t think we need to go over that again. But in order to say a few words about the U.S. pricing just.

Jeff Ajer — Executive Vice President, Chief Commercial Officer

Yeah. So, what you’ve heard J. J. say publicly a couple of years ago was probably not less than $2 million at WACC probably not more than $3 million, but that’s the range that the ICER first review and showed ROCTAVIAN to be a dominant choice sort of presume price of $2.5 million kind of worked up. We’ll announce a final price. When we get an approval and launched. So, I think generally those ranges look pretty solid to me. Let me just one other comment on pricing in our ability to capture a premium price. J. J. mentioned outcomes based agreement earlier that’s crucial to our ability to capture value for ROCTAVIAN payers — in addition to wanting their patients to do well to not lead to not have to infuse 2.5 times a week on average. Payers are concerned financially about the risk of nonperformance following administration and the risk of durability of effect over time. The data that we have so far would suggest risk of nonperformance following administration is very, very low and the durability data that we’ve seen both out of the 201 and the generate 1 study, including the 17 patients that we have three years at is really encouraging, about the durability of effect over time. So we think that we can largely take those risk off the table for payers and that’s one of the factors that will allow us to capture at a high value initially. Thank you.

Operator

This concludes the Q&A session. I will now hand it over to J. J. Bienaime for closing remarks.

Jean-Jacques Bienaime — Chairman and Chief Executive Officer

Thank you, operator, and thank you all for joining us today. We are again pleased to begin 2022 with a record first quarter results and the addition of VOXZOGO to our commercial portfolio is definitely an important component of our growth story going forward and improves the weight on GAAP profitability, sustainable GAAP beginning this year. We have successfully transitioned our focus to the development and commercialization of two therapies for larger conditions and we are hopeful that 2020 will be the year that ROCTAVIAN will be approved in the U.S. and Europe, and we look forward to hoping you, sorry to keep you apprised of our progress over the coming weeks and months. So thank you all for your continued support and we look forward to seeing you soon.

Operator

[Operator Closing Remarks]