Many of the physicians that are in COEs were part of our clinical trials, knew the drugs, have, you know, while they don't have the majority of the patients, they have the highest density of patients in their practices. As you'd suspect, our penetration in the COE practices in terms of new patients initiating therapy on DAYBUE was very strong. Today we have, you know, or you know, approaching 60% market share of patients that are in COEs that have initiated therapy. In the community setting, which is the bigger bucket of patients, we have less penetration, and our penetration is more in the 20+% in that setting. That's where the opportunity is at this stage in the lifecycle of the medicine. What we've done to try to penetrate that further is we increased our field footprint in the second quarter of this year.
Those people were in place in the May-June timeframe. It takes about 3 to 6 months for that to start to see fruits from that investment. Our expectation is we'll see some of that starting this quarter. The bulk of the kind of, you know, expected uptake in new patient starts and deeper reach into the community setting will come in the fourth quarter. Even in the second quarter of this year, 70% of our new scripts were from the community. Even initiatives that we put in place before the increase in the field, of course, is targeting those patients in the community setting, and those efforts are starting to bear fruit.
Right. When we speak to our KOLs, they're generally quite positive about DAYBUE. A couple of them remarked that the adoption might be higher among the new patients. Have you seen this trend, or what does that imply?
When new patients, you mean younger patients?
Yes.
Yeah. We've since launched, we have patients across all ages. Our label is for any patient aged two and above. What we've seen since launch is patients in all age brackets are using DAYBUE. As we expected and kind of what your KOL contacts are telling you, the decision maker primarily for a patient initiating on DAYBUE is a caregiver. The more motivated caregivers tend to be parents of younger children. Right. If one of us unfortunately had Rett syndrome and we were living in a long-term care facility or something like that, and our parents may or may not be part of our care continuum at this point in time, the motivation is less there. The diagnosis rate is also less because many of these older patients were diagnosed many years ago with some form of autism or something like that.
There may not be the knowledge that the patient actually has Rett syndrome and that DAYBUE is available. Obviously, we're working to broaden our education. It takes many years to get to peak penetration on a medicine. Those are some of the themes that, when you take a step back and think about it, it's logical that it's going to skew towards the younger patients, but it's not exclusive to young patients that we're serving.
Got it. Let's move to what you mentioned about the potential EU launch. If you can give some more colors, what's the focus with the launch strategy at EU in 2026?
Yeah. We filed earlier this year with the European Medicines Agency for approval for DAYBUE in Europe. We're going through the regulatory process now. We have our 120-day questions, which is one of the steps in the typical part of that process. We're answering those questions. They're amongst the questions that we would expect. Every regulatory agency has its own specifics that it looks into, and so we're dealing with that with the European Medicines Agency. The approval timeline is first quarter of next year. Once we do that, we'll start to have pricing discussions with key geographies. Germany will be the first country that we expect to launch in, and the pricing timeline for that is more towards the end of next year, assuming approval in the first quarter of next year. In the interim, we have great interest.
We have a number of partners that we're dealing with for named patient access in geographies outside the U.S., and those have all been put in place. Three partners covering Europe, one covering Israel, one covering kind of non-Asia, rest of the world, and we're starting to get interest from those. Many of those countries have innovation funds that can support a limited number of patients that generally pay for the drug at U.S. WAC. Some programs in some countries, it's free access.
Got it. Great. You know, one thing which our KOLs were quite positive about was Acadia Connect. You know, was the program based on the NUPLAZID's success, or can Acadia Connect, you know, can this model be replicated in other pipelines?
Yeah, absolutely. I mean, I don't get a lot of questions on this, so thank you for that. Yeah, no, we, Acadia Connect is our patient service hub, and it helps patients who are initiating therapy and getting through insurance reimbursement, and answering any questions that a caregiver may have that we may not be answering with our family access managers. It also helps them with their refills and maintaining therapy. That's kind of a white glove service that we're able to offer these patients. We started it with NUPLAZID. We've added it to DAYBUE, and it's scalable for new assets that we would launch that come through the pipeline.
All right. Very nice. Let's now turn to NUPLAZID. What's driving the recent, you know, the sales growth momentum in NUPLAZID?
Yeah. We've renewed investment in NUPLAZID. About a year ago, we started an unbranded disease awareness campaign that we partnered with Ryan Reynolds for to talk about Parkinson’s disease psychosis. In addition to that, we've run a more traditional branded direct-to-consumer campaign to talk about NUPLAZID and to have people, patients and caregivers, ask their physician about NUPLAZID and whether it may be the right treatment for them. Those efforts were done because coming out of COVID, this is an elderly and frail patient population. Unfortunately, there was high mortality during the COVID period in this patient population. From a business standpoint, it's kind of hard to link these two together. We did pull back our direct-to-consumer investments that we had done previously because the ROI thresholds were not being met during that time period. What happened was, awareness went down significantly.
It also just proves in the reverse that these investments are worthwhile. With low awareness amongst caregivers and patients, but a high willingness to prescribe among target physicians, it was an opportune time to reignite investment, which is what we've done. That's the primary reason, amongst other things, that are driving growth in NUPLAZID. I think the metric that we used on our second quarter call where we didn't have the DTC efforts a year ago, we had 17% year-over-year growth in new referrals for NUPLAZID. That's a testimony to the success of the campaign.
Got it. One of the persistent questions, again, quarter over quarter, has been the IRA and the pricing changes. How do you envision IRA leading to pricing pressure going forward?
I think there are two, there are a number of things in that. I think maybe the investor focus may be on the out years of when potentially, NUPLAZID would be subject to negotiation under the IRA. Maybe I'll just stick to that for simplicity purposes. NUPLAZID, because of the age profile of the patient population, is, you know, call it a 70+% Medicare patient population. With that, we're subject to kind of oversight by the, or, you know, influences by the Inflation Reduction Act. Today, there are benefits of being a small company as part of that act, which actually gave us net price benefit in this year.
If you look out, and we'll say, if we look at the list of medicines and where we, you know, some of the overlays of protections for small companies, 2029 would be the first year that NUPLAZID would be eligible for negotiation under the IRA. That's the time period that we point investors to. That is probably a good assumption on when negotiation would happen. If they fix the pill penalty between the nine and 13 years, that can extend another year without negotiation for NUPLAZID just due to the launch year of NUPLAZID in 2016.
That's a time period where I would say between now and then you can think about, while we don't foreshadow pricing, you know, think about inflation, a little less than inflation is probably the net price benefit that NUPLAZID would have because we're benefiting from this small company provision that generally unwinds between now and the time of negotiation. Then there'll be a step down in net price once we get to negotiation. There's the first two years, there are bounds within the legislation that limit the amounts of price deduction that can happen. After that, it's more open. There's no comp yet to NUPLAZID. NUPLAZID is the only approved medicine in its indication. The drugs that have gone through negotiation already have all been in competitive markets, where they've offered discounting and there were disconnects between Medicare and the commercial setting. That dynamic doesn't exist in NUPLAZID.
We'd have to see some other medicines that are like NUPLAZID go through the negotiation first to get more of a flavor of how big or small the impact may or may not be once we get there.
Got it. Very helpful. Maybe this is the right time where we can move into some of the pipeline updates. You know, we have been getting a couple of inbounds on the PWS. Let's start with 101.
Yeah.
For ACP-101 in Prader-Willi syndrome, what trial outcomes would most convince physicians to prescribe it given the current competitive landscape?
Yeah, I think for us, what we're hoping for is to replicate. There was a previous phase 3 trial that the predecessor company for ACP-101, Levotherapeutics, which we acquired a couple of years ago, ran with two doses. One of the doses in that trial was the 3.2 milligram dose, which is the only dose we're exploring in our current phase 3 trial. If we're able to replicate the data and the P-value of the 3.2 milligram dose from that previous trial, we'd be very pleased with that. We think that would support a strong regulatory package and will be clinically meaningful and will have us have a competitive label in the future market for hyperphagia for patients with Prader-Willi syndrome.
Got it. For ACP-204 in, you know, Alzheimer’s disease psychosis, how do you view Bristol's competing program? Do you prefer being first or following an established entrant?
Maybe I'll just step back and not comment publicly on other people's medicines, but I would certainly say clearly we follow the competitive landscape for all of our medicines. I think for us, maybe I'll answer the question a little bit, take it a little different. What we don't want to be in any of our medicines is like the fifth to market with an undifferentiated product, just trying to eke out a small market share. That's not our business model. What we're looking to there, I think ideally, what you'd like to be is first to market with the best TPP and possibly only therapy on market for a while. Yes, but that doesn't always happen. For us, what we're looking to do is continue to invest in our medicines, and we know there are strong competitors out there and other very smart people.
If we can bring differentiated therapies to market, and whether or not we're first in the initial wave or later with something much better, we feel that we're well positioned to compete and be successful as a company and serve patients in any of those scenarios.
Got it. Across your pipeline, which programs currently excite you most from a commercial perspective and why? How are you prioritizing investment across the pipeline?
I think on the investment side, I think we're in a fortunate position where we're not picking and we're not picking to invest in one asset and not in another because of financial constraints or certain metrics. We don't run the company or R&D as a % of sales. We're still kind of an emerging and growing biotech company. Where we look from a financial perspective is, and we're disciplined, if the data is strong, we'll lean in and aggressively invest to the next milestone. Whether or not that's an internal program or bringing in programs from the external environment through business development, if the data is not there, we'll be honest with ourselves that it's not there and we'll stop investing. We've done that historically across the pipeline. That's kind of how we look at it.
From a financial capacity standpoint, we have the ability to invest more than we have today. It's not like if we bring something else in, we need to cut something else to make room for it. There's room to broaden the pipeline and invest more. For me, as CFO of the company, what excites me most about the pipeline is just the breadth of it in its entirety, not necessarily one thing. I think as we released on R&D day, while not all the medicines will come, those that we disclosed altogether have a peak sales opportunity of approximately $12 billion. That's exciting to me as CFO. We'll continue, as I mentioned at the earlier part of this question, to invest in the assets that are promising and continue to be promising. We'll see what comes out of it. Overall, it's exciting.
Great. That brings us to the last question, which is kind of related to the previous question, which is, how is Acadia Pharmaceuticals thinking about external innovation? What are the key criteria when you are looking at screening some of those technologies or vetting some of the outside technologies?
Sure. I started, right? We have the neurological side of our business, at least the commercial side today, which is NUPLAZID for PDP. We have the rare disease side of our business, commercially today, that's DAYBUE for Rett syndrome. Our pipeline falls in both of those sides. From an external innovation business development standpoint, we continue to want to invest in both of those, and ideally, we would bring in things that are in the clinic, because that's something that is more near-term focused for us, more near-term focused for investors. We also bring earlier stage assets because the actionability on those is easier. If we can bring some early stage assets, they can be the late stage assets of tomorrow. That's how we think about it.
I think we also will close with, I like to say, kind of a forced sense of urgency on business development so we can be disciplined and do the right deals at the right time. We're not, you know, we don't have a near-term patent cliff and all of a sudden have to do a bet-the-company deal because you have to do something. If we have that forced sense of urgency today, we'll avoid the necessary evil of doing something big later because you're forced to do something.
Great. Thanks very much, Mark.
Thank you.
I thought we kind of covered generally the most important aspects of Acadia Pharmaceuticals. Thanks for all the insights.
All right. I appreciate it. Thanks for the time.