Ash Verma: I had two. So for DAYBUE, I know in prior instances you have actually self-guided the sales for subsequent quarters. At this time, I think you just left it at sequential growth. Is there any reason for that? If anything, you sound very confident on the rebounds. I was just curious what sort of driving that dynamic. And then, secondly, I wanted to ask about your cost structure. Like have you considered revisiting that. I mean, compared to last year, this year we’ve seen new positive, negative symptoms not working out favorably and the DAYBUE persistency coming in below, I’m guessing where you would have originally assumed. Does that make you rethink where your cost structure is? Thanks.
Steve Davis: Yes. Thanks much, Ash, for the questions. Mark, I’ll let you take both of them.
Mark Schneyer: Yes. Sure, sure. On the guidance, as we transition to annual guidance, you’re no longer to give the kind of one quarter forward guidance. I guess the unique thing about the first quarter of this year is that we were expecting a sequential down quarter. So we thought it was just helpful in giving the full financial expectations for the year to give the first quarter guidance for this year as well as annual guidance. We don’t expect to see sequential declines going forward. So we’re going to keep the annual guidance just like we do for NUPLAZID. On the cost structure, thanks for the question. As Chief Financial Officer, of course, I look at the cost structure every day. But I think as we look at what’s the right cost structure for the business and the investments that we’re making, there’s no change there.
Yes, we had unfortunately, our negative symptoms of schizophrenia trial was not positive, but we hadn’t made commercial investments in negative symptoms of schizophrenia before that readout. So there really is nothing to unwind. Our business is expanding. We’re making investments for ex-U.S. for DAYBUE that didn’t exist last year. So that’s kind of a new leg to the business that requires investment. And we’re still investing appropriately for growth and DAYBUE in the U.S. So all of that together leads us to supporting the investments that we’re making. But as we’ve done, over the last couple of years in NUPLAZID, right, we’ve looked at that franchise of making efficiencies and we look to make the right investments as additional investments or reduction investments across our entire cost structure on an ongoing basis.
Operator: Thank you. One moment for our next question, please. And it comes from the line of Marc Goodman with Leerink.
Marc Goodman: Yes. My question is around the Prader-Willi trial, and I’m curious if GLP-1 uptake has been hindering enrollment and just the general thoughts around how GLP-1s will play into potentially not needing as much therapy for Prader-Willi and the eating disorder there. And then, secondly, can you just give us a sense of how many patients are on NUPLAZID these days? We haven’t talked about it yet. Thanks.
Steve Davis: Yes. Thanks much, Marc, for the question. I’ll take the first one. So in Prader-Willi, we’ve seen no impact at all of GLP-1 utilization. In fact, as Kimberly mentioned, we have a very enthusiastic patient population and medical community, and the enrollment is moving very well. We’re enrolling ahead of plan. So we haven’t seen any impact of GLP-1 or anything else, honestly. I’m sorry, second question. Brendan, you want to take that on NUPLAZID?
Brendan Teehan: Yes, sure. Thanks for the question, Marc. We’re continuing to see increases in patients on therapy on a quarterly basis. So between the community and LTC in long-term care, obviously, we have great visibility into the community. And so we’ve added patients in the first quarter over the fourth quarter on the order of about 8,500 in total patients. And then in LTC, that’s obviously more like a quarter of our business, but you know that prescriptions are often split between patients. So we don’t have absolute visibility into the number in long-term care.
Operator: Thank you. One moment for our next question, please. And it’s from Sumanth Kulkarni with Canaccord Genuity. Please proceed.
Sumanth Kulkarni: On DAYBUE discontinuations, is there a sweet spot in terms of months on drug where discontinuations tend to cluster, and if a patient remains on drug after that, they tend to do so more easily after they pass that point? And are most discontinuations confirmed by clinical visits, or are there patients that have gone greater than 60 days without a refill?
Steve Davis: Thanks much. I’ll answer the first part. Brendan, I’ll ask you to answer the second part in terms of the split on discontinuations. So Sumanth, we do see, we touched on this on the call, so let me just expand out a little bit. We do see more discontinuations in the first two fills of drugs. So there’s a disproportionate number of discontinuations there. Now, some of that you would expect. We see this pretty routinely with drugs that have subjective endpoints. We see it all the time in neuropsychiatry. We have a steeper level of discontinuations in the first two to three months. So we do see some of that. We do feel, however, though, as we parse through that data, that given the level of titration that we’re seeing across the brand, and just recognizing that it takes longer than to get to therapeutic levels, that we do think that some patients are discontinuing prematurely before they have an opportunity to see those benefits.
And there’s an opportunity for us there to improve on that, and it’s a high area of focus for us to now, and as Brendan discussed on the call, particularly around educating caregivers and medical professionals around their expectations around time, setting the right expectations about time to get to benefits, and then managing to that is a very important area of focus for us. Brendan, do you want to take the other question?
Brendan Teehan: Yes. So Steve obviously did a great job of kind of articulating where we are with when discontinuations take place, and it’s probably intuitive, but the further out we get in fills, the flatter the curve gets, right? There are fewer and fewer patients that are discontinuing when you get beyond four and five fills with DAYBUE. And I think we’re encouraged by that on two levels. Number one is obviously our fams are very close with these families. We have weekly conversations with them, so we have good confidence that once they get through that early part of that patient journey and tolerability, GI management strategies, we do a nice job of keeping them on therapy. And we also know from talking to Centers of Excellence how often they’re seeing these patients.
Many of the physicians want to see their patients regularly after they start. The vast majority of them, I think, want to see patients at the month three time period, partially because that’s the length of the clinical trial, partially because some payers are asking for that information at that point. And then I think they make judgment calls on how well the patient is doing, how often they want to see them after that. But with persistency rates now out to nine months in what we’re seeing, I think we feel confident in what we’re seeing in terms of patients being able to start and stay on therapy after they get through the early part of the treatment journey.
Mark Schneyer: I think I’ll just add one thing to that. I think the question was also, do we — or more discontinuations happened because they’re confirmed versus going over 60 days? And I think you asked it in the clinical decision. I think for us with the connectivity we have with our fams, we do find for the data we received, the majority of discontinuations are confirmed discontinuations. And it’s the minority of discontinuations that are deemed discontinued for greater than 60 days, many of which of those then subsequently become confirmed when spoken to the caregiver.
Operator: Thank you. And we have one moment for one more question. One moment, please. And it comes from the line of Uy Ear with Mizuho. Please proceed.
Uy Ear: Yes, just a question on NUPLAZID. So you indicated that real-world evidence has sort of grown, a new start. I’m just wondering like, what exactly is it? Is there anything that’s changed in practice? Are patients, I don’t know, less scared to come back into the physician’s office? Or is there anything fundamentally in the physician’s office in the long-term care that is perhaps increasing the number of patients? And secondly, would you consider perhaps increasing your investment to drive further growth? Thanks.
Steve Davis: Thanks much for the question. Brendan, you want to take the first question?
Brendan Teehan: For sure. So I think there are a couple of dynamics. If you’ll recall, carbidopa-levodopa scripts in the peak of the pandemic and even towards the end were declining over time. And declining would suggest fewer Parkinson’s disease patients overall. Even today, we’d say that’s flat. So I wouldn’t call that a rebound by any stretch of the imagination. I would call that stability. But I think also easing safety measures that have patients returning to clinics and hospitals are certainly giving us more shots on goal for NUPLAZID as the choice for PDP. I think that combined with real-world evidence has given us a very compelling story on why we should be the first and best choice and has given us an opportunity to grow share.
And what we’ve seen in long-term care, I think, has been pretty logical in terms of resident counts in long-term care facilities. They obviously plummeted during the pandemic. Towards the latter part, they have increased. They have continued to increase, but NUPLAZID’s performance has outpaced both the resident counts and APs in that space.
Steve Davis: I’ll take the second part of that. So as Brendan mentioned, when we look at metrics like carbidopa-levodopa, it looks like the overall PDP market is relatively steady or flat, but we are seeing growth with NUPLAZID there. And I think that’s the genesis of your question. So would we consider increasing our investment? And I think the answer is, we do monitor that too on a day-to-day, week-to-week basis. We look for opportunity. We’re constantly assessing, is this the right level of investment given the opportunity? And as we’ve said before, if we feel like there’s opportunities to produce an appropriate ROI, we may make those investments. But at this juncture, that’s just a key element of our overall objective of optimizing cash flow.
Operator: Thank you. And with that, I will conclude our Q&A session and pass it back to Steve Davis for final comments.
Steve Davis: Thank you, operator. Thanks again, everyone, for joining us today. We look forward to updating you on our progress next quarter.
Operator: And with that, we thank you all for participating, and you may now disconnect.
