My name is Chris James. I'm a senior biotechnology analyst here at Ladenburg Thalmann. We're pleased to have ACADIA Pharmaceuticals. We have a buy rating on the stock. ACADIA is passionately focused on improving the lives of patients with CNS diseases. The company commercializes a drug called NUPLAZID, or pimavanserin, which is the first and only medicine approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. Speaking today, we have Steven R. Davis, ACADIA's President and Chief Executive Officer. He's a member of the board. He joined in 2014 as the Executive Vice President, Chief Financial Officer, and Chief Business Officer. He was appointed to Interim Chief Executive Officer in March of 2015, and President and Chief Executive Officer in September of 2015. I'll let Steve take it from here. Thank you.
Great. Thanks, Chris. I'm going to move over here so I've got just a few slides. As Chris mentioned, we'll spend about 15 minutes. Just to level set with everyone, I'll do a brief presentation, then we'll go to Q&A. I think everyone in the room is probably familiar with the fact that the pharmaceutical business has certain inherent risks and uncertainties. Please see a copy of our latest SEC filings for a description of these risks and uncertainties as they relate to our business. At ACADIA, we're transforming the treatment of Parkinson's disease psychosis. The basis for this, as Chris mentioned, is NUPLAZID, or pimavanserin, which represents an entirely new treatment paradigm in the treatment of PDP, or Parkinson's disease psychosis. NUPLAZID is the first and only drug approved by the FDA for hallucinations and delusions associated with PDP.
I mentioned it represents an entirely new treatment paradigm, I just want to expand on that for a second. It's the first drug approved to treat hallucinations and delusions in these patients without impairing motor function. The way that NUPLAZID achieves this is through its very novel mechanism of action. NUPLAZID is, in addition to being the first drug approved for the treatment of PDP, it's also the first selective serotonin inverse agonist approved by the FDA. It preferentially targets 5-HT2A receptors. Every other antipsychotic works through multiple mechanisms, but primarily by blocking dopamine or, in particular, the D2 receptor. There are pros and cons to blocking D2. You certainly get efficacy by blocking it, but you also get a whole host of side effects, including metabolic dysfunction, sedation, things like akathisia, et cetera.
In the case of Parkinson's patients, you have additional liabilities with blocking D2, and that is a consequence of the fact that Parkinson's, of course, involves the deterioration of the part of the brain that produces dopamine. To treat the motor symptoms of Parkinson's, we administer synthetic dopamine or dopamine agonists. When patients develop psychosis, and about half of Parkinson's patients ultimately will during the course of the disease, if you give them a dopamine blocker, that drug has the potential to block the effects of the drugs used to treat the motor symptoms. Physicians make this compromise, or they previously had to make this compromise, in terms of whether they aggressively treat the motor symptoms or the psychosis. They usually have to settle somewhere in between. With NUPLAZID, they no longer have to compromise.
They can aggressively treat the motor symptoms with dopamine agonists or drugs that are increasing dopaminergic tone. They can administer NUPLAZID, which doesn't touch dopamine, just blocks 5-HT2A, and as a consequence, have the potential to get much better outcomes for patients. I mentioned some of the downsides of blocking dopamine D2, and one of them is we avoid many of the significant safety and tolerability issues that you have with that. With our very selective serotonin inverse agonist profile, we have a very favorable tolerability profile, which is really important in this frail and elderly population. I'm going to backtrack for just a sec and just share a couple of slides regarding some of the results we achieved in clinical trials.
What's represented here is the results we achieved in our -020 Study that was the single pivotal study that served as the basis of approval for NUPLAZID. What we see here is a very significant improvement on the SAPS-PD scale from baseline. With virtually all CNS drugs, neuropsychiatric drugs, I should say, you get a placebo response, and we saw that here. What we see, beginning with week two, is a very nice separation from placebo. In addition, importantly, what we see in this next slide is not only do we see a very strong, very clinically meaningful response, we see it across the spectrum. Some patients improve, exhibited a one-point response. Some at a three-point, five, seven, 10. You can see in 14% of the cases, we established a complete response.
The thing that I want to point out here that's really important is even if a patient achieves only a one-point response, a one-point response can represent the difference between a patient having hallucinations or delusions on a daily basis versus a weekly basis. As you can imagine, many of these patients are cared for by their spouse. Many of them are in long-term care facilities. Just being able to reduce the frequency or severity, or both, of hallucinations and delusions can have a significant impact on their quality of life. We launched NUPLAZID a year ago, May 31st of this year. So May 31st of 2016.
We're now a little past a year, almost a year and a half into the launch, as I think many of you who followed our quarterly earnings reports are aware, we've had a very successful launch of the drug and getting really nice traction. We're targeting 12,000 neurologists and psychiatrists. The vast majority of our targets are neurologists. As many of you know, earlier this year, we expanded our sales force from 133 reps to approximately 155, primarily dedicated to increasing penetration in long-term care. We are now on all Medicare Part D formularies and continue to expand our coverage on commercial formularies with over 90% of commercial lives now covered. More recently in the last quarter or two, we've begun focusing on increasing awareness on the patient and caregiver side of the equation. We feel like it's very important to establish a baseline with physicians.
They need to know about the drug. They need to have a good understanding of the advantages of the drug. We're at a point now in the launch where in addition to doing that, we're beginning to increase our attention with patients and caregivers. There's a very significant under appreciation of disconnect in the minds of patients and caregivers between psychosis and Parkinson's disease. Their awareness until they actually present with those symptoms and their doctor tells them, makes the connection for them, "Yes, the psychosis, these hallucinations, and delusions you're experiencing are linked to your disease progression." The awareness otherwise is in the single digits. There's a great opportunity for us to increase awareness and thereby increase the dialogue between patients and caregivers. Because many times these patients suffer with these symptoms for a long period of time before they discuss them with their doctor.
A lot of it has to do with just the generational mindset. Many of them are concerned that now in addition to having Parkinson's disease, "I'm beginning to hallucinate. I'm seeing things that aren't there." They may not be aware of delusions, and they usually just imagine that it's just because I'm getting old, I'm getting senile. They don't associate with the disease. They don't realize that there's a treatment out there that can help them. If we could increase that dialogue, I think it'll be a great result for patients, and very important medically as well as commercially. We're doing this through a very substantial campaign to get out to events that are frequently on weekends or many times during the day for patient support groups. That's one of the big initiatives we've launched this year and early returns are very promising.
In addition, we are at all major medical meetings. We have a KOL speakers program dedicated just to patient and caregivers. We also have one, of course, dedicated to physicians, but we have a speakers bureau that is now dedicated just to these patient and caregiver programs. We have multimedia campaigns including digital and some non-digital as well. I'm going to shift gears for a second now and just go to our mid to late-stage pipeline. What's represented here is, I think the take home message is really that in addition to Parkinson's disease psychosis, we're pursuing five other indications with this drug. I'm going to speak more to those on the next slide. What we see here is, of course, we're approved in Parkinson's disease psychosis, where pimavanserin or NUPLAZID is administered as monotherapy.
We announced in the fourth quarter of last year positive results in our phase II Alzheimer's disease psychosis study. That's also a monotherapy approach. I'll speak more to each of these indications in the coming slides. We also have a phase II program ongoing in Alzheimer's disease agitation, and as we can see here, everything on this side of the slide is a monotherapy. Due to the very favorable tolerability profile of pimavanserin and its very unique pharmacology, we think there are also opportunities as adjunct therapy to improve results on top of baseline therapy. In schizophrenia, we have a large ongoing phase III study in schizophrenia patients who achieve a response, but it's an inadequate response with traditional antipsychotics. We also have a very large study ongoing in schizophrenia to treat the negative symptoms of schizophrenia. Today, there is no drug approved to treat negative symptoms of schizophrenia.
It is, for a few decades now, been one of the most significant unmet needs of these patients. The negative symptoms, by the way, are the more social withdrawal aspects of the disease as opposed to the psychosis represented by hallucinations and delusions primarily. We also have a phase II program in major depressive disorder. As many of you are probably aware, several of the existing antipsychotics are approved to also treat depression. In fact, the word antipsychotic is a little bit of a misnomer. These drugs are also approved to treat agitation in schizophrenia patients and many of them are approved to treat major depressive disorder, some of them bipolar depression as well. One of the challenges in using these drugs, these traditional antipsychotics in major depressive disorder, is you get the whole host of side effects that I described earlier.
That results in physicians being a little bit tentative in how hard they push the dose of those drugs. We think with our very favorable tolerability profile and unique pharmacology, we have an opportunity to perhaps benefit those patients in a very different way. Spend just a couple of minutes now on Alzheimer's disease psychosis. I mentioned that we have positive results from our phase II study that we reported in the fourth quarter. We will be advancing into phase III later this year. There are 5.4 million Alzheimer's disease patients in the U.S., approximately half of them are diagnosed. Alzheimer's disease psychosis afflicts about 25%-50% of diagnosed patients. Should pause here for just a moment and note that the reason it's such a wide range is because we have to rely on literature surveys in this arena.
We had to do that in Parkinson's disease psychosis as well, because in neither of these disorders is there a diagnostic code for Parkinson's disease psychosis or in this case, for Alzheimer's disease psychosis. We will ultimately do, it's very substantial and tedious work to try to get a better fix on that. As we progress through clinical development, we'll ultimately do that in Alzheimer's disease psychosis in the way that we did in Parkinson's disease psychosis. It's safe to say it's a very substantial unmet medical need. It's a significantly larger population than what we're pursuing currently in Parkinson's disease psychosis. There's no drug approved by the FDA for AD psychosis, and I mentioned the side effects that these other drugs carry.
Just one other very significant point to make as it relates to Alzheimer's disease psychosis, and you'll hear in a second, it also relates to Alzheimer's disease agitation. That is, in a similar way to Parkinson's disease psychosis, where traditional antipsychotics have the potential for worsening the motor symptoms, in this case, it's been well established that traditional antipsychotics are associated with worsening of cognitive function in Alzheimer's patients. Again, a similar situation where when these patients develop psychosis and you use traditional antipsychotics, they have the consequence of worsening the cognitive symptoms. It's not insignificant, by the way. It's equivalent to about one year of disease progression. I mentioned our -019 results. This was a phase II double-blind placebo-controlled study in 181 patients with AD psychosis. On the primary endpoint, we established statistically significant reduction in psychosis on the NPI nursing home psychosis scale at six weeks.
Pimavanserin improved the psychosis score by 3.76 points. That was from a 9.52-point baseline versus a 1.94-point improvement for placebo. Pimavanserin did not impair cognition as measured by the MMSE score over 12 weeks of treatment. Let me repeat that. We did not impair cognition. The traditional antipsychotics well established that they do, but we did not. That's a very significant potential benefit that we have. Of course, we'll be following up on that in our phase III development, but a very significant finding in this study. Of course, as we observed with Parkinson's disease psychosis, pimavanserin was very well-tolerated. Safety profile was consistent with what had been observed in previous studies. Most common adverse events were falls, UTI, and agitation. Importantly, there was no difference in mortality between pimavanserin and placebo groups.
I should note that that was despite the fact that the average age of patients in the Alzheimer's disease study was 13 years older than in our Parkinson's disease study. It was a very elderly, very frail population. We're very pleased to see such a favorable safety and tolerability profile. As I mentioned earlier, we're now advancing the program into phase III. We'll do that by the end of the year. Alzheimer's disease agitation. Many of the things I've said about Alzheimer's disease psychosis also apply to Alzheimer's disease agitation. Same epidemiology, 5.4 million patients, approximately half diagnosed. In the case of agitation, again, relying on data in the literature, it appears that about 40%-50% of diagnosed patients with Alzheimer's suffer from Alzheimer's agitation.
I should also note that the type of agitation we're talking about here is not the type of agitation that we might experience if we try to take the subway at 5:30 P.M. this afternoon. It's a very pervasive, life-altering type of agitation. Here too, there's no drug currently approved by the FDA for AD agitation. It is a chronic condition that leads to a very diminished quality of life, and it is frequently a precursor to nursing home placement. I mentioned schizophrenia, inadequate response. Schizophrenia afflicts about 1% of the U.S. adult population. Actually, that's true globally as well. About 30% of patients with schizophrenia have an inadequate response to antipsychotics. About a third of them don't respond at all. About a third, more or less, achieve an adequate response. About a third or 30% of them have a response, but they still have significant symptoms.
We think there's an opportunity to administer pimavanserin on top of these other therapies and get a better result. What's done today is many times, patients receive multiple versions of the existing drugs. Whether you get additional efficacy or not by administering very similar drugs on top of each other, you definitely get additional side effects. Same things I've said on inadequate symptoms hold true on negative symptoms in terms of the epidemiology. Here, it's about 40%-50% of patients suffer from prominent negative symptoms. Here too, this is an adjunct therapy approach where we believe by going on top of the existing antipsychotics, we may be able to boost the signal on negative symptoms in order to achieve a better result. Existing antipsychotics show an improvement on negative symptoms, but it's not significant enough to warrant approval by the FDA.
Our hope and what we'll be exploring in this study is our ability to boost that signal in a way that would achieve approval for that indication. I've already talked a little bit about major depressive disorder and the challenge with existing therapies. I'll just quickly note that MDD afflicts approximately 16 million adults in the U.S. It's a sadly very significant portion of the population, and we believe with our unique SSIA profile, that they have the ability to significantly help these patients. We are headquartered in San Diego. We have 420 employees. Cash position at the end of the second quarter this year was $417 million.
Our key priorities for the year, I've spoken to most of these already, but just for the sake of completeness, are to advance, continue building momentum in the commercialization of NUPLAZID, to advance our Alzheimer's disease psychosis program into phase III, and to continue advancing the enrollment in these other indications. With that, I'll stop my prepared remarks and turn it back over to Chris.
Thanks, Steve. A very nice presentation. Definitely appreciate your attendance today. Maybe I'll start off with one and then open it up for questions on the floor. If not, I'll come back with additional questions. But just given the recent increase in the sales force, particularly in the long-term care setting with pimavanserin, what can you tell us about the success and the penetration in this group? And if it's too early, when do you expect to see a significant uptick in this segment?
When we launched, I mentioned there's no diagnostic code, so it's a little bit challenging to get a good feel for just who's a PDP prescriber and how much do they prescribe. But we did a lot of work to look at the intersection of physicians that write drugs to treat Parkinson's and write antipsychotics. That gave us pretty good clarity with neurologists in terms of who's writing what. With psychiatrists, much less so because they don't write Parkinson's meds, obviously, so it's more challenging. And in the long-term care setting, also a little bit more opaque in terms of where to go. When we launched the drug, we felt like the long-term care setting would represent about 20% of the business.
I think about six months in, we developed the view that whether it's going to be substantially more than that or not, we'd have a difficult time just keeping up in long-term care with the force that we have. We expanded the field force in April of this year. What I can tell you now is that it's about 30% of the business today. It has grown more substantially than we would have projected when we launched the drug. I feel like we're getting really good traction there. What I wouldn't want to set the expectation that what you should expect to see is a sudden kick in the revenue curve. We're continuing to grow on all sectors and continuing to get really good traction. My point is we're already in long-term care.
We expanded it because we didn't want to get behind, we are seeing it actually grow to be a bigger proportion of our business than we originally imagined.
Great. Thanks, Steve.
One of the compelling arguments was that it keeps delaying the time till institutionalization of patients. Are you in any way in the post-approval process able to track where your patients are coming in that are not long-term care and other things, plus what they become over time?
Yeah, it's a great question. There are many things that you typically would want to do and that we are doing when you get to post-approval types of studies. I don't want to comment specifically on that. What I will say is that's a very long-term assessment, and there are many things that we're looking at to try to just better understand disease progression, the impact of intervening earlier versus later, et cetera. Whether we ultimately establish that kind of a benefit that is delayed institutionalization or not is something that's under consideration. I can't speak specifically to that at this juncture.
With the four phase II studies that you have, what's your expected time to enrollment?
Can you repeat the question?
Yeah, I'm sorry. Could you repeat the question?
With the four phase II studies you have, what's your expected time to enrollment?
Yeah. In those four studies, they all began very close in time in the fourth quarter of last year. It's a little bit too early in the enrollment of those trials to be able to predict exactly when we'll finish enrollment. But what we said at the time and remains true today is these kinds of studies in CNS and these sizes of studies typically take two to two and a half years to run. That's probably the best kind of zip code guidance we can give at this point in time.
Obviously phase II ADP trial, agency appearance was probably not what you predicted. I know that's probably two to four years. What learnings have you taken in terms of the design for your phase III trial?
Yeah, it's a great question. I'll try to make this quick because I know we have limited time. I'll just say with any phase II study, your objective is to try to learn as much as you can to inform what to do next. Should I stop? Should I go? Et cetera. We came out of that study. What you don't always get is a really clear roadmap for what you would do in the next study or in phase III development. We got that in this study, and as I mentioned earlier, we've now had an end-of-phase II meeting with FDA. We went in with a plan. We came out of that meeting with exactly the plan we went in with, and I think that just speaks to the clarity that we have in terms of how we proceed into phase III.
We'll see that sometime before the end of the year.
You will see it before the end of the year. You will. Yeah. Correct.
Okay.
Great.
Thanks, Steve. Thanks, Kyle.
Thanks, Chris.