Emil Kakkis: Well, I think you’re hitting on a really important thing. Let’s talk about what the FDA asked for. They wanted to have the major clinical fractures, excluding fingers toes and skull as the endpoint because they feel those are the most clinically meaningful. However, whatever they think is one thing they’re dealing in fractures from osteoporosis. The truth is what you talked about is really important that the vertebral fractures and other types of fractures that would develop in deformation of the bone are actually things that drive very poor outcomes. So our trial which will have pediatrics and also has a very young group patients — we’ll look at not just clinical fractions but also for cerebral fractures and other fractures which we think will benefit.
So I think we’ll be able to show the clinical fractures and hit the FDA’s required endpoint, but we hope to be able to expand that to talk about other aspects of the disease, particularly in the very young patients in the COSMIC study and to be able to show how support for their vertebral bone would not result in the kind of degeneration degradation that leads them all to be wheelchair bound as five or six year old. I think that would be an amazing result. We’re going to see what we do. But based on the very substantial lumbar spine bone mineral density improvement of 20% in some of the young kids we kind of expect this line to be strong and to change the future of not deforming like they’ve had in the past. So I would say, we can prove the FDA approval but the broader acceptance of the treatment and its reimbursement will be supported by the rest of the body of data which we are including in our plan.
Michael Riad: That’s really helpful. Thank you so much for your time.
Operator: Thank you. One moment for our next questions. Our next question comes from Yigal Nochomovitz with Citi. You may proceed.
Q – Unidentified Analyst: Hi, team. This is Carly on for Yigal. Thanks for taking our question. We had one commercial question. It looks like you’re expecting a pretty significant reacceleration in revenues in the fourth quarter in order to meet the guidance range. Now you mentioned, an inventory impact to Crysvita during the third quarter. But can you talk a little bit more about your assumptions driving that acceleration in revenue that you’re expecting? Thank you.
Emil Kakkis: Sure. Let me — I’ll hand it over to Erik. The fourth quarter has a lot of differences in how things perform. There’s always a lot of lumpiness as well. But Erik, if you want to deal with what you think how revenue is going to go in the fourth quarter?
Erik Harris: Yes. I think if you look at previous years we’ve always had a strong fourth quarter. So it’s typical seasonality, which will also this year, will entail some inventory rebuilding following the NDC swap out. And as I stated earlier, demand remains very strong. In fact our demand in Scotland, is higher than it was at this point last year. So we remain confident that we’ll see a strong fourth quarter.
Emil Kakkis: Yes. I think if you go back and look you’ll see every fourth quarter has been an up quarter. So we’re on track. We feel pretty good about where we are in the business.
Q – Unidentified Analyst: Okay. Great. That’s helpful. And then maybe just one follow-up related to the Wilson program. how you’re thinking about the size of the addressable population for a gene therapy of Wilson and maybe what you’re hearing from KOLs about the proportion of patients, not well managed on chelators and on the more severe end of the disease spectrum that could be addressable? Thank you..
Emil Kakkis: Yes. I think the Wilson market potential is an important question. The 50,000 60,000 patients probably more, because it’s underdiagnosed in my view. And you can look at it as maybe the 20% of patients that aren’t well managed as the core indication. But I think with the drop out of the Alexion AZ Chelator, as a competitor and showing that just chelation is not good enough to make patients better — the door is open to the idea that improving copper distribution could make patients feel better, do better than you can get just with a chelator, which means it might not be just a 20-plus percent that have problems with their chelators — it could mean them more of a majority of the patients with Wilson. We’re encouraged that the patients are getting off their Yes, the chelators, but I think we’re also really encouraged that the copper distribution seems to be improving even at the lower doses and that patients seem to be feeling really good.
My hope is, if you restore copper distribution that — the effect of copper deficiency, which is occurring in Wilson disease overlay it on top of copper toxicity is a real factor. And if we can make people feel a lot better and perform better I actually think there’s a potential for this to be an indication that becomes the majority of patients. Because our ability to manufacture with the Pinnacle platform in our own plant keeps the costs really low it also means, we can manage the pricing in a more intelligent way that would enable a larger fraction of these patients to get put on therapy and actually build a bigger business model out of it, than one based on a $3 million a person kind of price point which I think makes it more challenging.
So we look at the opportunity here as potentially larger than the initial views, if we can make patients feel better and do better. And I think there is a real chance for that with the Wilson gene therapy.
Q – Unidentified Analyst: Great. Very helpful. Thank you.
Operator: Thank you. One moment for our next questions Our next question comes from Tazeen Ahmad with Bank of America. You may proceed.
Q – Tazeen Ahmad: Hi. Thank you so much for taking my question. Emil maybe just wanted to clarify one point. And then sorry, if it was already asked before. But when you talked to the FDA about downsizing the OI Phase 3 trial you were supposed to get specific feedback on that. Just wanted to hear your thoughts on what FDA’s view on that particular request was or if you’re still waiting to hear back. Thanks.
Emil Kakkis: Yes. We haven’t really discussed the details of going through that, but the plan on the Phase 3 with the addition of the interim assessments we think won’t be a problem. But we haven’t really disclosed any ongoing discussion with them, but we’re comfortable with the ability to get the interim set. And the size of the study is really up to us. In terms of safety the exact trial sizes well-above 100 patients is more than adequate in size. So we’ll come up with a plan with them but I’m not concerned about our ability to get that accepted.
