And of course, that’s where the subcu formulation also becomes important. Because if we are thinking of people staying on drug for longer, and I’m certainly not suggesting 25 years, but this could be a much longer period, certainly than the 18 months, and therefore the convenience of a subcu formulation is even more important. So we are learning every day. I think we saw that at CTAD. We understand increasingly the importance of early treatment. We’re seeing the importance of staying or the benefit of potentially staying on treatment. And so, that has all kinds of commercial implications and how we do more studies and develop different formulations. And it’s actually quite exciting.
Operator: We’re next going to Umer Raffat from Evercore.
Umer Raffat: I wanted to focus on lecanemab subcu. And, Priya, I think you mentioned two things. One that there’s a subcu maintenance filing, which is separate, which could be in 2025. Could you confirm if the dose is lower if it’s a single shot instead of two? And also, the FDA interactions on subcu that you mentioned, are they a follow up to previously agreed upon trial design for subcu? Or do you think you need clarity whether plaque reduction alone will suffice for filing?
Priya Singhal: First of all, I think on the maintenance subcu, that is really a much later potential evaluation and filing. So I won’t be able to comment further on that, specifically with regards to dose because we first need to evaluate IV maintenance and that is really the next milestone that’s on the docket here. And then going back to your other question of what is the purpose of the FDA regulatory meeting, so maybe just stepping back, Eisai has had a number of meetings with FDA prior to the launch of the subcutaneous open label extension sub study that I spoke about and from CLARITY AD. And so, what we do know is that we do need to show bioequivalence on both PK and then we need to show comparability on plaque reduction.
And based on the six month data that we just shared, and Eisai spoke to at CTAD, we believe we have achieved that. And so that’s the first part. The second part is with that – because we have an 11% increase with overall AUC, area under the curve, exposure and 14% increased plaque removal, at the six month time point, does that result in a different dose? I think that that is really a matter of discussion, and we would have to discuss that with the FDA. So can’t really comment more on that. But most importantly, I think the goal here was to show bioequivalence, which we believe we have achieved.
Operator: And next we’ll go to Michael Yee with Jefferies.
Michael Yee: I wanted to come back to a topic on the AHEAD 3-45 study. I believe that your partner, Eisai, commented there could be an interim analysis based on 400 patients and biomarkers. I notice that it’s been enrolling for a while, but maybe it just sort of is picking up steam. Can you just maybe talk a little bit about the progress of that study, how you see that study and the status of patients getting in?
Priya Singhal: What I can tell you is that it’s a very important part – the AHEAD 3-45 study is a very important part of the overall development plan for LEQEMBI as an anti-amyloid agent. And the reason for that, I think Chris mentioned it as well just a few minutes ago, that we know that plaque builds up – amyloid plaque builds up for many years. And then there’s sort of a shift where tau tangles start appearing. And then you have the appearance of symptoms. So, over the last several years, there’s been a lot of work on clinical staging and such. And we know that the anti-amyloid agents that are currently like – just like LEQEMBI, which is really the only one with traditional approval, is targeting mild cognitive impairment – patients with mild cognitive impairment as well as mild dementia.
But these patients already have symptoms and potentially a burden of doubt. The purpose of AHEAD 3-45 is to look at different levels of amyloid plaque in patients who do not have symptoms, and see whether the addition of an anti-amyloid agent like LEQEMBI can alter the costs of disease. So that’s really the overarching aim of a study like AHEAD 3-45. It’s a very large study. As you can imagine, it’s hard to find the patients. But we are very pleased with the progress that the study is making. And as Eisai commented very recently, there is the potential to do an interim analysis and think about whether other regulatory pathways are open with interim data. But we haven’t really commented beyond that. These remain possibilities, but I think it will depend on how well we do with the recruitment and what the goals of eventual patient access are.
Operator: And next, we’ll go to Terence Flynn with Morgan Stanley.
Terence Flynn: Just a two part for me. Just was wondering if you can provide any more detail on the breadth of prescribing for LEQEMBI? I know you give us the 800 patient number. But if you look at how many centers that’s across, that would be helpful. And then I know you made some comments on some progress on the MAC coverage. Any more details on the timelines there for when we might get broader coverage at the MAC level? I know there’s a couple of MACs already covering, but anything there would be helpful. Thank you.
Christopher Viehbacher: Terence, I don’t have any real update on the MACs. There’s, I think, what, a dozen of them and they’re at various stages. I think by the time that’s more – that most of them have got there, I think there’s an assumption that that takes anywhere from 60 to 90 days to get through. So towards the end of the year. On coverage, it’s one of the most interesting things is really just the diversity of situations that we see. I talked to some physicians in some major medical centers. They’ve got the protocol, they’ve got the treatments, they’re putting patients through on a regular basis. But I’ve been talking to some major medical centers. You might think they’ve got this all handled, and they’re still thinking about these protocols.
And it’s protocols around what’s the right profile of the patient to put in this. There is a teamwork approach on this. And so, people have to connect on that. For some of the IDMs, they have all of the elements, but they have to connect internally with their MRI centers with the infusion centers. So it’s a little hard to give you a broad brush. I would say, every day, we are finding more and more patients, obviously, getting through the course. We are looking upstream at a number of indicators because really revenue is a lagging indicator between – even when we start looking at registry results, it’s somewhere between four to six weeks before we actually see those patients going on drug. But some of those timelines are changing constantly.
So it’s a pretty moving process here. It’s just – every day changes. That’s where, at some point, we get enough momentum, we get enough of these barriers cleared. One of the biggest is still the getting an appointment with a neurologist. And that’s where I think we’re looking at what can we do with blood based biomarkers, which are now available not obviously to replace PET scans or MRIs, but can we use them to triage patients, so that those who actually get into a neurology clinic are the ones who are already eligible. So there’s an awful lot of thinking right on the fly as we learn from this experience. Again, this is really one where there’s – there aren’t really great analogs. I know some people try to suggest the CAR T approach. And while that is also a product in a process, the volumes – the scale of this is much different.
And we’re not obviously anywhere near as complex as a CAR T approach. So for us, there’s not really any analogues we can do. And so, we’re learning on the fly as we go along. But like I say, every day brings progress. And all of the indicators are in green so far, and it is really just getting enough critical mass now of all the centers who’ve got these care networks and care pathways in place.
