Uli Hacksell - Chief Executive Officer and Director
Thomas Aasen - Executive Vice President, Chief Financial Officer and Chief Business Officer
Boris Peaker - Oppenheimer
ACADIA Pharmaceuticals Inc. (ACAD) Oppenheimer 24th Annual Healthcare Conference December 10, 2013 8:35 AM ET
Boris Peaker - Oppenheimer
I'm going to start with our presentation. My name is Boris Peaker. I'm one of the biotech analyst here at Oppenheimer. And the first company to present today is going to be ACADIA Pharmaceuticals, and it's my pleasure to introduce Uli Hacksell.
Good morning and thank you for joining us at this early morning. Let me first say that I am going to make forward-looking statements today. And therefore, I encourage you to read the risk factors that we have submitted in our SEC documents.
ACADIA is a biopharmaceutical company that is focused on CNS diseases. We have multiple product candidates, which are addressing really quite interesting markets. Our pipeline is led by pimavanserin, which is a Phase III product focused on Parkinson's disease psychosis.
We have already generated very strong data on the molecule, a great efficacy data, great safety and tolerability data. And we are now working on completing the Phase III program for pimavanserin, and I'll inform you much more in detail about this. We think that pimavanserin and the other molecules have a significant commercial role to play in ACADIA's future.
Now, the pipeline itself is, as I said, led by pimavanserin, the Parkinson's disease psychosis program, but we have also a lot of other opportunities with pimavanserin. We have 20 ongoing Phase II study in Alzheimer's disease psychosis, which we think will open up an opportunity for that major unmet medical needs as well, and we have already conducted a large Phase II study in schizophrenia. So there are multiple opportunities with pimavanserin.
Behind pimavanserin we have two clinical programs, development programs, in collaboration with Allergan, one chronic pain program and one glaucoma program. These programs are conducted by Allergan and paid for by Allergan. We also have two earlier stage programs, an ER-beta program and Nurr1 program, which may represents very interesting future products for ACADIA.
But the interest is very much focused on pimavanserin of course. This is a new chemical entity, a selective non-dopaminergic serotonin antagonist or 5-HT2A inverse agonist. It's a molecule with great intellectual property that takes us into meet 2028 with exclusivity and that doesn't include other opportunities for increased exclusivity beyond 2028.
As I mentioned, we have generated strong Phase III data that provides efficacy of the molecule and we also have shown that the molecule is very safe, well-tolerated, and we have done that in patients with Parkinson's psychosis. There is nothing approved for this indication. And we think that because of the major unmet medical need in Parkinson's psychosis, we have a molecule that really will make a difference for these patients.
The FDA seems to agree with us, because they provided us the opportunity to file our NDA based on one pivotal study, something which is quite unique when it comes from the psychiatry division of the FDA. We also see great expansion opportunities of pimavanserin beyond Parkinson's psychosis, and these include other problems that patients have when they start certain neurological diseases.
A lot of these patients, in addition to their basic neurological disease also had problems with psychosis. That is particularly true for Alzheimer patients, Parkinson patients, Lewy body dementia patients, et cetera.
Currently, these patients are treated with antipsychotic drugs off-label, despite the fact that these drugs have a black box warning for use in elderly demented patients with psychosis. And the reason for that black box warning is that the increase in mortality of the patients. They also increase some morbidity and they worsen the dementia that many of these patients suffer from.
So clearly the use of antipsychotics in this patient group is not good at all. And that's why we think that pimavanserin may represent completely different type of drug for these patients, which will be effective and well-tolerated.
We also see the other opportunity with pimavanserin in the psychiatrics space. We have already demonstrated that when we combine pimavanserin with a low dose of an antipsychotic agent in the treatment of schizophrenia, you can get a very interesting profile with high efficacy and with a much improved safety and tolerability profile as compared to a high-dose antipsychotic therapy. So lots of opportunities with pimavanserin.
But what we are focusing on now is Parkinson's psychosis, this is a condition which is quite common, it affects about 40% of patients with Parkinson's disease. And as we see the number of Parkinson's patients increasing over time with the growing population of elderly people. We will also see more and more people that suffer from Parkinson's psychosis.
And as I indicated earlier on, this is a very severe indication. It's in fact the major reason that Parkinson's patients have to go to a nursing home. The condition conceives of hallucinations and delusions, frequently related to a sexual component as well. So the patient may frequently accuse the spouse, so it's normally the caregiver of infidelity, which of course has a lot stress in their relationship. And eventually, both the patient and the caregiver cannot get along. And that's why the patient have to go to a nursing home.
And as soon as the patient comes to the nursing home, the life expectancy is halved and the quality of life is of course significantly decreased. And there is no FDA approved drug for Parkinson psychosis. So what neurologist do when the symptoms of the Parkinson's psychosis become untolerable is, that they give antipsychotic drug off-label, despite the fact that they have a number of problems with that therapy.
I already mentioned the black box warning for use of these agents in elderly patients with dementia and psychosis. And they also have the potential to worsen the motor symptoms of Parkinson's disease. The reason for that is that all the antipsychotic drugs of today lock the dopamine receptors. And the dopamine receptors are the targets for the Parkinson's therapy, dealing with the motor symptoms of the disease.
So all medications that they are normally given to a Parkinson's patients, L-dopa, dopamine agonists, MAO inhibitors, et cetera, are really there to increase the tone, the signaling of the dopamine receptors. So if you box those receptors, you are counteracting the motor therapy and patients may therefore get intolerable motor side effects. Pimavanserin does not at all interact with the primary receptors, as you can see on this slide. It only blocks the 5-HT2A receptor, and therefore it's well-tolerated by the patients, even in high dose.
Pivotal Phase III study that we conducted, it is called the -020 Study by the way, we demonstrated that pimavanserin really has an ideal profile for use in Parkinson's disease psychosis patients. We showed highly significant efficacy, as measured by different endpoints and as assessed by different assessors. We also saw a nice motoric tolerability as we have demonstrated over and over again. We don't affect motor symptoms at all with the drug and it's generally safe and well-tolerated.
We also saw another benefit of pimavanserin. These improvements of pimavanserin, improves the quality of sleep in the patients without being sedative. In fact, it does enhance the daytime wakefulness of the patient and we also saw a significant reduction in caregiver burden of pimavanserin, something which is of course very important for both patients and caregiver.
The study itself was conducted in North America, mainly in the U.S. We had two sites also in Canada. We had almost 200 patients in this study that has severe-to-moderate Parkinson psychosis. And we treated them for six weeks with pimavanserin, and those patients who completed the study could roll over into an open-label extension study.
The study was randomized one-to-one between 40 milligrams of pimavanserin and placebo, and the primary endpoint of antipsychotic activity as measured by a scale that is specific for Parkinson's disease psychosis, we called it the SAPS-PD scale, and we had achieved a motoric endpoint, the UPDRS to show that it did not negatively impact motoric function of the patients.
The study was initiated by a brief psychosocial therapy medium during two weeks, to ensure that we could take as much as possible of placebo response from the patients before they were randomized to placebo or pimavanserin. This initial running period consisted of enhanced interactions with site itself, and also teaching the patient and the caregiver to get along by focusing on the subject that was positive to both of them.
Now, the outcome of the study was stellar. The primary endpoint, the SAPS-PD improvement showed a highly significant separation from placebo at week six. We also saw a significant separation from placebo at week four, and the separation was clinically meaningful, exceeded three points on the SAPS-PD scale.
Importantly, not only the SAPS-PD measurement of psychosis improvement was significant. Also using other endpoints provided us with the same kind of significant improvement in psychosis as compared to placebo. The SAPS-PD scale was assessed by the way by centralized independent assessors. Highly educated psychologists, who interviewed patients and caregiver through a video linked and relapse time.
The CGI measurement of psychosis was in an independent way by the investigator, and as you can see the different rater and the different scale still provided the same kind of good outcome of the study. We also measured the motor control of the patients and we did not see any negative impact at all, of the drug on motor control. So we can really provide good and psychotic efficacy and maintain motor control with the drug, which is an ideal profile for treatment of these patients.
I mentioned some additional benefits of the drug in addition to the effect on psychosis. So we did measure sleep using a sleep scale for Parkinson patients in this study. And as you can see on the left-hand side, we had a significant improvement in the quality of nighttime sleep. This is a subjective measure that was provided by the patient themselves.
So the patients sleep better when they were on pimavanserin. And they had corresponding improvement in daytime wakefulness. So pimavanserin has this mild effect on how you sleep. So you sleep deeper when you take pimavanserin. It's not sedating. It doesn't help you to go to sleep. It just prevents you from waking up when you're sleeping at night.
And it does do, by helping you to spend more time in deep sleep and less time in superficial sleep and because of the lack of sedating effect of pimavanserin, you have the enhancement of day time wakefulness, which is important for Parkinson's patients, because they tend to suffer from excessive sleepiness during the day, just because they sleep so poorly. So we think this is an additional independent effect of psychosis, but a very beneficial additional effect.
I mentioned earlier on that we also saw a positive effect on caregiver burden. This is of course very, very important, because of the stressful relationship between caregiver and patients that really causes the patients to have to go to nursing homes. It was seen that caregiver burden is in fact reduced significantly when we give pimavanserin. And you can see also that the placebo drug had worsening of the caregiver burden over the six-week period.
So this is important, because it really shows the global effect on the patient, not only the psychosis, but everything is included here, because it all has an impact on how the caregiver proceeds, how difficult it is to deal with the patients. And this is something that we think that can provide a lead into health economical benefits of pimavanserin, which is of course very important, because it can also trigger a good pricing of the drug.
So in addition to having conducted this very successful Phase III study with pimavanserin, we have also through our open-label safety extension study obtained an enormous amount of Phase II data, which shows that pimavanserin's profile is completely different in this types of patients, and what you would expect to see with any one of the antipsychotic drugs that are marketed currently.
It's safe, well-tolerated and we have demonstrated that in many patients, in fact we had some patients on drug for over eight years. We have had more than 700 patient years of exposure. More than 200 patients have been on drug for more than one year. So we have a great safety database that throughout demonstrates a very attractive safety and tolerability profile of pimavanserin for these patients.
When we got this stellar data from the -020 Study, the pivotal Phase III study, we provided a very comprehensive briefing package to the FDA with all the efficacy data, all the safety data and all the other data that we have put together with pimavanserin. And we then surface a briefing package to the FDA, and asked them would you based on this package be willing to allow us to file on just one pivotal study.
And the FDA came back to us in writing, and verbally when we met with them face-to-face, a few days later and was very, very clear, this is in bold, you can read from the statement that we received from the FDA in writing, the -020 Study data, together with supportive data from the other clinical studies and other studies that we have conducted are sufficient to support NDA filing for PDP. So this was of course very exciting for us.
It may in fact we did not have to do an additional pivotal study, and actually can focus on the remaining aspects of the PDP package. But the CMC program quite have an indicating time limiting for us to come to the FDA, because we have not yet conducted the 12 month stability testing of regulatory batches.
So what remains for us to do is to complete the 12-month stability testing with pimavanserin, which was initiated in October this year. Until, also complete other supportive study, including the drug-drug interaction studies, which are required for drug of this type.
So the current target for NDA submission is near the end of 2014 for us, and again the time limiting aspect to stability testing, which we don't expect to provide any problems whatsoever, because we already know from the clinical batches, which is the same formulation as we use for the regulatory batches that we have over three years of stability. This is a very stable molecule, easy to formulate and has all of the kind of properties that you want from a drug molecule.
Now, I already touched on this earlier on, but one reason why we are so extremely excited about pimavanserin is, not only Parkinson's psychosis, which in itself represents a major market opportunity, but also the broader opportunity with pimavanserin in the neurology space.
We think that it should be relatively straightforward to leverage the PDP program into an Alzheimer's disease program for psychotic patients. And we already know from earlier FDA interactions that we can use the same safety population for an ADP filing as we use for the PDP filing.
The symptoms in Alzheimer's disease are similar to the symptoms in Parkinson's disease psychosis. And we expect to have those safety tolerability and efficacy in Alzheimer's psychosis as well. And of course, we don't only see ADP as of potential future indication for pimavanserin, but also Lewy body dementia psychosis and other neurological condition, which are poorly treated with off-label use of antipsychotics per day, that's why we expect that pimavanserin should be able to provide not only an effective, but also safe and well-tolerated therapy.
Alzheimer disease psychosis, it's a very large indication about 25% to 50% of Alzheimer's patients suffer from psychosis and we're talking about the huge population, over 5 million Alzheimer's patients in the U.S. alone. They are clearly not treated well with the off-label use of antipsychotics.
I already told you about the black box warning for these drugs. And we think that pimavanserin has the right profile for these patients. And we did in fact recently start a Phase II study to demonstrate that pimavanserin indeed is effective and safe and well-tolerated in these patients.
This is the study that is conducted at King's College in London, has a very interesting kind of structure. We are going to recruit about 200 patients in this study that will be randomized one-to-one between placebo and 40 milligrams of pimavanserin.
Although, it's one-center, its many more nursing homes. So the center is connected to about 100 nursing homes, which are research nursing homes, which means that the patients that we will study are well-defined, and we have their background well-established as well.
And because of the close geographical proximity of the nursing home, we will be able to assess the effect on psychosis and the other aspects of the study design using a small group of raters, who can move from side-to-side. And because we continue to use few raters, we expect a much better assessment, with less variability than you would get if you had many different assessors.
We use the brief psychosocial testing medium for this study as well. It's going to be a 12-week study, but the primary endpoint is at six weeks. It's the NPI, the nursing home scale that is used for measuring the effect on psychosis, but we also measure number of other aspects of these patients behavior using that scale. So we are going to look at the agitation, aggressiveness, irritability, anxiety, frequency used and quality of life aspects, et cetera, et cetera. We are also going to measure sleep in this study.
So we think that we will get a pretty good understanding of the global impact of pimavanserin on these patients through this Phase II study and we will then be able to enhance the design further when we move into Phase III from this study, which we expect currently to take about two years to completion from the start.
I've already talked to you briefly about the fact that we have conducted already a successful study in schizophrenia with pimavanserin. So what we decide to do in this study was to ensure that when we use pimavanserin together with the low sub-therapeutic dose of antipsychotic drug that you can fine tune the clinical profile of the drug.
This has really illustrated the better outcome. You can see on the left hand side, the efficacy of the low dose of risperidone, which is sub-therapeutic in yellow and the effect of a high-dose, a standard dose of risperidone in green, and what happens when you add 20 milligram of pimavanserin to the low dose of risperidone in blue, so we get exactly the same efficacy of the combination therapy as you would get of the 6 milligram dose of risperidone.
But importantly the side effect profile is significantly enhanced and that is demonstrated on the right hand side of this slide. You can see that the combination therapy reduces significantly less weight gain than the standard dose of risperidone, which is shown again in green.
We also see benefits on other side effects of risperidone, so we get less efficacia for example, than you see with the standard dose of risperidone. So in general, we get much improved side effect profile of this similar efficacy by combining pimavanserin with the low dose of risperidone and we expect similar kind of advantages by combining pimavanserin with other atypical antipsychotic drug that are currently used on health problems with a side effect profile.
This is an interesting study observation and we clearly want to follow-back on this. And although Parkinson's psychosis is our primary objective, Alzheimer psychosis is our secondary priority, schizophrenia is our third priority, and we will come back and inform you more about our thinking on schizophrenia next year.
So just let me summarize pimavanserin for you. We do think that we have a great drug profile with a very attractive safety and tolerability profile that has demonstrated strong psychosis efficacy in a Phase III study. And in the schizophrenia study and that they are currently conducting and Alzheimer's disease psychosis study to demonstrate the same kind of efficacy also in that population.
And we see a lot of different future opportunities with pimavanserin. Our current focus is very much on moving forward towards the NDA submission and we are very thankful, of course of having this expedited path to NDA submission, but behind that we are looking forward to also to addressing these other opportunities with pimavanserin.
Few words on ACADIA's profile. We are based in San Diego. We are small and virtually we are currently less than 50 people. And we have a strong cash position.
So with that, I thank you for your attention and would be open to any questions that you may have.
Boris Peaker - Oppenheimer
We have a few minutes for question, please wait for the microphone.
I have a question regarding pricing, in terms of how you're thinking about this given that Alzheimer disease is such a large population and Parkinson's disease psychosis is a much more often indication. How you're thinking about the pricing dynamics, when your first indication is going to be Parkinson, subsequently potentially Alzheimer's, which changed the perspective potentially of payers, et cetera?
It's a very interesting question. We think that pricing with drug like pimavanserin should be consistent to that of branded atypical antipsychotic drugs at least, that's a very reasonable consideration to make. Those branded atypical antipsychotics are priced well today, as you may be aware. And we don't see any reason why pricing of pimavanserin should be inferior to that.
And we are talking about completely new chemical entity, a new mechanism of action, the major unmet medical need. So we think that those arguments would really set the stage for a meaningful pricing of the drug. Of course, there were lot of work on ensuring that we get the pricing just right. And that is the one thing that our commercial teams will spend a lot of time in the next few months.
Could you comment on the side effect profile of pimavanserin, please?
Could you please repeat?
Could you comment on the side effects profile please?
The side effect profile is extremely attractive, I would say. If you compare the totality of side effects that we have seen with placebo-treated patients, with those patients that have been treated with pimavanserin, it's about the same. So it's completely different from the kind of the side effect profile that you see with the antipsychotic drugs that are used today. So the side effect profile and the efficacy together really shows that we have a completely different type of therapy that we can provide with pimavanserin compared to what you see with antipsychotic drugs.
Could you mention what are top two deleterious side effects that will be noted in a label?
Well, if I understand you correctly, you asked what side effects that could be in the label. So we have a dose limiting side effects that is observed at very high doses of pimavanserin. For example, in the early stage Phase I studies, we went up to 300 milligrams of pimavanserin.
And at those kind of doses, you'll start to feel nausea and emesis. At the dose that we are using in the clinic at 40 milligrams, we don't have a problem with that. So it's a very much placebo like. I think it's impossible to really speculate about anything that comes to the label of pimavanserin today, but what I can say is that we have a very attractive safety profile.
Boris Peaker - Oppenheimer
Thank you for your presentation.
Thanks, so much.
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