All right. Good afternoon, everyone. My name is Corey Kasimov, Senior Biotech Analyst here at JPMorgan. And it's my pleasure to introduce our next company, Acadia Pharmaceuticals and CEO, Steve Davis. Please note that following Steve's presentation, there will be a breakout just down the hall in the Sussex Room.
So with
that, turn it over to Steve. Great. Thanks much, Corey. And thanks to each of you for being here today to learn a little bit more about Acadia and NUPLAZID. I think everyone in the room has probably recognizes that there are certain risks and uncertainties inherent in the pharmaceutical business.
Please see our most recent SEC filings for a description of these risks as they relate to our business. At Acadia, we are building a leading CNS company. We laid the foundation for this in 2016. On April twenty nine of last year, we received FDA approval for NUPLAZID as the first and only drug approved for Parkinson's disease psychosis. A month later, on May 31, we launched NUPLAZID with our independent national sales force.
In the fourth quarter of twenty sixteen, we launched four major CNS studies to potentially expand the label for NUPLAZID. Also at the tail end of the fourth quarter of last year, we reported out positive top line results from a study that had started a couple of years ago. This is a Phase II study of pimavanserin in Alzheimer's disease psychosis. The centerpiece for pimavanserin and for ACADIA is the selective serotonin inverse agonist mechanism or the 5HT2A blocker, blocking mechanism of pimavanserin or NUPLAZID. It's known by its brand name.
Of course, the first application of this very unique new class of drug is in Parkinson's disease psychosis where we are now approved and launched and the drug is administered as monotherapy. In addition, as I just noted, we have positive Phase II results in Alzheimer's disease psychosis. And just to pause for a second, there's a commonality between Parkinson's disease and Alzheimer's disease psychosis I'd just like to touch on. In Parkinson's disease psychosis, Parkinson's patients, of course, suffer from a lack of dopamine and therefore take dopamine replacement therapy or dopamine agonist to supplement the deficiency they have on dopamine. All other antipsychotics that work through other mechanisms, not SSIA, block dopamine and therefore have the potential to interfere with the dopaminergic therapy.
So you have a situation where until NUPLAZID was introduced, doctors treating Parkinson's patients had to choose between or compromise between aggressively treating the motor symptoms or aggressively treating the psychosis. And available options used off label had the potential to interfere with the primary symptom of the disorder that is the motor symptoms. It's not an altogether different situation in Alzheimer's disease psychosis. Those patients are not taking therapy, but it's been demonstrated that the off label use of antipsychotics today interfere with the primary symptom of that disease as well. They make cognition they impair cognition.
It's not insignificant. It's equivalent to about one year of disease progression. So a similar situation where in both diseases, the existing class of antipsychotics working through more traditional mechanisms have potential to exacerbate the primary symptoms of those diseases. We also initiated last year a study in Alzheimer's disease agitation. This is also a monotherapy approach.
And in the fourth quarter, we initiated a study in schizophrenia inadequate responders. This is schizophrenia patients who don't adequately respond to a single antipsychotic. We have a situation today where schizophrenia patients frequently don't adequately respond to one antipsychotic. All of the antipsychotics on the market that are approved for schizophrenia are brothers, sisters and cousins of each other. So we have a situation where physicians frequently, when patients don't adequately respond to one, they add on a second and sometimes a third.
So whether you're getting added efficacy or not is probably debatable. You're definitely getting additive side effects with that kind of an approach. So we need better options to treat these schizophrenia patients. Schizophrenia negative symptoms has long been perceived as the most significant unmet need in schizophrenia patients. This is the lack of socialization, the flat affect that these patients suffer from, etcetera.
And there's no drug approved today to treat the negative symptoms of schizophrenia. I'll go into a little bit more detail in a moment about our approach and how we think that we could change that paradigm. And then the last indication that we've now entered into later stage development is in major depressive disorder where we think pimavanserin with its very unique mechanism of action has the potential to be an important adjunctive therapy for patients taking SSRIs or SNRIs. So in total, or in sum, we're pursuing six different disease states, six different indications. In three of these, we have demonstrated an antipsychotic effect.
We've done that in Parkinson's disease psychosis, of course, were approved. Earlier in development, we did that in schizophrenia, showed a statistically significant improvement in psychosis by adding pimavanserin to an existing antipsychotic. And most recently, we've now demonstrated that antipsychotic effect in Alzheimer's patients as well. I'm going to drill down a little bit more on PDP and the opportunity there. As I mentioned, NUPLAZID is the first and only FDA approved therapy proven to reduce the symptoms of hallucinations and delusions.
And we do that without impacting motor function. As I mentioned, NUPLAZID represents a paradigm shift. Not only is it first drug approved in the indication, new class of drug, it also has a very favorable tolerability profile in this frail and elderly population. Parkinson's disease psychosis is a serious and debilitating condition. It's represented primarily, the hallmark of this disorder is primarily hallucinations and delusions.
So of course hallucinations are seeing something that's not there or perceiving a real object as something else, something that it's not. Delusions are firmly held false beliefs, examples of this. These are both two examples that happen very frequently with Parkinson's patients for reasons we don't fully understand, but spousal infidelity or theft by a caregiver. As you can imagine, if you've got Parkinson's patients, limited mobility, frequently the caregiver is a spouse, these kinds of delusions can be very, very disruptive, not only for the patient but their families. Parkinson's is a progressive disease.
Parkinson's disease psychosis tends to worsen over time as well. And it, of course, as I was describing, can severely impact the quality of life and daily living of these patients. It is a leading cause of nursing home placement for Parkinson's patients. Just going to touch briefly on the clinical data from the single pivotal study that served as the basis of approval for NUPLAZID. NUPLAZID was designated as a breakthrough therapy by the FDA and as I mentioned, was approved on the basis of the single pivotal study 20.
There we demonstrated that a thirty four milligram dose of NUPLAZID showed a thirty seven percent improvement on the SAPS PD scale, the primary endpoint in the study, versus about a fourteen percent improvement for placebo at week six. When we crosscut that, look at it a little bit more granularly and say, okay, but some patients benefit more than others, how does NUPLAZID stack up at various breakpoints? And we look at those patients that improved by one point, by two points, three, five, seven, ten, and those patients that have what we call a complete response, a complete remission of all psychotic symptoms. What we see is a meaningful improvement of NUPLAZID over placebo at each of these breakpoints. And I note two things here.
One is when we look at a complete response, see that about fourteen percent of the NUPLAZID patients achieved a complete response versus one percent on placebo. The other thing I might note is that the opposite end of that scale, those patients that improve by only one point, you just recognize that can be a very meaningful change. Just a one point improvement can represent the difference between a patient having hallucinations daily versus weekly. So just reducing the frequency or the severity or the frequency and severity of hallucinations can be very meaningful in terms of the care of these patients as well. Commercial focus for 2017 is to establish NUPLAZID as the first choice, best choice for Parkinson's disease psychosis.
We are targeting about twelve thousand neurologists and psychiatrists, noting today that we are expanding our sales force from 133 to approximately 155 reps. This is primarily to increase penetration to long term care. We knew when we launched NUPLAZID seven months ago that we had better line of sight on some physician groups versus others. We knew long term care is a more complex sale, involves many more constituents. And we recognize that we need to get some experience in the field before determining whether we needed to adjust there.
We determine we've got a compelling need to add additional reps there. So that's what we're doing. On the payer front, I'm often asked, so how does is the launch going or how does the launch compare relative to what we expected? And always say, up to this point in time, the thing I think is most remarkable about the launch is how closely it's gone to our plans. And I think the payer front is one really good example of that.
We did exhaustive payer research, felt like we knew exactly what would be the most fair and best price for the drug. And the payer reaction has been almost exactly what we expected. It might even be a hair better. So I think we're very pleased that we're now on all Medicare Part D formularies. Antipsychotics are in a protected class.
So we needed they needed to make these formulation decisions within ninety days. They've done that. And we also knew at the time we launched that commercial plans take longer. They take another six or nine months. And so we're on about 35% of the commercial plans that we expect to be on there.
Same thing holds true that I said about payers as it relates to physician feedback, both when we look at anecdotes we receive through our field force as well as the market surveys that we're pulsing the market with from time to time. We see a very strong opinion of NUPLAZID and NUPLAZID Connect. And physicians are very, very pleased with the drug. We see a of course, they're not out administering scales like you do in a clinical study, but the reaction we have is very strong, very supportive and we're very thrilled with the response so far. Focus right now is increasing awareness through our KOL speaker programs.
We have a lot of peer to peer activities going on, not only with KOLs but also through our speakers bureau. We have a very strong presence at medical meetings. We have multimedia campaigns. We're progressively rolling out more and more of those. We've recently started direct to patient programs.
Just another quick snapshot of the pipeline. Of course, we start with PDP, where NUPLAZID is approved. We'll go through each of these in detail. But I just wanted to note that in addition to approval in PDP, have five other indications that are now in late stage development. Also, I'd just like to note one footnote at the bottom, just recognizing that at least as of today, we're only approved in The U.
S. We've made a recent determination to defer the filing of an MAA for European approval. That we've made that primarily on the basis of positive results we have in the ADP or the Alzheimer's disease psychosis study. And quite simply, once we have approval in Europe, assuming that we are approved in Europe, we'll have a ten year period of data exclusivity. That clock starts with the first approval.
So of course, if we start earlier with PDP, then we'll have less time to capitalize on other indications during that ten year period. So we've made a determination we're going to hold off on the MAA filing for now. We'll reevaluate that next year when we have additional data on other indications. But on the basis of the positive results we have in ADP, it's moved the needle in favor of deferring for now. Alzheimer's disease psychosis, I'll go I'll click kind of quickly through each of these indications.
There are just a few things that I think are important to note. Alzheimer's disease psychosis Alzheimer's disease afflicts about five point four million patients in The United States. Approximately half of them are diagnosed. ADP or AD psychosis afflicts twenty five percent to fifty percent of these diagnosed patients. I should mention the reason we have a range is there's no diagnostic code for these patients.
It's also not for PDP, but the literature suggests about a quarter to a half of AD patients have ADP. There's currently no drug approved by the FDA for AD psychosis. And I've mentioned the fact that current antipsychotics not only carry significant side effects in terms of sedation and other liabilities, but are associated with a worsening of cognitive function. The Phase II results that we announced in December were from our Phase II exploratory double blind placebo controlled study in about one hundred and eighty one in one hundred and eighty one patients, evaluating thirty four milligrams of pimavanserin versus placebo. We had a statistically significant result on the primary endpoint.
We improved on that primary endpoint, the NPI nursing home scale. We improved by a score of 3.76 points off of a baseline of 9.52 relative to placebo improvement of 1.94 points off of a baseline of 10. So I just should note that those movements in drug and placebo group are very similar to what we saw in the '20 study that served as the basis for approval in PDP. Importantly, pimavanserin did not impair cognition as measured by the MMSE score over twelve weeks of treatment. The drugs were very well tolerated.
In fact, I would say now we've just added significantly to our safety database from what we had in PDP. And very pleased to see that despite the fact that the average age of the patients in the ADP study was about ten years older than in the PDP study, Drug was very well tolerated. So just to sum up on ADP or AD psychosis, our SSI mechanism of action, we believe, provides an attractive clinical profile in these patients where we've demonstrated antipsychotic efficacy without impairing cognition. And as I noted, a very favorable safety profile. So the next step is we'll be entering into Phase III registration program or initiating a Phase III study later this year.
Alzheimer's disease agitation. We initiated a study in the fourth quarter. Again, same demographics, five point four million patients, approximately half are diagnosed. In this case, it's estimated forty percent to fifty percent of those diagnosed with Alzheimer's disease suffer from AD agitation. I know many of you have heard me say this before.
I should just footnote that the kind of agitation we're talking about here is not the kind that we might experience if we're grabbing a cab in the rain. But it's a very pervasive life altering type of agitation. Today, there's no drug approved by the FDA for AD agitation. And same thing holds true here. Atypical antipsychotics are used off label some for agitation as well.
You have the same cognitive impairing liabilities for these patients as well. The Phase II Serene study that we're doing in ADA is a twelve week study. It's a randomized, double blind, placebo controlled, multicenter outpatient study. We're in about four thirty Alzheimer's patients with agitation. We'll be looking at two doses of pimavanserin, thirty four milligrams and twenty milligrams versus placebo.
Primary endpoint of the study is at twelve weeks on the Cohen Mansfield Agitation Inventory Scale. Schizophrenia. I noted before that schizophrenia patients frequently don't respond adequately to a single antipsychotic. Just to give a little bit more granularity around that, about a third of schizophrenia patients don't respond to antipsychotics. About thirty percent or almost another third have a response but it's an inadequate response.
And then about a third of them adequately respond to a single antipsychotic. I should have noted that schizophrenia affects approximately one percent of The U. S. Adult population. It's actually the same across the world.
Current therapies are very significant. I think everyone is probably familiar with the very significant side effect burden of these drugs in terms of metabolic issues, sedation, flattening of affect, etcetera. We believe our SSI mechanism and safety profile has the potential to be a very important addition as adjunct therapy. So just to be clear, this is an area where we're looking at adjunct therapy. The objective would not be to try to displace the many generic drugs that are used to treat schizophrenia, but instead for those patients that don't adequately respond to add on to existing therapy in order to boost the signal, do so with a very unique mechanism so that we're not just doing more of the same and with a mechanism that's demonstrated a very favorable safety profile.
Study here is a Phase III study with three eighty patients that demonstrated an inadequate response to current antipsychotic treatment. Here we have a flexible dosing regimen that we've employed. The patients will start at twenty milligrams of pimavanserin and can be adjusted either up to thirty four or down to ten. Patients will be evaluated over a six week period on the PANSS scale or the positive and negative syndrome scale. I noted earlier that negative symptoms has been a very significant unmet medical need in schizophrenia.
Same demographics here. It's one percent of the population. It's believed that forty percent to fifty percent of patients suffer from prominent negative symptoms. Again, this is the social withdrawal aspects of the disease. So this is one difference between schizophrenia inadequate responders and schizophrenia negative symptoms.
Today there is no drug approved to treat negative symptoms of schizophrenia. Many of the antipsychotics move the needle. They don't move it enough. So none of them have been approved for negative symptoms. So what we'll be exploring in the clinic is can we boost that signal by layering pimavanserin on top of existing antipsychotics.
Can we boost the signal sufficiently to get that approval? This study is a study for twenty six weeks. Patients will start again, flexible dosing regimen. They'll start on twenty milligrams of pimavanserin and can be adjusted during the first eight weeks either up to thirty four or down to ten milligrams. The study will involve three eighty patients and the primary endpoint will be measurement of the negative symptom assessment 16.
Major depressive disorder is the final indication that we've initiated studies in. MDD afflicts approximately sixteen million adults in The U. S. It's characterized by depressed mood, loss of interest, pleasure in daily activities, etcetera. The majority of patients do not respond to initial antidepressant therapy.
So I think as most of you are familiar with atypical antipsychotics are approved for and used as adjunct therapy to treat these patients. When we talk to the medical community, what we frequently hear is while those drugs boost the signal, still get even at the lower doses used for as adjunct therapy and depression, you still get a lot of the side effect vagus. You get a lot of akathisia or this feeling that you have bugs under your skin. You get it's not common, but you can get tardive dyskinesia that can be permanent. And so it weighs heavily on physicians' minds.
Of course, the last thing they would want to do is take their difficult to treat depressed patient and give them a permanent motor disorder. So we think the mechanism of action pimavanserin, which does not contain any dopamine, dopaminergic activity, could be an ideal therapy that could have a much cleaner safety profile than we see with existing antipsychotics and could possibly enable, through its unique mechanism, the ability to dose higher. So this study is our Phase II CLARITY study. It's a ten week randomized placebo controlled study involving one hundred and eighty eight patients. And here, we'll be looking at a thirty four milligram dose of pimavanserin on top of background antidepressant therapy versus placebo on top of background antidepressant therapy.
The primary endpoint here is the HAMD or the Hamilton Depression Scale. Just real quickly, we're headquartered in San Diego. We have three seventy employees. Cash position at September at the end of the third quarter was $589,000,000 Key priorities for us at this moment in time are: number one, by a wide margin is to continue the successful execution of the new PLANZID launch Second is to advance Alzheimer's disease psychosis into a Phase III study on the basis of the positive results we received in our Phase II ADP study and then to advance these other indications this year. The work that we do this year will be very important in terms of getting to the finish line for these studies in the future.
So with that, I'll wrap things up, and I think we'll have Q and A in the breakout room. Okay. Thank you. Well, thanks, everyone, for coming out. I know we're getting started a couple of minutes late, so why don't we just jump right in, and we'll take questions from Sorry?
Yeah.
Yeah. Well, got a got a lot more to talk about now. It's kinda hard to jam it in, to be honest with you. So, Lisa, you'll just let us know when
we're ready.
No worries. Okay.
Yeah. Good? Okay, great. Well, thanks very much everyone for coming out.
As I mentioned in the presentation, 2016 was a foundation laying year for us. This is a really, really important year. We'll really define the value of the company for the next decade and beyond in 2017. So I'll pause there and just ask who has the first question.
Can you talk a little bit more about the decision to upsize the sales force? Maybe what was different about the long term care centers than maybe you thought previously, or where you see added opportunity there?
I'll start. Terry, feel free to jump in if you like. I think the starting point is, first of all, me just preface by saying, we knew when we launched that that's where we had a little bit less visibility. It's been clear that we need a bigger force to cover the business. There's more business there than we're able to cover currently.
It's a pretty rare thing when you've got reps saying, I can't cover this. Reduce the size of my territory. It's usually just the opposite. That's not the reason we're doing it, just as a further indicator, we clearly need more bandwidth in order to cover the work there. Long term care is just more complex.
You've got a lot more people involved in doing it. It's a little bit less line of sight for any company that launches into long term care.
One of the other new disclosures, the decision to defer the MAA in Europe. Previously you were waiting on the resolution of a pediatric thing. What's happened there? And did that have any bearing on this decision? Was it strictly
Yeah. It actually had nothing to do with it. Actually Yeah, I'm sorry. Yeah, thanks. Okay.
The question is, I announced in the presentation that we're deferring on the MAA filing for approval in Europe. Corey's question was correctly noting that we'd previously deferred in order to get alignment or agreement on a PIP, or Pediatric Investigation Plan, with European authorities, which is a prerequisite to filing for approval. We actually have that now. We did agree on a PIP. That also came late in the year.
Very quickly after that, we got positive results from the ADP study. The decision to push back has nothing to do with the PIP, because that's actually behind us now. Literally, we were ready to push the button on the MAA filing. We got the results in ADP and just determined We knew all along, these things, as they often are, was a multifaceted consideration in terms of what would be the best strategy for us. We got the ADP results and that moved the needle in favor of waiting.
Quite simply, it's a trade off between potentially launching sooner and just PDP, but having less time for other indications versus frame shifting and having more time for potentially other indications. We'll reassess again next year when we start getting some clinical data back on these other studies.
In terms of ADP, obviously, you stated your intention to move into phase three registrational study. What what are your thoughts right now in terms of what that study might look like? The exploratory phase two was just that you've had some issues that you talked about in the past and how you might have done things differently. So now it's starting to scratch the phase three. What are your early thoughts on what the design might be like?
Yeah. So I'll take it at a high level, and Serge may wanna may wanna contribute as well. Yeah, sorry. I'll try to not make you remind me every time. Sorry about that.
The question is on the ADP study, just kind of rationale behind the decision to move forward into Phase III. Just as a reminder, the 19 study that we reported out is an exploratory phase two study. The objective with those kinds of studies is to get information to tell you two things. One, should I go forward? Two, if I'm going to go forward, what should I do differently or the same?
On both of those fronts, we overachieved the objective, I think. We've got a very good signal of efficacy. Equally importantly, and it does not always happen in any therapeutic area, particularly in CNS, where you have more subjective endpoints, but we've got a very clear vision for how to go forward. We will report additional details on that later in the year, probably at a medical meeting or in a publication. Think as all of you know, there is some competition in the area and we want to make sure that we maximize the benefit of the very rich database that we have for our own account, we'll let other companies go do their own studies and learn what we've learned in this.
For now, focus is to take those learnings, apply them to the next study, As I mentioned, our anticipation is we do have a Phase II meeting we plan to have with FDA, so subject to timing around that, our intention is to start Phase III in the second half of this year.
Do you have any commentary on the design?
The question is, any commentary around the design of the study? The short answer is, because we don't want to enable other people who might be enrolling studies in this space too, we're really not going to have a lot that we can say about it. A lot of that will become more obvious when we start the study and the study design is described on clintrials.gov, etc. But between now and then, so the sequence most likely will be starting the next study either shortly before or shortly after that, some kind of publication. Again, that's always subject to third parties and something not totally within our control.
Through the combination of what will get published on contrails.gov and publication, I think it will be really clear the path that we're taking.
I would just add that the study is really a treasure trove of learning for us, both from the perspective of how to do the Alzheimer's disease and Crohn's disease trial as well as how to enhance the signal of pimavanserin efficacy. And we actually have a fairly good idea as to what would we want to do in a phase three trial and what we'll be proposing to FDA. Obviously, we're still looking at the data to a great detail. But the value of this trial is not only in the fact that as Steve said, we have evidence of efficacy, but it's also a clear path for us out in the registration trial.
Recognizing that you just reported top line, you haven't presented detailed results yet. It's only gonna be brief. Do you have early KOL feedback on the results?
We will be discussing the we will discuss some of the results with the principal investigator on the study, and we'll be discussing further and then
Yeah. So we we actually are doing some additional dosing in some of the studies that we're doing. I'll let Serge speak to that.
Right. In our agitation, Alzheimer's agitation trial, we are evaluating two doses, twenty mg and thirty four mg. In our schizophrenia trial, both trials are flexible dosing between twenty ten and thirty mill thirty four milligrams. So we are essentially exploring other doses in these trials. In the depression trial as well as in Alzheimer's Alzheimer's psychosis trial, we're pretty much settled with those.
Particularly encouraging for us in the Alzheimer's psychosis study was in this very elderly population, 86 years average age, we actually saw tolerability, safety profile that is even slightly better than what we saw in Parkinson's disease. So it's very encouraging for us from that perspective in terms of doses seem to be well tolerated and safe, and
we we saw efficacy. There any particular reason why the tolerability and Alzheimer's agitation can be different than
The question was, is there any reason to think that tolerability would be different in the ADA study versus ADP, given that we're the ADA study, we're exploring both thirty four and twenty mg?
I'm not aware of any specific reason why would that be the case. When we were thinking about the agitation, Alzheimer agitation trial, we knew much less about the potential dose, and we wanted to explore a range of doses rather than just go with a single dose.
Are you willing to comment yet on the potential timing of these various trials you have going on for top line areas with Serene, Enhance, Advance, and Clarity?
The question is can we comment on the timing of when we expect results from the studies that we started in the fourth quarter? Really simply, we're not yet. We need to get a little bit further into enrollment and then we'll have better clarity ourselves and we'll be in a position to talk about that. Having said that, these studies usually take two, two and a half years to run, so it gives you at least a zip code idea of when studies could read out.
I guess a related question that's also somewhat accrual dependent, is with all this clinical work going on, how should we be thinking about R and D trends for 'seventeen?
So Todd, you want take that? Sure.
The question is R and D trends for '17 given the enhanced trials. I think as we mentioned on our Q3 call, we were expecting R and D expense in Q4 to be up in the mid $30,000,000 range, which is a significant increase over the first half of the year as we continue to prepare for these four trials to begin. With that, we're obviously adding another trial and increasing enrollment in here in 'seventeen, and so we expect the R and D to continue to trend up in 'seventeen relative to Q4. But we did get most of Surge's organization built in the back half of twenty sixteen. Because that generally sums up where it's headed.
It's really quiet.
You're doing a great job.
No. I'm surprised you just We could do this for a couple hours. Around. Just as far as the the PDP launch, the ongoing launch, what what are the the most significant barriers at this point in time? I'm pretty simple as just blocking and tackling and doing what you're doing.
Or are there other impediments you kind of don't need to sort of work through to gain that additional credit?
Yes. So the question is, on the PDB launch at this point in time, are there significant impediments, or is this more just blocking and tackling that you need to work through? As I mentioned, the thing that's most remarkable to me is things have lined up very much as we expected them to based upon the best information That applies whether it's the payer reaction, physician reaction, etc. There are no
are
issues that are facing us. It's just we're executing on exactly what we thought. Now that could change tomorrow, but as of today, it's been very much in line with what we expected. I know you guys have heard me say this a lot, but this quarter's revenues are important, we care about them. That's not the most important thing.
We're not executing the launch in a way designed to maximize Q1 revenues in 2017. We're executing in a way designed to maximize revenues in 2018, 'nineteen, 'twenty, and beyond. From that perspective, I think we're laying a great foundation. It's a paradigm shift, and as we said long before we launched, paradigm shifts take time, but then they have the potential to build and and build, and that's what we're seeing.
Bit more resistant to try initially?
Broadly speaking, I would say the physician feedback has been very much in line with what we expected and what we knew about the drug from the clinical studies. That is to say, would be very, very positive. That's true whether we're gathering anecdotes through the field force, as I mentioned in my remarks, or the market research that we've done. With any drug launch, irrespective of therapeutic class, but specifically when you're dealing with chronic lifelong therapies, physicians tend to segment out into different groups. There will be some physicians that are early adopters and they're putting a patient, another patient, another, another, another on drug as fast as they can.
There are other physicians that will never write the drug, of course. There are other physicians that just don't write drugs for the first six months or the first year. We're seeing all of that, and I think we've got very good intelligence in terms of trying to identify what are the most appropriate pressure points for us to engage in, in order to educate physicians in the best way possible so that as many patients as possible can benefit from the drug. All of that's gone extraordinarily well.
When you see physicians trying the drug, is it they try just a couple of patients initially to see how those patients do? When they are trying a couple of patients, are they doing it at full doses? Do they experiment with the dosing themselves?
Two questions here. When we see patients experiment with the drug, are they doing just a patient or two? And are they giving the full dose or a partial dose? Let me take them one at a time. There's no doubt, and we knew this would be the case, as you launch the drug, it's a mix.
In terms of just where physicians are, it's always a mix, right? Some full adopters, early adopters, some that are more in trial mode, and some that are in wait and see mode. That mix will change as we progress through the launch. As of today, we've got all of those. We definitely have some physicians that have written once or written twice.
You'll have some physicians who say, I'm going run my own one person clinical study. I want to see the drug in just one patient, and I'll wait three months or six months to see another. You definitely have some of that. What we're seeing is every week we're adding physicians, we're adding patients, and we're seeing this very progressive build that we've described. In terms of dose, we mentioned before we launched the drug that of course the presentation is two seventeen mg tablets taken together for a total of thirty four mg once a day.
Because the presentation is two tablets, there's the potential, and we talked about this before we launched the drug, that some physicians will probably start patients on a single pill and then move them to two pills, and we are definitely seeing some of that. I can't quantify it today, because we don't always know what a physician says to a patient or scribbles on a notepad versus what the prescription says. Again, I would put that in the same category. We expected there would be some of that. Are seeing some of
You also talked about expectations prelaunch for things like gross to net and patient compliance. Those tracking in the long lines?
Gross to net, again tracking, I know it sounded like a broken record, but was tracking almost exactly to what we thought. Persistence and compliance is one of the most challenging and elusive metrics to get your hands around with any drug that is a lifelong therapy drug. I think everyone knows this, you pour patients in the top of the funnel and then lose patients along the way, and then you have a steady, installed base of patients. That process of building that out takes some time. Of course, part of our job, and the job of any pharmaceutical company, to try to Of course, there are some patients that are just not appropriate, the therapy is not appropriate for them, so those patients, that's fine if they're off therapy.
But to try to identify whether there's either a lag or a loss that's not appropriate, and then to address those. Course, that's not unique to us, that's just the part of any launch, so we'll continue doing that. A key component of that is persistence and compliance. We're just not far enough into the launch. To be honest with you, we really don't even
have a good view
of that ourselves. We're just not far enough into the launch.
I think you mentioned in your presentation something about patient outreach. Just wanted to
see if give us a little
more color. Is that through patient organizations? Is that direct to consumer?
I'll take a very high level, and then Terry will give a little bit more detail. Did say direct to patient, not direct to consumer. There may be a place in time where direct to consumer, either through print or television, etcetera, may be appropriate. But the direct to patient outreach that we're doing now was planned. We needed to establish a certain brand awareness in physicians' offices.
Now, as we're progressing further into the launch, we've now activated some pretty significant direct to patient activities. I'll let Terri
So as Steve mentioned, we've planned this all along and we felt that this is a good time to launch this where we're going directly to patients and caregivers through a multi pronged approach. So it might be
websites, it might
be local meetings, it may be speaker programs specifically for advocacy groups. We've got a number of things that are in motion right now intended to really help educate both the patient and the caregivers and help them connect the dots so that they can speak to their physician about what they're seeing at home.
Just a really small example of that. Many of you have probably been in a doctor's office where you've seen they have a video monitor that has information on it. Sometimes it has the weather, sometimes it has news highlights from seeing in, etcetera. There are times where you can buy access to those and have information about your drug or your disease, so that's another component of the direct to patient activities. Sure.
Serge, do want to answer Well,
look at the totality of the data and variety of sensitivity analysis to really confirm the results at week six. We look at also the variety of subsets of patients and subgroups of patients. And when we do that, we clearly see that the therapeutic effect that we see at six weeks is a real effect. And that really encourages us to think that what we saw at week six is antipsychotic effect of the drug and it's not a spurious study. So the totality of the data gives us much more confidence that we will be able to design the trial where we will not only enhance the
effect of the drug, but
we will also be able to demonstrate that effect in a period of time.
And by the way, I should also mention, what Serge described, what almost always happens when you go from the exploratory phase two to a registrational study. Week twelve? What
we saw in pimavanserin are that the improvement that was achieved at week six fairly more or less stays maintained between week six and week twelve. And as a matter of fact, there is a small nominal improvement at week twelve over week six. What was unexpected was that what we observed is that in the placebo arm, we saw a significant improvement between week six and week twelve the soda that came close to the same level of improvement at week twelve and we lost the separation there. And in general, in the placebo group, which was not unexpected, there is much more variability and lability of data than we see in the pimavanserin are, which is fairly stable. It's just getting progressively over the entire period of the study.
So that's another element that gives us a confidence that what we saw is not related to a loss of effect. Effect.
You shared some quantification on your number of sales reps. How about MSLs? Are they being affected?
Yeah, no, it's a great question. I'm glad you asked. Should have mentioned, in addition to the reps themselves, of course, we have a management structure that's also in the field, managing them in the way of a significant MSL group. It's a very important component of making sure that physicians have the information that they need as well.
One question I have on the clinical side. You've had the schizophrenia data for some time now. Why the decision just now to move into Phase three as opposed to some time early?
Yeah. So I I can only speak to what we've done since, you know, the current management team has been on board. We felt like this data was really intriguing. I think there was an earlier plan by the company to run a monotherapy maintenance study, I think as we reconstituted the management team, we just felt like, look, let's make sure that we've really looked at this from cradle to grave. Let's make sure we understand as much as we can about what the clinical profile is or could be, and what the commercial considerations would be.
That's led us to the studies that we're doing. I'll just reiterate, negative symptoms in schizophrenia, the highest unmet need. It's a very, very significant issue for these patients. We think it's a very good investment to make to determine whether our unique mechanism will boost the signal sufficiently to help those patients.