And it’s really very clear that the most important thing for patients and caregivers and equivocally is safety and efficacy, and they will not sacrifice that for convenience. I was reviewing with the team, some of the market research, and I’ll just give you a couple of examples. A caregiver said, weekly or oral would need to be within 5% or less the efficacy of VOXZOGO, where I wouldn’t consider it. Safety is an absolute and the physician said, my number one priority for novel therapy is safety and efficacy that won’t be sacrificed for something more convenient. So whilst we believe with BMN 333, we’re excited about it. the TPP for that is for it to be at least as effective and safe as VOXZOGO with the potential for, as Hank mentioned, more convenient dosing.
But we believe that VOXZOGO is well set up to be a very robust competitor to any potential new entrants.
Paul Matteis: Thank you.
Operator: Our next question comes from Mohit Bansal at Wells Fargo.
Mohit Bansal: Great. Thanks for taking my question. And staying on the competitive theme, I think one of your competitor is also testing a longer acting CNP in combination with growth hormones in achondroplasia. How do you think about the rationale there and do you think you could do something like something similar for VOXZOGO? And then the related question is, in the ISS trial that has been posted, it seems like you are testing against growth hormones. Is there a rationale to test it in combination with growth hormones as well in that indication? Thank you.
Henry Fuchs: Yeah, Mohit. The efficacy of VOXZOGO in achondroplasia restores growth to a fairly physiologic level, over 90% of average stature growth. So it’s hard to beat that in terms of efficacy. And so a little tough to rationalize combination therapy to do better than basically normal. I think the most important thing to be doing with VOXZOGO as regards to improving long-term outcomes is to start therapy earlier, which was why we were so keen to have label extension into almost every market in the world where VOXZOGO is available to almost from infancy because that’s where you can make a big difference in the overall outcome. And again, probably doesn’t necessarily warrant the addition of another therapy, it warrants starting therapy as soon as the condition is understood.
And I think same story for ISS, we need to look at the data that comes out next month from Dr. Dauber to gauge how much of a stature of improvement we get and whether there is any room for improvement, but I wouldn’t anticipate that being a key consideration. Finally, in the Phase II study you mentioned, the inclusion of the growth hormone arm is really purely for internal reference so that we have a sense of through randomization, what the sort of apples-to-apples comparison might be. As Alexander just mentioned and I believe I steered us in the direction of, we do have agreement from the Food and Drug Administration on some really cardinally — cardinal important points of the design of the Phase III program, just to recapitulate them. We’ve agreed on the target patient population that is growth hormone naive.
We’ve agreed on the endpoint, 52 weeks annualized growth velocity as improvement. And most importantly, we’ve agreed with the agency that placebo can be an appropriate comparator for the registration. So we’re well underway. We don’t believe that we need to add other therapies into the armamentarium to augment the effect of vosoritide because it’s doing just fine by itself.
Mohit Bansal: Helpful. Thank you.
Operator: We’ll go next to Vikram Purohit at Morgan Stanley.
Vikram Purohit: Hi. Good afternoon. Thanks for taking our question. So we had a follow-up on ROCTAVIAN. So you obviously discussed some of the reimbursement and market access challenges. The product is seen here to date. But looking forward, could you speak about some of the strategies you’re putting in place now to help with the — I guess, the operational lift of the franchise? And how many months or quarters would you expect it to take for some of the challenges to be a bit less of a variable in the product trajectory, assuming the franchise stays in health with BioMarin?
Jeffrey Ajer: Hi. Thank you for the question. This is Jeff. I’ll field that one. As Alexander mentioned earlier, we’re really focused on patient pull-through in the markets where we have reimbursement approvals. So a reminder, that’s the U.S., Germany, and Italy. Patient pull-through is really the last mile, but we’ve experienced the challenges with. So we think that establishing proof of concept in pulling those patients through that last mile and getting them treated is what we need to do on a going-forward basis. How long that will take undetermined. Alexander already mentioned that at Investor Day early September, criteria will be laid out for what that looks like. And the other thing I would comment on is, in Europe, in most cases, the commercialization starts with the price and reimbursement approval.
We got the GBA approval listed in December of last year, four months ago. In Italy, that was three months ago. So one way of looking at the situation, at least in Europe, as I say, perhaps the clock started ticking three to four months ago in those two target markets and – so thinking about how long that might take during the course of this year could be instructive. Thank you.
Vikram Purohit: Thank you.
Operator: We’ll move next to Tim Lugo at William Blair.
Lachlan Hanbury-Brown: Hey, guys. This is Lachlan on for Tim. Thanks for taking the question. So you’ve identified VOXZOGO as a strategic priority and have obviously made a lot of progress on the development front in new indications. But is there anything you’re doing on the commercial front there, too? Because I noticed you obviously added a much larger number of patients this quarter than last quarter. So I was curious if that’s sort of a result of any direct initiatives or actions you’ve taken or just the maturing markets and increasing supply.
Alexander Hardy: Yeah. We’re very — thanks very much for the question. We’re really happy with the progress on books. I mean it is one of the priorities we set out we described has tremendous potential in achondroplasia, as we talked about extensively in other diseases. So right now, it’s in achondroplasia, and that ramp is accelerated if we added 500 patients in the first quarter compared to adding 300 patients in the fourth quarter of last year. So we’re seeing that growth actually accelerating. This is driven very much by the zero to five [indiscernible] to use the product from birth, which is now in many, many geographies around the world. And it’s good to see that, that growth is actually consistent across the major markets.
the U.S. actually driving the most growth, which is great to see because this is where we didn’t have the same ramp. We’re now seeing that. And I think the zero to five and the team is really focused on that as well as the other things that we’ve been doing, we’re seeing bearing fruit, which is really focusing on the pediatric and neurologists making sure we’ve got referral pathways, the setting up the skeletal dysplasia clinics, which are going to be very important, not just for achondroplasia, but also for the subsequent indications. So the team is really driving on all cylinders in more geographies. It’s one thing that actually I do want to say, which is, with regard to supply, we mentioned in our prepared remarks that we will be hitting supply levels, which we’ll be able to meet demand in the middle of this year, but we have really good news to share with regard to the maximum supply available this year.
So in January at the JPMorgan conference, we shared our supply plan for VOXZOGO, which is obviously very, very critical, especially as we accelerate our life cycle funds and ambitions for this product. We are now going to be able to supply by the end of this year, 8,000 patients, supplies work of VOXZOGO. If you remember from January, that’s what we said that we would achieve by the end of 2025. So the team here in manufacturing has moved us up by one year, and this continues to give us confidence that even as we ramp up demand for VOXZOGO, by the end of this year, we’re going to be able to meet that demand.
Operator: And that is all the time we have for Q&A today. I will turn it back to Alexander Hardy.
Alexander Hardy: Well, thank you all for joining us today. I hope you’ve heard and it came across that how hard this team and all the teams across BioMarin are working right now to shape the future corporate and R&D strategy for BioMarin. We’re setting very ambitious long-term financial targets, and we’re starting to deliver on them. We’ve got a real sense of urgency. I think that comes across. And we’re really looking forward to sharing our vision with you, and our full plans with you all in New York Investor Day on September 4. Meantime, thank you very much for your attention. I wish you all a wonderful evening. Take care.
Operator: And that does conclude today’s conference call. Again, thank you for your participation. You may now disconnect.
