So do you think that the pemphigus results from rituximab where there was about a 30 percentage point placebo benefit is a relevant confer? Or is a smaller benefit than that still competitive? How should we think about that please?
Tim Van Hauwermeiren: James, thank you for being with us today. And thank you for your pemphigus questions. Certainly an exciting indication and a very ambitious trial design. There is no delay in the pemphigus study. Remember, when the study is fully enrolled, there is a substantial amount of time involved in follow-up of the patients. So we’re assessing whether we can push patients into CRM within a 30-weeks times period, and then actually the roll over into the open label extension study where we continue to collect data, which will be important for a top line data readouts. In terms of comparing to the pemphigus trial, I would strongly advise against it. I mean, these are molecules with totally different modes of action.
And therefore the trial designs are totally different. The pemphigus endpoint was taken at a totally different time point. It has its own particular steroid tapering protocol in the background, we work with ours, which is specific. So I would not really compare the two. It’s a totally different situation. What we’re looking for, for such a stringent endpoints, CRM in for at least 8-weeks within a 30-weeks’ timeframe. That’s unattainable for addiction by the way, is a statistically meaningful separation between active and placebo. That is basically the definition of the endpoint, the primary endpoint. And then in the secondary endpoints, we will unpack the clinical utility of the drug in more detail by looking at the speed to disease control, the amount of stereo tapering we can achieve.
We will also look at the pemphigus fallacious patients, which is a subset of the study. And we’re also going to look whether we can actually push people into complete remission of therapy as portion of the open label extension study. So very exciting, very bold endpoints, which could be present a game changer in the pemphigus space. Thanks for the question.
Operator: Your next question comes from a line of Akash Tewari from Jefferies. Your line is open.
Amy Li: Hi, this is Amy on Akash. Thanks so much for taking our question. So one on PV. How do you expect the more severe patients in Phase 3 to impact FcRn? Additionally, do you need the cell drop to have sustained remission? Or do you consider this as more of a bridge to rituximab? Thanks so much.
Tim Van Hauwermeiren: Thank you for these two excellent questions. So first of all, we do not see any difference between moderate and more severe patients in the ability to respond to the VYVGART. Remember, we had both on trial in Phase 2, it’s true that in Phase 3, we’re recording a somewhat more severe patient population, but we had them in Phase 2. And they have an equal right, to respond equally fast and equally deep and equally durable to VYVGART as the milder patients. So that there’s no, real differentiation there. In terms of positioning of the product, and you’re correct in calling out that maybe we can go faster to steroid tapering, which is something which patients badly want and need. You cannot continue these patients on a high dose of steroids for too long period of time.
And then of course, we had this beautiful publication, where we started to unravel the biology behind the durable clinical responses, which we have seen in Phase 2, as we tried to set in the prepared notes. FcRn is much more than just you know receptor involved in IVIG homeostasis, it is also involved in all the antigen presentation. And actually, we see not only and sustained reduction in auto antibodies, but also a sustained reduction in auto attractive B cells in our perfect suspicions, which basically means that – is disease modifying and has the ability to either postpone or replace completely and rituximab. Thank you for the question.
Operator: Your next question comes from a line of Danielle Brill from Raymond James. Your line is open.
Danielle Brill: Hi, guys. Good morning. Thanks for the question. I also have a question on PV. Sort of a follow-up on to a prior question. I’m curious what endpoints you think will dictate [escolares] rank and the treatment algorithm? Specifically, and what do you think it needs to show to leapfrog with rituximab? And then how should we think about potential recruits to BP? Thank you.
Tim Van Hauwermeiren: Thank you, Danielle, for the questions. Of course, we have to be careful, hit and wait for the Phase 3 data, because they will ultimately dictate whether we have a drug induced indication, and how to position VYVGART within the pemphigus treatment paradigm. We did extensive work with the community, both physicians and patients, actually the entire global physician community is surrounding this trial. And of course, we have been doing extensive work with the patient advocacy group, what patients badly need is a fast response. They want to see stopping the formation of lesions, closing of lesions as fast as possible. They also want to taper steroids as fast as they can they hate steroids, steroids with a passion.
So imagine we can repeat the Phase 2 data in terms of quick onset of action. Remember, 90% of patients in Phase 2 went into disease control within the first, two weeks’ time. And then we can keep them you know, in a very low disease activity, state of complete remission, whilst taping the steroids. I think that will position and VYVGART very well for positioning in the pemphigus treatment paradigm. But let’s not get ahead of ourselves and wait for these data. Thank you
Operator: Your next question comes from the line of Yaron Werber from TD Cowen. Your line is open.
Yaron Werber: Great. Thanks for including me and congrats on another great quarter. So a quick – also questions from me for the ADDRESS study. So the studies including both naive and experienced patients, and if you look again at the rituximab studies, the placebo vary between a 10% and a 28% response rate. I think a lot of the Kay wells are kind of talking about a 30% to 40% delta. That was easily achieved. So if you look at your CRA from the Phase 2 sort of the seven out of 10 at the optimal dosing. Can you give us a sense sort of in this study, the placebo? Is that 10% to 28% relevant at all or do you think it’s going to be even lower? Just given the tightness of the endpoint? And are you expecting sort of 50/50 in terms of naive and experience in the study? Thank you.
