Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals First Quarter 2019 Financial Results Conference Call. My name is Shannon, and I will be your coordinator for today. At this time, all participants are in a listen only mode. We will be facilitating a question and answer session towards the end of today's call. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia.
Please proceed.
Thank you, Shannon. Good afternoon, and thank you for joining us on today's call to discuss Acadia's Q1 2019 financial results. Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide a brief overview of our strategy, recent achievements, pipeline opportunities and financial performance. Michael Yang, our Chief Commercial Officer, will provide updates on our commercial initiatives with Uplazid. Serge Sankovich, our President, who will discuss our pipeline progress and Alejda Ridloff, our Chief Financial Officer, who will discuss our financial results
before turning
it back to Steve for his final remarks and opening the call for questions. I would also like to point out that we are using supplement slides, which are available on the Events and Presentations section of our website. Before we proceed, I would first like to remind you that during our call today, we'll be making a number of forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward looking statements, including goals, expectations, plans, prospects, growth potential, timing of events or future results, are based on current information, assumptions and expectations These factors and other risks associated with our business can be found in our filings made with the SEC. You are cautioned not to place undue reliance
on these forward looking statements,
which are
made only as of today's date. I'll now turn the call over to
Steve Davis, our Chief Executive Officer.
Thank you, Mark. Good afternoon, everyone, and thank you for joining us today. During April, we and Acadia were proud to honor Parkinson's Awareness Month. This was an important opportunity for our employees to share their commitment to Parkinson's disease patients and caregivers whom we aim to serve every day. Many at Acadia participated in awareness and charity walks alongside patients and their caregivers.
In addition, we collaborated and pledged our support to several Parkinson's patient advocacy organizations across the country to help make educational events possible year round and not just during April. Please turn to Slide 6. We commenced 2019 with significant momentum executing on all three of our strategic pillars. First, we continue to grow the sales of NUPLAZID as the only FDA approved treatment for patients with Parkinson's disease psychosis. 2nd, we continue to leverage the potential of pimavanserin in additional indications with high unmet need.
And third, we continue to explore multiple opportunities to expand our pipeline through disciplined business development to achieve our long term vision in CNS. Let's review our Q1 progress on Slide 7. We are extremely pleased with our team's efforts this quarter driving our strong sales performance. In the Q1, NUPLAZID achieved $63,000,000 in net sales, a 29% year over year increase. Based on our execution and the growth of NUPLAZID in the Q1, we have raised the lower end of our revenue guidance and now forecast 2019 net sales to be between $280,000,000 $300,000,000 On the clinical development front, I'm pleased to announce that we recently completed enrollment in both of our late stage schizophrenia studies.
In our ENHANZE study, we're evaluating pimavanserin as an adjunct treatment in schizophrenia patients with an inadequate response and we expect to report top line data mid year. Our ADVANCE study is evaluating pimavanserin as an treatment in schizophrenia patients with prominent negative symptoms. And we now anticipate reporting top line results sooner than expected. We should have results from this study around the end of this year. I'm also thrilled to announce that we've recently initiated our Phase III CLARITY program, evaluating pimavanserin as an adjunctive treatment for major depressive disorder.
And finally, we expect to initiate our Phase 3 program evaluating trofinetide as a treatment for Rett syndrome in the Q4 of this year. With that, I will now turn it over to Michael to discuss our commercial performance.
Thank you, Steve. Please turn to Slide 9. Today, I would like to provide you with an update on the progress we are making in delivering continued growth of NUPLAZID. This has been the result of our execution of our key commercial initiatives to establish NUPLAZID as a treatment of choice in the management of PD Psychosis and we are pleased with the response we've seen from physicians, patients and their caregivers. We have successfully completed our transition to the 34 milligram capsule in the Q1 and have stopped selling the 17 milligram tablets.
We believe this will result in a more positive patient experience. NUPLAZID new patient starts in both the specialty pharmacy and the specialty distribution channels of our business continue to grow throughout the quarter. We believe this growth was due to the awareness built by our DTC campaign showing the potential positive benefits of NUPLAZID as a treatment for PDP patients. In February, we pointed out that the International Parkinson and Movement Disorder Society published their updated treatment recommendations for PD Psychosis, which included pimavanserin as the only medication listed as efficacious and clinically useful. Our team started educating about these recommendations in the Q1, which serve as important peer reviewed guidance on the appropriate care for patients with PD psychosis.
Physicians have told us that this guidance is useful to help support their treatment recommendations. Turning to Slide 10, as you can see, we have established a solid growth trajectory in 2019. We believe this reflects our continued growth in new patient starts and continued expansion of our prescriber base, driven by the response to our DTC campaign and our customer facing field force. Importantly, we continue to see more and more physicians use NUPLAZID as first line treatment for PDP. For the overall business, we achieved sequential volume growth of approximately 6.5% in the Q1.
We are especially pleased with the response our long term care specific commercial initiatives, which delivered a higher growth rate in long term care this quarter. We continue to receive feedback from the community about the positive experiences patients and their caregivers are having with NUPLAZID. We estimate that over 125,000 patients received treatment for PDP and we intend to continue to grow our market share in this population. The current growth supports our confidence in our updated 2019 guidance and the long term opportunity for NUPLAZID in PD Psychosis. I'll now turn it over to Serge to provide R and D updates on our pipeline.
Thank you, Michael. Today, I look forward to sharing some exciting updates regarding our R and D progress. Let's start with Slide 12. Pimavanserin is 1st in class selective serotonin invertegoes. All other antipsychotics were primarily by blocking dopamine, which is particularly problematic in Parkinson's patients who suffer from a lack of dopamine.
In addition to PDP, pimavanserin has already shown positive results in all four clinical categories we are currently evaluating in late stage clinical programs. We also plan to initiate a Phase 3 program for trofinetide in Rett syndrome later this year. In total, we are advancing 5 late stage programs. On Slide 13 are just a few recent highlights I wanted to share with you. 1st, as Steve noted, we recently completed enrollment in both of our late stage schizophrenia studies evaluating pimavanserin as an attractive treatment.
ENHANCE for patients with inadequate response to antipsychotic treatment and ADVANCE for patients with predominant negative symptoms. 2nd, we initiated our CLARITY Phase 3 program for pimavanserin as an adjunctive treatment for patients with major depressive disorder or MDD. And third, the positive Phase II results for trofinetide in Rett syndrome were recently published in Neurology. Starting with Slide 14, I will review our ongoing programs in a little more detail. There is no FDA approved treatment for dementia related psychosis or DRP.
DRP is estimated to affect approximately 2,400,000 patients in the United States, of which about half are diagnosed. Our Phase 3 HARMONY clinical study in DRP patients is leveraging the benefits we observed in 2 previous studies. Our PDP pivotal study as well as our Alzheimer's disease psychosis study. HARMONY is a relapse prevention study. As a reminder, all patients are treated with pimavanserin for 3 months in an off label fashion and only those patients with a stable response get randomized to either continue pimavanserin or to placebo and are followed for additional 6 months, primarily primary outcome is time to relapse.
We have agreement with the FDA that robust results for HARMONY can serve as the basis for a supplemental NDA submission. This development program received breakthrough therapy designation from the FDA, the 2nd such designation for pimavanserin. We anticipate final results of this study in 2020 with an interim read in the second half of this year. Let's turn to Slide 15 and our MDD program. Today, the standard of care for people with MDD is to initiate treatment with an SSRI or SNRI.
However, a majority of patients do not adequately respond to these initial treatments and continue to experience significant symptoms of depression. As a consequence, approximately 2,500,000 people in the United States take additional drugs as adjunctive therapy. Unfortunately for these patients, the approved treatments for both first line and adjunctive therapy in MDD can carry significant side effect burdens leading to high unmet need and sometimes difficult treatment decisions. We believe pimavanserin and its unique pharmacologic and clinical profile may represent an important new adjunctive therapy for patients struggling with MTD. Slide 16 highlights the results of our Phase 2 CLARITY trial compared to the significant unmet needs that exist today.
We had positive overall study results, including achieving statistical significance on our primary and key secondary endpoints relative to placebo. The results were even more remarkable in Stage 1. CLARITY results are impressive given the high unmet need that exists in the treatment of MDD. We believe these results are clinically important as we seek to develop pimavanserin as a potential adjunctive treatment for MDD. Slide 17 shows our Phase 3 development program for pimavanserin for adjunctive treatment of MDD, which we recently initiated.
CLARITY-two and CLARITY-three are both 6 week parallel design, randomized, double blind, placebo controlled, multicenter study designed to evaluate the efficacy and safety of pimavanserin as adjunctive treatment in patients with MDD who have an inadequate response to standard antidepressant therapy with either an SSRI or SNRI. CLARITY-two has initiated enrollment and will enroll approximately 280 patients in the United States. CLARITY-three will initiate enrollment in the coming months and will enroll approximately 280 patients outside of the United States. The primary endpoint in both studies is the change from baseline on the 17 item Hamilton Depression Rating Scale total score. Our Phase 2 CLARITY study combined with at least one of these Phase 3 trials could be the basis of supplemental NDA submission.
I'll now review our 2 schizophrenia programs starting on Slide 18. Approximately 1% of the adult U. S. Population suffers from schizophrenia and approximately 30% of those patients have an inadequate response to therapy, meaning they show some response to treatment, but remain highly symptomatic requiring additional therapy. With no FDA approved therapy for inadequate response, we believe the addressable U.
S. Population is roughly 700,000 patients. We have completed enrollment in our 6 week ENHANZE study and remain on track to announce top line data midyear. As a reminder, the primary endpoint in this study is a change from baseline on the positive and negative syndrome scale. On Slide 19, we have a graphic representation of the ENHANZE study design.
Turning to Slide 20. There is no FDA approved treatment for the negative symptoms of schizophrenia. Approximately 40% to 50% of schizophrenia patients experience predominant negative symptoms, which provide us with a potential U. S. Addressable population of approximately 1,000,000 patients.
Predominant negative symptoms include apathy, lack of emotion, social withdrawal and cognitive impairment. We have fully enrolled our 26 week ADVANCE study ahead of our expectations and now expect to announce results around year end. The primary endpoint is the change from baseline on the negative symptom assessment 16 item scale. On Slide 21, we have a graphic representation of the advanced study design. Turning to Rett syndrome and trofinetide on Slide 22.
Rett syndrome is a debilitating neurodevelopmental disorder that occurs predominantly females following apparent normal development for the 1st 6 months of life. Currently, there are no approved medicines for this rare disease, which affects approximately 6000 to 9000 patients in the United States. We plan to initiate Lavenger, our Phase 3 study for profinetide in Rett syndrome in the Q4 of this year. This 3 month study will evaluate approximately 180 females with Rett syndrome, age 5 to 20. If our Phase 3 trial is positive, there is a potential to submit an NDA in 2021 based on the single Phase 3 study.
Slide 24 provides a summary of our updated clinical milestones for 2019 beyond.
This is
an exciting time for Acadia in R and D and I look forward to updating you on our progress. I'll now turn the call over to Elena to discuss our financial performance.
Thank you, Serge. Today, I'll discuss our Q1 2019 results and financial outlook. Please turn to Slide 26. In the Q1 of 2019, we recorded $63,000,000 in net sales, an increase of $14,100,000 or approximately 29% growth compared to the $48,900,000 of net sales in the Q1 of 2018. This was driven by approximately 19% volume growth year over year.
The gross to net adjustment for Q1 2019 was 24.4%. The growth to net adjustment this quarter was less than our forecast, primarily due to stronger than anticipated performance in the specialty distribution portion of our business, which has more favorable growth to net. As a reminder, growth to net is typically highest in the Q1 due to the annual reset of the donor haul for Medicare Part D patients. Weeks of inventory in the channel at the end of the Q1 was consistent with year end 2018. Moving down the P and L, total operating expenses, including cost of goods sold, were $150,600,000 in the Q1 of 2019 compared to $103,700,000 for the same period in 2018.
These amounts included $19,900,000 $20,400,000 of non cash stock based compensation expense, respectively. GAAP R and D expenses increased to $52,900,000 in Q1 2019 from $39,300,000 in Q1 of 2018. The increase was primarily due to additional clinical study costs for pimavanserin as well as development costs for trofinetide. GAAP SG and A expenses increased to $93,100,000 in Q1 2019 from $60,900,000 in the Q1 of last year. The increase was primarily due to an increase in marketing expenses related to our DTC advertising campaign as well as increased charitable contribution.
Cash used in operations during the quarter was approximately $64,200,000 compared to $45,200,000 for the Q1 of 2018. We ended the quarter with $414,300,000 in cash and investments on our balance sheet. Please turn to our annual guidance on Slide 27. As Steve mentioned, for the full year 2019, we expect continued strong growth for NUPLAZID and have raised the lower end of the guidance range. We now forecast 2019 net sales to be between $280,000,000 $300,000,000 At the midpoint of this guidance range, this represents approximately 30% growth in revenue year over year and approximately 20% volume growth year over year.
We continue to expect gross to net adjustment in the range of 18% to 19% for the full year and forecast Q2 gross to net adjustment in the mid to high teens. Turning to expenses. We continue to forecast GAAP R and D expense to be between $250,000,000 $265,000,000 On a quarterly basis, R and D expense will step up starting in the Q2. This is related to the commencement of our Phase 3 program for major depressive disorder and manufacturing scale up to the trofinetide Phase 3 program. We continue to forecast GAAP SG and A expense to be between $280,000,000 $295,000,000 for the full year 2019.
On a quarterly basis, we expect SG and A expense to step down starting in the Q2. This is due to a reduction in advertising expenses related to the completion of our DTC campaign and reduced charitable contributions. We continue to expect non cash stock based compensation expense to be between $80,000,000 $90,000,000 in 20.19. And with that, I'll turn the call back over to Steve. Great.
Thank you, Elena. Please turn to Slide 29. In closing, our team is off to a great start executing on all three of our strategic pillars in 2019. 1st, growing NUPHISID in Parkinson's disease psychosis 2nd, leveraging pumavanserin in additional large market CNS indications and third, pursuing discipline business development. We truly appreciate the dedication and hard work of all of our employees who are driving our company's continued success.
I'll now open up the call for questions. Operator?
Your first question comes from Ritu Baral with Cowen.
Hi, guys. Thanks for taking the question. My first question is a little more detail on why you would discontinue the DTC or ramp that down given it seems to be working for you or is there an option to that going? Are you thinking about other commercialization strategies, I guess, to basically keep the renewed growth going? And I've got a follow-up on the negative symptom study.
Okay. Well, let's deal with DTC first. Michael, do you want to take that question?
Yes. Thanks, Ritu. I think our campaign, we had already always planned to have it run through the Q1, which we did execute that. And with campaigns like this, you create a bolus of attention and awareness and that is now going to flow through as people kind of go through the website because physicians which will be benefiting from that throughout the Q2 into the summer. It's very it's not normal to keep a campaign on 20 fourseven, 365.
So we'll be learning more along the way as we do the assessments. And again, the campaign just ended a few weeks ago. So now we'll be in the process of pulling that awareness through the physicians and generating that demand. So, we don't see a need to keep the campaign running throughout the year.
Got it. And then And
can we repeat any question?
Go ahead.
No, please go ahead. On negative symptoms?
Yes. And as we think about the upcoming Phase 2 data, on the PANSS negative symptoms scale, what constitutes good data? What constitutes the minimal clinically important difference? What's truly clinically meaningful to these patients? What would good data look like here, especially in comparison to the landscape?
Great. Serge, do
you want to take that question?
Just to clarify, Ritu, are you asking about the END study for inadequate response or you're asking about negatives predominantly negative symptom study?
Predominantly negative symptoms.
Okay. That one we'll be reading out later this year over
the year end.
We made for in the design of the study and the sizing of the study, we made assumptions that are very comparable to the effect sizes of a very few negative symptom trials that exist out there and that are considered clinically meaningful. We didn't disclose specifically what are the effect sizes we assume, but the negative symptom assessment scale has been used and is validated for this and we made certain assumptions in that regard that are clinically accepted as a meaningful endpoints.
What is that delta that you powered around?
Yes. Well, as I said, we didn't really disclose these. They are not disclosing the details as usually in our trials. But of course, we made appropriate clinically meaningful assumptions around that.
Got it. Thanks for taking the questions.
Sure. Your next question comes from Cory Kasimov with JPMorgan.
Hey, good afternoon, guys. Thanks for taking the question. I actually had a very my first one is similar to what Ritu was asking, but for the upcoming inadequate responder schizophrenia study this summer. And they're curious, I mean, I guess you're not going to disclose the exact effect size, but can you speak in at least general terms to kind of what you're looking for in the study, maybe the feedback you've gotten from KOLs on this front? And then my second trial probably would be for Serge as well as for MDD and CLARITY.
And I'm just kind of curious on your expectations for bringing sites online and the potential enrollment in these studies, I guess, especially the U. S. One first since that's already up and running. Is there anything you can glean on this front from all the other Phase III trials you've run with pimavanserin? Thanks.
Yes. Let me start with the ENHANZE study and the assumptions around that. With the inadequate response, our ENHANCE study, it's a little different because there is a plethora of studies and approved product in this. So there is a wide range of effect sizes that we saw with approved treatment in monotherapy or obese. And they range from starting somewhere 0.25 to 0.3 majority is between that and 0.5 effect size with only a few exceptions on the scale.
But we don't really, again, specifically discuss the deltas that we assume for the trial when we were sizing the trial. I just want to make one more comment here and that is this is an adjunctive treatment and there are no other treatments for adjunctive therapy. So all of the assumptions around this are related to the monotherapy trials in schizophrenia. MDG? With regard to MDD, obviously, in the U.
S. Trial, we had a benefit of the number of sites that we worked on our CLARITY trial in the Phase II trial. So we in terms of engaging the sites, there was quite a bit of interest. And with the positive results, we had quite a bit of interest for participation of the trial. So from that perspective, recruitment of study sites to participate was a very smooth process.
We expect ultimately that recruitment will be going fairly similarly like we had in our CLARITY trial and that was even probably a little bit better because of now with the positive results, there is higher level of interest obviously on the public. Compared to other primavanserin trial, as you asked that as well, I mean, we I have to say, we had a fairly smooth recruitment across our different indications in all of the trial and it is reflected in the way how we were able to follow our projected timelines for recruitment. So depression is no exception to that.
Can you just remind us how long it took you to recruit the Phase II CLARITY trial?
It was a little more than 2 years. So we are expecting in this trial that there will be a similar situation about 2 to 2.5 years to complete the trial.
Okay. Thank you.
Your next question comes from Jason Butler with JMP Securities.
Hi, thanks for taking the question. First one on the commercial and another follow-up on the DTC. Can you maybe frame for us that bolus you mentioned before and how it compares to the impact or the positive impacts you got from the DTC campaign this time last year?
Yes. Jason, I'm sorry, just want to make sure we're clear on the question. The bolus you're referring to is what?
So the bolus of patient inflow into the you mentioned in answer to a previous question that you got out of the DTC campaign this year versus last year that you're now in the process with this year going through and looking to pull patients through on therapy?
Got it. Okay. Yes, I don't think we use the herbals, but I get the question and I think Michael does too.
So Michael, you want to
write it down? Yes. Thanks for the question. So in let me address the second part first. The first campaign that we did a year ago was disease awareness.
And of course, this is a branded campaign. So I think it's very hard to compare the 2 in regards to impact. In fact, we believe we're obviously getting a better brand request rate and interest rate with the branded campaign. In regards to the and what I was referring to is that we generate a lot of awareness and interest with the campaign. That's really what the original the first phase of the campaign is designed to do, stimulate interest and awareness.
What we're now seeing is a very healthy attention rate into our digital properties, websites, etcetera. So we're getting good engagement there. We're also hearing both anecdotally and starting to track some data at the doctor level. Those patients that are in that process will become after they go on an appropriate trial, paid patients and generate revenue in ensuing quarters. So that's why we phased the campaign in the beginning of the year, so we'll get the benefits of that throughout 2019.
Maybe just a little bit of additional color there. I think on the last earnings call, we kind of walked through kind of the process of patients becoming aware of the drug. They Parkinson's patients typically see their doctor every 3 months, sometimes every 6 months, sometimes a little more frequently. So many times there's repetition of messaging to create awareness. Then they have an appointment some months later, and then we start the process of them getting a prescription and going through a free drug and then a paid drug.
And then it's a full quarter after beyond all of that that you get the full benefit of full quarter revenue from a patient that you started by increasing awareness. So I think the point Michael was making earlier is the work that we've done in DTC over the last several months, we'll expect the benefit of that to continue on for some period of time. Great. Okay.
And then just one question on the negative symptoms trials. Can you just talk about the background positive symptoms score you expect to enroll in the study? And what happens? Is there anything built into the protocol if a patient has worsening positive symptoms at any point during the trial?
Sure. Soren, do you
want to take that question?
Right. We in the negative symptom study, there is a requirement that the positive symptoms are fairly well controlled for the patient to be able. So it's predominantly negative symptom studies. So the positive symptoms are kept at a certain minimum of severity to be able to enroll in the study. In terms of potential worsening of positive symptoms, obviously, it's a clinical decision by the physician investigator whether they want to discontinue the trial and apply change in patients' therapy.
It's not something that we in the trial so frequently or there is something that we anticipate to happen because patients are continuing on their background antipsychotic. So if they have a good control of positive symptoms, but still express negative symptoms, that should be continuing throughout the trial. And for the most part, that's what we are seeing.
Okay, great. Thanks for taking the questions.
Your next question comes from Salveen Richter with Goldman Sachs.
Thanks for taking my questions. So in the Phase 2 schizophrenia trial, you used NUPLAZID and risperidone and you saw some benefits in PAN score and positive and negative symptom subscales. But your patient demographic wasn't specifically inadequate responders or negative symptom patients. So how should we think about the read through here to these two patient demographics?
Hey, Salveen. Yes, that's you're correct. The paradigm in that study was somewhat different. In that study, we use sub therapeutic doses of risperidone. In other words, a 2 milligram risperidone versus therapeutic dose of 6 milligram risperidone and combined it with pimavanserin, while 6 milligram risperidone was alone.
And what we saw is that the efficacy that we saw in that trial was comparable and in some aspects a little bit better than what we saw with the full therapeutic dose of risperidone risperidone and improvement on the tolerability side of that trial. So we obviously, in that trial, demonstrated synergies between atypical antipsychotic risperidone with pimavanserin. What we are looking in this trial is a little different paradigm, obviously, people that are on atypical antipsychotic, but don't have a full response. And we are still looking for that synergistic effect to enhance the efficacy of the adjunctive treatment. So hence, the name in HEMCE.
Got it. And then maybe just a second question on your commentary that DTC didn't provide much benefit to the long term care setting. Are there other strategies other than awareness that could be undertaken here?
So, Kevin, I'm going to ask Michael and you want to just first clarify the point here.
Hi, Salveen. Yes, no, I don't believe that I said that we did not see an impact in LTC. Maybe you misheard that. What I mentioned is when we did the first campaign to compare the first campaign, which was disease awareness to the branded campaign, there are different dynamics. And a point in fact, actually what we're seeing is an unexpected benefit from the branded campaign in long term care.
We believe that was part of the wind in our sales in long term care in the Q1. And conversely, we did not see that benefit specifically in long term care with our disease awareness campaign. So we are seeing benefits now whether that is sustained over time, we'll be evaluating that, but we're very pleased with that impact that we saw in long term care with our disease, with our branded campaign that we have on air just finished.
And I'm sorry, just to be crystal clear, disease awareness campaign run a year ago Correct.
Did not see much of
an impact on long term care. Branded ad, we just finished this year, we didn't need
to buy. That's correct.
Thank you.
Your next question comes from Tazeen Ahmad with Bank of America Merrill Lynch. Hi, Steve. Just wanted to ask you a question with regards to guidance. So, on the call so far, you've stated that you feel good enough with DTC that you're ready to wind that down a bit and focus on all the leads that you have. I think you also mentioned you've had an uptick in long term care.
So I guess what more would you need to see in order to raise the higher end of guidance as well as the lower end? And then I have a follow-up.
Thanks for the question, Tazeen. I'm going to let Elena answer the question.
Thanks, Tazeen. So as we discussed year over year in the Q1, we had 19% volume growth at the midpoint of our guidance. That's pretty for the full year, that's pretty much on track with what's included in the midpoint of our guidance. So at this point in the year, we feel very pleased with how increased the low end of the range. As Michael mentioned, we have a number of commercial initiatives and are pleased with what we're seeing so far with DTC, and we'll continue to track that and how we're tracking versus our full year guidance.
And if appropriate, we will adjust in the future.
So just to clarify go ahead.
I was just going to
say, just to be clear, as we mentioned earlier, on the DTC campaign, it's not that we stopped it because we've seen a certain result. We ran the campaign exactly as planned. So ran it through the planned conclusion of the television, television, television, television, television, but we expect benefits to run beyond that. And you do reach a point where of saturation where you do need to actually stop the television campaign in order to get the full benefit. So we feel really good about the early returns that we have on the campaign at this point.
And then can you just give a little bit more color on your free drug program? How long does it last and how many times can a patient renew? Has that changed?
Sure, Michael.
Yes. So the standard program is a 14 day free trial when they come through hub and distribution services. And they can re up for that for another 14 day if the patient needs it. So we're not we don't hold that as a hard rule, but if someone needs an extra 14 days to get it. The majority of patients get 14 days.
And the use of that program, has that stayed stable or has that changed?
It's been pretty stable.
Okay. Thanks. Your next question comes from Charles Duncan with Cantor
Fitzgerald. Hi, guys. First of all, congrats on good quarter progress and thanks for taking my questions. I had 2, 1 commercial and one pipeline. The first regarding commercial, you had some comments on long term care and the growth and you talked about the positive impact of DTC at least initially.
I'm wondering what else is contributing to the long term care growth rate that was a little higher than you expected. And perhaps if you could touch on persistence now with the 34 milligram tablet versus the 2x17?
Sure, Michael. Sure. Thanks, Charles. Appreciate that. We were very pleased with what we saw in both long term care and RSP.
So I want to be clear, we were very pleased with the bottle demand, the unit demand in long term care and our new to brand growth in our specialty pharmacy channel. Specifically, in addition to what I mentioned around the benefit of awareness through the campaign in long term care, I think what you're starting to see is really a continued maturation of our long term care commercial capabilities that has helped us drive growth in this setting. Basically, what we're doing is focusing on generating deeper demand in accounts and systems where we have set up deposit access at the pharmacy. We've identified and nurtured a PDP disease champion. And then we further followed that up with a patient identification process and that's a system by system account system that we have.
So that started to pay off dividends with our commercial execution. That is in part also aided by the awareness driven by the DTC campaign and that's what you're starting to see I think pay off in long term care.
Okay. And then my thanks Michael for that. And then my second question is perhaps for Serge. On the pipeline and specifically ENHANCE versus ADVANCE. And several questions have been asked on design and effect size assumptions, etcetera.
But wanted to step back and just ask you, when you think about the unmet need in terms of inadequate response versus negative symptoms, You laid out the number of patients, but where do you think the potential is to make a greater clinical impact on patient care and therefore perhaps even pharmacoeconomic value of the 2 indications?
Yes. I'm sorry, Serge.
Thanks, Charles. That's a great question actually and one that provokes a lot of thinking on the one interesting point I wanted to make here at the beginning is that both of these trials are adjunctive trial. And currently, there is no any antipsychotic approved for adjunctive treatment in schizophrenia. Now it is true that in the ENHANCE trial, we are using patients that have symptomatology both in the on a positive and a negative syndrome scale, while in the ADVANCE trial, we are more focusing highly great. There is nothing that truly demonstrated efficacy in treating negative symptoms of schizophrenia.
And from that perspective, it would be a great advancement in medical practice if we demonstrate a benefit in that adjunctive paradigm. But I would also say that on the adjunctive treatment of schizophrenia in general, even though there is nothing approved, there is a great many patients that are treating with 2 or more anti psychotics at the same time because one anti psychotic is not able to control psychotic symptoms. And from that perspective, numbers vary widely, but they go from 25% to 65% of patients that are on the 2 antipsychotics or more at the same time. So from that perspective, looking at that, it would be a great advantage and advancement if we demonstrate positive efficacy, benefit and safety for adjunctive treatment rather than using the antipsychotics that more or less are hitting on the same receptors and on the same neurotransmitters. And therefore, even if they're producing some benefit, they're also producing a myriad of side effects and tolerability issues that we do not expect to see.
I hope this is just a kind of a brainstorming here. It's a very interesting question, and I would like to talk more when I see you about this.
That sounds good. I just sorry for a clarification request and that is that and appreciate you taking it is, Advance seemed to enroll perhaps a little quicker than we had expected. And I'm just kind of wondering, are physicians equally or more or less interested in enrolling 1 or the other study, if you have them on both?
In the last maybe several months, ADVANCE sort of caught up with
the ENHANZE
study, and they essentially finished recruitment approximately at the same time. I wouldn't say that that's a reflection of as much interest, as much dynamics in the clinical trials out there and competitive environment, countries where we are doing the trials. There are many factors that influence that. And perhaps there is also an interest, I wouldn't discount that, But I don't think that that's the only factor that contributed to us. We always expected that these two trials would actually progress in the same time.
The delay on the ADVANCE trial is just because it's a 6 month trial versus 6 weeks trial. So the readout will be 6 months later.
Got it. Thanks for taking the questions. Congrats on good quarter.
Your next question comes from Alan Carr with Needham and Company.
Hi. Thanks for taking my questions. A bit of a follow-up on previous one around ADVANCE and ENHANCE. Are you all disclosing which background meds are being used most often, which antipsychotics are being used most often at baseline in those two trials? And then with respect to ADVANCE in particular, is there any sort of run-in period to ensure that there is stability on positive symptoms?
The last one is around charitable contributions, wondering if you can comment on that. And I think you said there would be reductions in that. And can you elaborate? Thanks.
Thanks, Sudhak. Do you want to take the first two questions? Yes.
In regard to remind me where it was the first part.
The background meds.
Background meds, yes.
Just any psychotic. Just any psychotic.
Saying that there is no secret about that. All atypical antipsychotics that do not have a warning related to QT prolongation are allowed in our trials. So the only reason we excluded some of the antipsychotic was because of QT prolongation and our label and their label indicated that combination with other drugs that prolong QT is not allowed. So from that perspective, all we should consider all atypical antipsychotics. So there is no secret about that.
I was wondering if you all are disclosing which specific drugs do any of them dominate in terms of the patients that you enrolled in the trial? Well,
we didn't of course, we will review that at the time of top line results, but we have a fair representation of the antipsychotic. This obviously somewhat depend also on the countries where we are. In some countries, there are different drugs approved and not approved. But naturally, I mean, the most this follows fairly accurately what is the use of these antipsychotics out there. So the most frequently used antipsychotics is the most that we see in our trials.
But we didn't go into specifics on in that regard.
Okay. And a run-in in advance, is there anything like that to see
a PR? Well, we first of all, there is a run-in period. There is a screening period where we evaluate patients at a qualification of the trial at the screening phase and then at a baseline visit and they do need to meet same criteria for entering in the trial over that period that may go up to 3, 4 weeks. So that's one thing that but additionally, we are also very careful in selecting the patients to make sure that they have levels of background antipsychotic in their blood to confirm that actually symptoms we are seeing are results and in spite of background antipsychotic therapy that's particularly relevant or that's relevant for both of these trials. So we are in some sense looking both at the stability and the symptoms we are seeing are results of inadequacy in therapy rather than non compliance with treatment.
Okay.
Charitable contributions, you asked about as well, Alan. Elena, do you want to take that question?
Sure. So Alan, contributing to independent charitable foundations that provide assistance to patients in need is part of our commitment to help sure patients have access to their prescribed medications and treatments. For 2019, a greater portion of those donations are occurring in the Q1 of the year.
Okay. Thanks for taking my questions.
Your next question comes from Danielle Brill with Piper Jaffray.
Hi, everyone. Thanks for taking my question. I just had a quick question on the usage of NUPLAZID and more specific question on channel distribution. Would you be able to provide some color on what percentage of patients with PDP are actually on UPLAZID? I think you mentioned that it was 25% previously.
I'm going to let Michael answer you want to first clarify what we said previously.
Yes. We've previously said that there are 125,000 patients treated and our penetration is around the low double digits. Currently, we're, I would say, in the mid teens in that regard. So that's where I would answer the question.
I see. Great. Okay. And I guess the other question I had was, would you be able to provide some color on the volume growth trends between specialty and LTC and which channels are growing faster if specialty has caught up? Any sort of color would be helpful.
Yes.
Great question. So I think that we've always represented that the SB, Specialty Distribution, of which long term care is about 2 thirds of that component has roughly been about 1 third of our business. The SD part of our business is 1 third and our SP side which represents more of the office based channel is about 2 thirds. And that makes it generally pretty much where it's been, it waxes and wanes depending on different dynamics. The way just the way to think about it is the way we see it, which is they're independent channels.
They have different dynamics, different ecosystems and things kind of wax and wane. One other thing to note though is in the long term care channel specifically, we've always said that we're a little under penetrated and that has a more volume growth ahead of it because we were we just recognize that that's a more rich channel that we didn't launch that with kind of robust efforts at the beginning. So as you know, we expanded our sales force and we have continued to evolve our commercial model there. So we're getting good results out of that, but SP is also going to be growing as well. So both channels have a lot of opportunity to grow, 1 third, 2 thirds would be the split.
Fantastic. Thank you so much.
Your next question comes from Mark Goodman with Leerink.
Yes, hi. Can you talk about business development a little bit? Should we expect another trofinetide type of opportunity to get added to the pipeline this year?
Yes, sure. So as we said very clearly on this call and on many previous calls, business development is one of our 3 strategic pillars. We think it's very important that we focus on that in a disciplined way, the disciplined way that we have. And trofinetide is a really great example of the kind of fruits that we expect to continue to yield from that process.
Well, maybe just ask the question in a different way. I guess trofinetide was practically Phase 3 ready, right? So I was curious about as you're thinking about early phase, late phase, what are you looking at? How should we expect you to bring products in from that perspective?
Yes. So just as a matter of follow-up, we don't get into too much detail regarding specific assets or specific categories. We do have priorities, but we don't always talk specifically about them. I would just simply say, I think every asset is case dependent. Of course late stage assets have a different risk reward profile than earlier stage assets.
And just if it's helpful for just some additional color, I would say when we launched NUPLANEXX or before we launched NUPLANEX, we did a survey when new companies that launched their first drug acquire additional assets. And what we saw is a very small blip on
the radar screen at about year
3 and then a
big blip at about year 7. And that just didn't get any reason to wait. I'd rather look at more assets over a longer period of time so it can be more judicious and more strategic, and that's what we're doing.
Thanks.
Your next question comes from Paul Matteis with Stifel. Your line is open.
Great, thanks. This is Ben Bernatte on for Paul Matteis. I wanted to ask just a clarifying question on the regulatory path for schizophrenia. I guess if both schizophrenia studies are positive, the negative symptom study and the inadequate response study, would you expect this to be enough to file on for both indications, I. E.
Like would you be able to include negative symptoms in that or would you anticipate needing additional confirmatory studies? And then I just have one real quick follow-up.
Sure. Zuri, do
you want to take that question?
Yes. What we know, similarly as with major depression, the regulatory requirement for approval in adequate response would be 2 confirmatory trials. We, of course, are looking at variety of options, but it is just premature for us until we see the results of the trial to speculate on potential regulatory path for approval. And we will certainly once we have the results, we will certainly address that and address that with FDA as well.
Okay, great. Understood. And I just had one other question on the DRP HARMONY program. I guess at this point, what proportion of patients are you seeing get through the treatment run-in in the study? And if you're willing to disclose this or if you can, I guess, how is this comparing to your expectations going into it?
Right. I can say what I which I shared before and that's pretty much continuing and that is that we are seeing in the 3 month open label treatment phase of the study that somewhat some a bit larger number of patients are achieving stable stabilization over 2 8 week 12 week period and are being randomized that we initially anticipated. So other than that, we did not disclose specific numbers, but I can say we made these assumptions on a basis what we saw in previous trials with pimavanserin and are seeing around that or
a little bit better than that. Okay.
I appreciate the color. Thank you.
Your next question comes from Sumant Kulkarni with Canaccord.
Good afternoon. Thanks for taking my questions. I have a couple. The first one, we have an important interim read in the dementia related psychosis harmony trial coming up later this year. But my question is on your SERENE trial in Alzheimer's related agitation.
We know the trial was discontinued in October 2017, but patients enrolled in that study were allowed to continue. Given Serene is now showing up as completed as of late March according to clinicaltrials dotgov, Do you plan to share any data there? Or how should we think about your expectations heading into the interim read on Harmony?
Bert, did
you hear
the question? Yes.
I assume that. Well, what we shared the data from that trial on the as it is required in the clinicaltrial dotgov with the results from that trial. And obviously, we will, as necessary As we see fit, we will further share the information and data. That's a trial that was stopped for business reasons at the point where we were moving into DRP, so it's incomplete trial. But there are some learnings that we really applied as we move forward with the trial.
So the core of the data is already available publicly.
Sure. Thanks for that.
And the second question is on your Rett syndrome trial. How do you expect enrollment in that trial relative to potential competition from other approaches like gene therapies that might be coming up?
Right. Yes, Serge, do you want to take that question?
Well, naturally, we are following all of the developments in the Rett syndrome. Specifically to your question, gene therapy is a little bit behind and it's probably going to take a little more time for them to actually get into the clinical stage. So from the competitive perspective in terms of the execution of our Phase III trial, I do not see that, that will interfere. Now there may be other trials in Rett syndrome, some addressing specifically specific symptoms of Rett rather than the core symptomatology of Rett syndrome that may be going on, but we don't see that will be a significant overlap. I have to say that we are working very closely with advocacy groups and understand that there is quite a bit of interest on the basis of positive data from the Phase II trial in participation in our trials.
So we do not anticipate a significant competitive pressures on recruitment.
Thank you.
Thank you. Mr. Davis, please proceed to closing remarks.
Great. Thank you, operator. Just want to close by saying thanks to each of you for joining us today. And we look forward to updating you on our progress next quarter.
Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.