Jeffrey Ajer: So let me start out, and I’ll ask Brian or JJ to round out anything I missed, Chris. First, with respect to the CDx test completed, you’re right, it was 2 months ago, actually, that we reported that we had 10 patients that had been submitted for CDx testing. So you could look at that and say, over the past 2 months, we’ve seen an additional 8. And I can tell you because I review the situation with the team every week already have additional patients in motion this week. So what I’m seeing is the development of a patient pipeline and it was slow to get started. It was for sure impacted by patient awareness or the lack of patient awareness immediately following approval and our ability to influence patient awareness in Germany.
The cadence of when patients come in to see their hematologists for hemophilia guidance, which is anywhere from every 3 months to every 12 months. And that cadence of patient hemophilia treatment centers didn’t change just because ROCTAVIAN was approved. So I would say that, that building of the patient funnel and all the things that are happening underneath the top of that funnel are really encouraging to me. I’m seeing movement literally every week now and that movement every week that I’m seeing is picking up pace. So I’m pretty encouraged by that. In terms of guidance, guidance was impacted for ROCTAVIAN by the pace and timing of getting first patient treated, which is different than we were expecting at the beginning of the year, and the change of the PDUFA date in the United States from the end of March to end of June.
Brian Mueller: That’s right. This is Brian. Thanks, Chris, just to supplement that. We noted that the high end of the previous range accounted for the current March PDUFA. And just a reminder, with — what was the March PDUFA at the time. Just a reminder that while that’s a 3-month shift with a product like ROCTAVIAN that we expect to ramp up in terms of revenue over time, that 3-month shift from a revenue standpoint actually causes us to what would have been the last quarter of revenue in 2023. So — and likely the largest quarter. And then on the bottom end, you’re right, there is a combining effect of the challenges in Germany. So we’ve tried to account for all scenarios in the revised guidance.
Operator: Our next question comes from Phil Nadeau from TD Cowen.
Philip Nadeau: One more question on Germany. I guess it’s still unclear was why those patients who have gone through CDx testing have not gone on therapy. I think you’ve been very clear about the price or the reimbursement negotiation process, but you’ve also suggested that there are patients who are covered through OBA — 1 OBA or Named Patient use. So for those patients who have gone through CDx testing, why have they not been treated yet? What’s the bottleneck there? Is it a concern about time to reimbursement? Did the physicians have some other concern kind of what’s preventing that for you? And then secondly, I think you said in your prepared remarks, you do expect the first patient to be treated in Q2. What gives you confidence in that given that no one was pictured in Q1?
Jeffrey Ajer: Phil, I’ll start with that one and see if JJ wants to round out any comments. So what’s going on between CDx testing and treatment, the first thing is CDx testing is one of a couple of eligibility criteria. So it’s an important one, and it’s probably the biggest piece to get done. There’s also liver health testing that’s an eligibility criteria. It is possible — it’s likely — highly likely that anybody that’s going through the process of CDx testing is interested in potential treatment with ROCTAVIAN. As has been described to me by some of the German physicians, the cadence of decision-making may not just hinge on a positive or a negative CDx test. It’s possible. But as described to me, patients go back, they confer with their family, sometimes they have additional questions for their treating physician.
Sometimes they come back for additional appointments to discuss and be canceled on ROCTAVIAN as a treatment option. So I think it’s an important but not the only part in the process of what I might term the purchase decision of a patient for ROCTAVIAN. And then the second question, what gives us confidence in first patient tested in Q2? So in the previous questions, I was subscribing that we’ve got a patient funnel now that is 18 and growing. And if you said, well, emergence of a patient at the top of the funnel is defined by sending sample in for CDx testing. And then I just describe maybe some of the other steps along the way, additional liver testing, conferring with family, thinking a big decision over, maybe coming back into the clinic for further counseling.
Those patients are working down the funnel that leads to the purchase decision. And as I said in the previous question, every week, I see updates and movement in Germany and the pace of those movements is picking up all the time. So that’s what gives me confidence that we’ll have shortly a first or more than 1 patient coming out of the bottom of that funnel for treatment.
Jean-Jacques Bienaime: Maybe I want to add to what Jeff said. I mean, first of all about a year to get in Germany in competitive markets is the norm. So there is nothing that’s surprising here. Again, we thought with an OBA, we would be able to get usage a little faster. But obviously, it’s been difficult. So we did sign another year agreement mainly with 1 payer that only represent about 10% of the German covered life. So 10% of 18 patients will be like 1 20 patients. So it’s not that surprising because the other patients basically are not covered by at existing OBA. So for the other patients who are dependent about a different insurance company. In Germany, physicians are personally liable financially for prescribing a treatment or a procedure that is not where they don’t have coverage from their And obviously, here, we’re talking about $1 million or so cost of therapy.
So obviously, you understand why physicians want to double and triple shacks that the healthy insurance company of the patients will cover the procedure before they move forward. I think all this is being debugged and it’s going to be happening. So this is right now based on the growing pipeline of patients that we believe we’re going to get a patient treated at least in the Q2 of this year in Germany, and then there are patients potentially can talk about in the rest of the world. And then the other thing that Jeff forgot to mention is regarding what happened in the past few months since we gave the previous update about 10 patients that have been screened In Germany, I understand we take Easter holidays very seriously. So for 2 weeks in early April, there wasn’t much activity going on anywhere in the in Germany.
So that also explains. But it looks like since we passed Easter and look like things are picking up again in terms of test screening, so which is very positive.
Operator: And our next question comes from Jessica Fye from JPMorgan. .
Jessica Fye: I have one more on ROCTAVIAN and then another on VOXZOGO. So I think you mentioned you expect the first German patient to get ROCTAVIAN in the second quarter. But maybe more broadly, can you just help us understand your expectations for ROCTAVIAN uptake in Germany between now and September when you get that final reimbursement? And I guess like apart from a patient here and there, does this update about not pursuing OBAs? I mean that we should expect very modest uptake in Germany until the fall. And then separately on VOXZOGO, can you share your latest thinking about the most likely path to approval for settings like hypochondroplasia?
Jeffrey Ajer: I’ll take the first part of that, Jessica. So relative to the subject of uptake, I started out by saying our plan was to facilitate early and more rapid uptake for ROCTAVIAN with these outcomes-based agreements. We tried that, and I think it was a good plan, but things didn’t work out according to that plan. So I think we’re resetting expectations about the pace of uptake. The time — certainly, the timing of first update, which I think is likely in Q2 of this year. And as JJ noted in the script, the fact that we’re deemphasizing or deprioritizing those Outcomes Based Agreements in favor of the full federal process probably means that we’ll have slower uptake until we get that price finalized. It doesn’t mean that we won’t have any uptake because we’ve got 1 agreement in place and there is a process for physicians to submit patients that they want to treat to their insurer for individual review.
So that’s kind of our qualitative expectation there. I’ll turn it over to Hank for the VOXZOGO question.
Henry Fuchs: Path to hypochondroplasia, other new indications for VOXZOGO, pretty exciting question on time because VOXZOGO’s tremendous activities regulator bond growth and because of the unmet need of individuals who have severe impairments in bone growth, resulting health outcomes — poor health outcomes. And the path includes both generating some additional pilot data, which we’ve shared a little bit of, but we’re generating more of that data to increase our end your confidence in the potential for ROCTAVIAN — for VOXZOGO to add value to patients with skeletal impairments and also dialogue with health authorities around requirements for registration. As far as our next steps with the stakeholders, probably the next real meaningful update you’ll get from us about the back and forth that we’re having with health authorities is going to be when we finalize our plans, and we can tell you what the trial is going to look like, when it’s going to start, how many patients are going to be involved, what the endpoints are going to be, what if any of our comparators or concomitant medications in the trial.
So pretty exciting time, and stay tuned. We’re well underway.
Operator: And our next question comes from Akash Tewari from Jefferies.
Akash Tewari: Just on the upcoming readout, is there a potential the FDA may require you to run a trial head-to-head versus growth hormone? And kind of what’s your confidence that efficacy won’t drop off as we go to 1 year and beyond? Obviously, that didn’t occur with achondroplasia, but with these new growth disorders, that’s a question that does come up. And then I also noticed you had 11 patients in Argentina screen for AAV5 antibodies. Can you walk us through a reasonable launch time frame and price expectations for markets outside of the U.S. and EU5?
Henry Fuchs: I’ll start, Akash. Your one question on I had about 5 subparts, but I may not get them all. But one is what will be expected of us in regard to durability demonstration for non-achondroplasia indications. And another part of your question is, will the agency require comparators, for example, with And I think the answers to both of those questions are a little bit TBD in the sense that we are in discussions with the agency. And as I said, we’ll tell you what sort of the resolution of all that is in regard to more specifically the answer to your question by specific type of indication. But I think you also put your finger on the head of the — a figure on the actual pulse of what the issues to address are. And I think one of the really exciting things about VOXZOGO as a natural regulator bone growth is that even in a severe skeletal dysplasia like achondroplasia, we were actually able to demonstrate sufficient durability to satisfy the agency, the FDA, that at least the changes that we saw in AGV were, in fact, reasonably likely to predict a long-term accumulation of a clinically meaningful height benefit.
So I think that is a good platform you referenced that. I also think the issue about growth hormone is that outside of growth hormone deficiencies, there isn’t great evidence about accumulated benefit of growth hormone as regard — well, there’s actual — let me qualify that. There is a lot of evidence about the cumulated height benefit of growth hormone in nongrowth hormone deficiency syndrome. It’s not very compelling evidence that is to say that there isn’t much of a height gain in regard to what growth hormone can do for children. We don’t have growth hormone deficiency. So I think you take all that together, and these are going to be the kinds of discussions that we have with the agency to chart the path forward for new indications for VOXZOGO.
It’s not without complications, but I think the settler for all of this is a medication like VOXZOGO has the property of being a natural regulator bone growth.
Jeffrey Ajer: To your second question, Akash, about what’s the significance or whether we read into those 11 CDx tests in Argentina. I would say in the general sense, Named Patient sales in the absence of or even prior — just prior to a registration is an important part of our commercial picture overall. Witness, for example, the rapid uptake across our commercial footprint with VOXZOGO, some of which, but not all of which, is in markets where we have registrations. We don’t tend to talk about those markets a lot in detail because they tend to be smaller and come at a slower pace than, for example, the major markets in Europe, Japan or the United States, but they’re important overall. And I think Argentina, with early signals of patient movement, a first prescription is a good representation of what we might expect also in other markets where we get going one patient at a time on a Named Patient basis.
We also mentioned that Saudi Arabia, which is also usually an early mover like Argentina on the Named Patient sales basis is, we also are underway, and there’s interest in ROCTAVIAN in that market. So what we’re trying to do here is highlight the fact that beyond where we have very specific plans like in Germany, France and Italy that I’ve mentioned, there is movement in those other important Named Patient sales markets.
Operator: And our next question comes from Joseph Schwartz from SVB Securities.
Joori Park: I have a question on ROCTAVIAN. I’m Joori dialing in for Joe. How is the process with the single public insurance funds in France and Italy going? And can you provide any more color around your expectations to secure reimbursement and access to ROCTAVIAN later in 2023?
Jeffrey Ajer: Joori, so the process in each of France and Italy, which in our commercial footprint with our kind of capabilities, it is always a close follower to Germany in terms of timing and prioritization. Those markets essentially take a year, sometimes longer to get price and reimbursement approval. And right I mentioned, as soon as we got our price listed in Germany, we submitted the full price and reimbursement dossier there and got the process going last fall. Right after we did that with Germany, we were submitting in the fall of last year for France and Italy. So both of those processes are ongoing. There’s no guarantee as there is in Germany that you’ll conclude in 12 months. But we’re on track in both of those markets, and we think it’s likely that we’ll be at the end of that process by the fall of next year.
And in the script, we mentioned this year — and we mentioned in the script that in Italy, and this is breaking news, it just happened last week that we were granted conditionally innovative status for ROCTAVIAN, which doesn’t confer anything specific, but as is in the general sense, a positive signal to how the — how is looking at ROCTAVIAN in Italy as an example.
Operator: And our next question comes from Gena Wang from Barclays.
