Earnings Call Transcript
ACADIA PHARMACEUTICALS INC (ACAD)
Earnings Call Transcript - ACAD Q3 2021
Operator, Operator
Good day, ladies and gentlemen. And welcome to the ACADIA Pharmaceuticals Third Quarter 2021 Financial Results Conference Call. My name is Gigi and I'll be your coordinator for today. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia. Please proceed.
Mark Johnson, Vice President of Investor Relations
Today's call is to discuss ACADIA's third quarter 2021 financial results. Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide an overview of our Q3 2021 financial performance and a review of our business operations. Also joining us today is Brendan Teehan, our Chief Operating Officer and Head of Commercial, who will provide updates on our commercial performance. Dr. Srdjan Stankovic, our President, will discuss our pipeline progress and our Interim Chief Financial Officer, Mark Schneyer, will then discuss our financial results in more detail before turning it back to Steve for final remarks and opening the call for your questions. I would also like to point out that we're using supplemental slides which are available on the Events and Presentation 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 for future results are based on current information, assumptions, and expectations, that are rather subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially. 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 will now turn the call over to Steve.
Stephen Davis, CEO
Thank you, Mark. Good afternoon, everyone and thanks for joining us today. I'd like to start with a quick recap of our commercial performance, followed by a regulatory update for Pimavanserin and a preview of our coming catalysts. Please turn to slide 4. First, I'd like to take a moment to remind everyone of our announcement last week that Brendan Teehan has been promoted to the position of Chief Operating Officer and Head of Commercial. Brendan has been a tremendous leader for our team, and I'm very excited to be able to further leverage his deep experience and strong capabilities. While Brendan will take you through our commercial update in greater detail in a minute, let me just say that on a macro level, the Parkinson's disease market continues to be significantly impacted as a result of the pandemic. Despite these challenges, NUPLAZID has outperformed branded drugs in the space, and for the third quarter of 2021, NUPLAZID achieved $131.6 million in net sales. This represents a 9% year-over-year increase with sequential and year-over-year volume growth. As shown in the graph on the left, our team has continued to execute with year-over-year and sequential growth each quarter since the beginning of the year. To be more precise, NUPLAZID has outperformed the market basket of top prescribed brands in urology and Parkinson's disease in the office-based setting. Similarly, NUPLAZID has continued to show strong performance in the long-term care channel. Our strong relative performance underscores our team's ability to adapt and find ways to grow our brand. This includes our recently launched branded campaign targeting healthcare providers, which promotes and highlights its unique safety profile specifically as it relates to the Parkinson's community. On the patient and caregiver front, we're in the process of launching a new DTC campaign aimed at solving one of our biggest COVID-related challenges, which is physicians not seeing as many PDP patients in person. As such, this DTC campaign is aimed at patients and caregivers who are at home, and it's designed to activate them to have a conversation with their doctor about their symptoms of psychosis and potential treatment with NUPLAZID. Our growth initiatives, new leadership, and strong relative performance give us confidence that we will further accelerate the growth of NUPLAZID into 2022. Now let's move to our regulatory update regarding our sNDA for Pimavanserin on slide 5. As you recall at our top 8 end of review meeting, the FDA made it clear that today they are looking at individual subgroups of dementia rather than DRP as a single group. Accordingly, they stated that they believe our best path forward is to conduct an additional study in each subgroup where we seek approval. However, at that meeting, the FDA also stated that based on additional analysis we've shared with them, they are open to having another meeting to discuss whether there is a potential path to resubmission without an additional clinical study in any of the subgroups. This meeting is now scheduled, and we expect to be able to report on the results of the meeting around year-end. When we look at our dementia subgroup data, it's very clear that we have the most data for Alzheimer's disease, which represents somewhere between 60% and 80% of all dementia patients in the U.S. Our database includes two independent clinical studies providing evidence of Pimavanserin's anti-psychotic efficacy in Alzheimer's disease psychosis, study O19 and the HARMONY study. Together, these studies demonstrate improvement in psychotic symptoms and reduction of risk of relapse of psychosis in ADP patients. At our upcoming meeting with the FDA, we look forward to sharing additional analyses we've done in response to the feedback from the last meeting. Serge will provide more details on this opportunity in his section. As we look ahead, I'd like to highlight some important near-term catalysts as shown on slide 6. First, as noted, we look forward to providing an update from our meeting with the FDA around year-end. Second, we expect to announce top-line results from LAVENDER, our pivotal Phase III study for trofinetide in Rett Syndrome later this quarter. And third, we expect to announce top-line results from a Phase 2 proof-of-concept study evaluating ACP-044 in post-operative pain following bunionectomy surgery in the first quarter of 2022. Finally, our company is well poised for further expansion. We have a healthy balance sheet, a growing revenue base, and best-in-class in-house R&D and commercial teams. Business development continues to be a key priority of our strategy, and we continue to be very active on that front. I would now like to turn the call over to Brendan to discuss our commercial performance.
Brendan Teehan, CFO
Thank you, Steve. Today I'd like to review our third quarter performance for NUPLAZID in Parkinson's disease psychosis. Please turn to slide 8. In the quarter, we delivered net sales of $131.6 million. This quarterly performance represents a sequential demand growth fueled by new patient starts and continuing patients with strong adherence and compliance rates. I'd like to start with a deeper dive into the current macro environment that we're operating in. As we've stated previously, the pandemic has disproportionately affected the Parkinson's disease patient population, significantly impacting the market. As shown on the slide, PD office visits and occupancy rates at long-term care facilities are still down significantly from pre-pandemic levels. Despite this, NUPLAZID has continued to grow meaningfully throughout the period with strong relative performance compared to the overall Parkinson's disease and broader neurology markets. More specifically, when we compare recent quarterly performance with pre-pandemic performance of 2019, we see the following. In the office-based setting, carbidopa and levodopa are down 4%, and the top 10 Parkinson's brands, on average, are down 7% over that time period. And while the top 15 marketed neurology products are up 15%, NUPLAZID is up fully 28% for that same time period. Similarly, in the long-term care channel, Carbidopa and Levodopa are down 12%, and the top 15 LTC brands are down on average 22%, while NUPLAZID has grown 8%. Perhaps the most important of all these data points is the Carbidopa and Levodopa's total prescription trend. These are the fundamental PD movement disorder medications, and they have trended down during the pandemic. This decline clearly signifies just how challenged the PD market has been over the past two years. However, against the backdrop of this environment, NUPLAZID has continued to grow in both channels, giving us confidence in our future growth. We've had to adapt, and by utilizing novel analytics and the thoughtful implementation of our tactics, we have found new opportunities to grow new patient starts. Our strong relative performance and continued growth across all channels underscore our commercial execution and give us confidence that our tactics are working and will continue resonating in the months ahead. Furthermore, our team is not simply waiting around for the macro environment to improve. We are buckling down and working even harder to ensure that we are interacting with and educating physicians, patients, and their caregivers on PD psychosis and treatment with NUPLAZID. Let's turn to Slide 9 to continue the discussion on what we're doing to further grow the brand. To continue to drive brand choice and growth in the second half of the year, we have introduced two new important campaigns. One focused principally on the healthcare provider or HCP audience, and the other focused on engaging patients and caregivers. On this slide, I'd like to discuss our new HCP-focused messaging platform that educates the treating community on the unique safety profile of NUPLAZID, specifically as it relates to the Parkinson's community. Our campaign is amplified across all promotional channels, including our field teams, and is resonating well with HCPs. This messaging incorporates market research insights focused on HCPs' treatment goals for Parkinson's patients experiencing psychosis and specifically on NUPLAZID's safety and tolerability profile in light of other important medical considerations, the most notable being the desire to avoid impacting motor function. Our messaging demonstrates a deep understanding of our clinicians' treatment goals by leveraging important clinical data to better educate physicians on NUPLAZID's safety and efficacy profile. While early in the rollout of this campaign, this messaging is resonating with physicians, and we see the opportunity to further increase diagnosis and capture a higher percentage of new PDP patients for NUPLAZID moving forward. Slide 10 highlights our new direct-to-consumer campaign, which is intended to reach patients and caregivers at home and drive them to their physicians to have conversations about their symptoms of psychosis and treatment with NUPLAZID. This campaign should help solve one of our biggest COVID-related challenges: patients staying at home and not seeing their physicians in-person, and therefore not adequately discussing their symptoms or new treatment options. Our campaign has been on air since mid-October. It tells an important patient caregiver-centered story about the impact of PD psychosis. The ad introduces NUPLAZID and its potential treatment benefits to both patients and their families. The ad also includes a critical component of disease awareness to help patients understand and recognize the signs and symptoms and prevalence of psychosis in patients living with Parkinson's disease. With the work our commercial team has been doing, executing on the new messaging platform on the HCP side, this is the perfect time to introduce a new patient-centric campaign, drive new patients to their newly educated doctors, and grow the NUPLAZID brand. Of course, while we expect to see traction in the fourth quarter, the full benefit of these complementary campaigns will be mostly realized in next year's growth. The bottom line is that patients and caregivers are in need of better treatment options such as NUPLAZID, and patients and caregivers need to recognize the symptoms of psychosis and its connection to Parkinson's disease. We are confident our campaigns will accomplish this. I will now turn it over to Serge.
Serge Stankovic, President
Thank you, Brendan, and good afternoon everyone. As Steve mentioned, we have had a constructive dialogue with the FDA and are looking forward to our upcoming meeting. While we continue to believe that evaluating Pimavanserin as a treatment for the broad dementia-related psychosis indication is most appropriate, we understand the FDA's position and are preparing additional analyses to support Pimavanserin as a potential treatment by dementia subgroup. Let's start the discussion on Slide 12 with an overview of our HARMONY data, specifically looking at the Alzheimer's disease subgroup, which, as Steve mentioned, is the most prevalent form of dementia. On the left side of the slide is an overview of Pimavanserin's anti-psychotic efficacy observed overall, and in the Alzheimer's disease subgroup in the open-label portion of the HARMONY study, as well as the primary efficacy outcome in the double-blind portion. As we previously noted, HARMONY was not powered to show statistical significance by dementia subgroup. However, we did prospectively plan exploratory efficacy analysis of dementia subgroups. In the Alzheimer's disease subgroup, we see that Alzheimer's disease subjects who remained on Pimavanserin were about 40% less likely to experience a relapse of psychotic symptoms compared with those on placebo, as shown with a hazard ratio of 0.62. Post-hoc analysis of the Pimavanserin 34 milligram dose group, the dose currently approved for treating PDP patients, showed about 50% risk reduction with a hazard ratio of 0.47. For context, this magnitude of effect is in line with what has been observed in numerous relapse prevention studies of comparable design for approved drugs in various psychiatric indications, such as schizophrenia or depression. In addition, this benefit is further supported by a number of complementary analyses, some examples of which are listed on the right-hand side of this slide. These analyses consistently show the antipsychotic efficacy across different endpoints within the Alzheimer disease subgroup, which clearly supports the overall conclusion of the clinically meaningful benefit that Pimavanserin demonstrated in the treatment of psychosis in Alzheimer patients. Furthermore, these additional analyses also demonstrate and confirm Pimavanserin's observed antipsychotic treatment effect across all dementia subgroups and thus provide further supportive evidence for the benefits of Pimavanserin in Alzheimer's disease psychosis. Please turn to slide 13. In the upcoming meeting, we will also discuss our positive 019 Study, a randomized placebo-controlled study of Pimavanserin for the treatment of symptoms of psychosis in Alzheimer's disease patients. The primary efficacy outcome was positive with a p-value equal to 0.045 in a pre-specified analysis of Alzheimer's disease subjects with more severe psychotic symptoms; the magnitude of efficacy more than doubled with a p-value equal to 0.011. In response to issues raised in the complete response letter, ACADIA has conducted multiple sensitivity and responder analyses that support the primary efficacy conclusion. Note that the responder analysis shown on the right of the slide also demonstrates that Pimavanserin had even greater efficacy in those patients with higher severity of psychosis. To recap, Pimavanserin has been evaluated in ADP patients across two independent clinical studies and, in addition to positive and clinically meaningful efficacy, has been well tolerated and, importantly, has not shown negative impact on cognition or motor function. In our next meeting with the FDA, we will share several analyses and a substantial data set demonstrating the potential utility of Pimavanserin in the treatment of ADP in order to further examine the potential for resubmission without conducting additional clinical studies. Now, I would like to discuss our pivotal Phase 3 study evaluating Trofinetide as a potential treatment for Rett syndrome. On Slide 14, LAVENDER is a randomized double-blind placebo-controlled study in approximately 180 young females ages 5 to 20 with Rett syndrome. Patients are evaluated for 12 weeks. The co-primary endpoints are the Rett syndrome behavioral questionnaire, or RSBQ, a caregiver assessment tool; and the clinical global impression of improvement, or CGI-I, which is a physician assessment. We are currently on track to announce top-line results by year-end. Importantly, we have agreement with the FDA that positive results from LAVENDER, in addition to supportive efficacy data from the previous Phase II study, and the safety database we are collecting could be sufficient to support a new drug application. Finally, let me remind you that there is nothing approved for the treatment of Rett syndrome. Rett is a devastating and burdensome disease for both the patients and their caregivers, often requiring around-the-clock support. We have had several discussions with key opinion leaders and experts in the field. They informed us that even a modest improvement in symptoms could make a significant and very meaningful difference in the ability to care for patients and their overall functioning. We look forward to announcing the results of this study in the near future. Slide 15 shows a summary of our Phase 3 program evaluating Pimavanserin for the treatment of the negative symptoms of schizophrenia, which includes two pivotal studies: our positive ADVANCE 1 study and ADVANCE 2, which we initiated in the third quarter of last year. Please turn to Slide 16 for an update on our ACP-044 program. Our ongoing Phase 2 study evaluating ACP-044 for the treatment of postoperative pain following surgery is nearing enrollment completion. However, we now expect the results in the first quarter of 2022. This slight delay is due to slower than expected enrollment with the postponement of many elective surgeries during the summer of the COVID-19 Delta variant surge. Additionally, as a reminder, earlier this year, we initiated a Phase 2 study for patients suffering from pain associated with osteoarthritis and plan to provide an update on this study next year. Slide 17 highlights a brief summary of our ACP-319 M1 pen program for the potential treatment of schizophrenia and cognitive impairment in Alzheimer's disease. We recently initiated a multiple ascending dose study as our Phase I work continues for this program. Turning to Slide 18, at ACADIA, we're committed to investing in therapies to address high unmet needs in CNS. Our clinical development pipeline has two late-stage Phase III programs, as well as multiple early-stage programs. This year, we have initiated multiple clinical studies, including ACP-044 in acute pain in Q1, ACP-044 in chronic pain in Q2, and most recently, the ACP-319 multiple ascending dose study. With that, I'll turn the call over to Mark.
Mark Schneyer, CFO
Thank you, Serge. Today I will discuss our third quarter 2021 results. Please turn to Slide 20. In the third quarter of 2021, we recorded $131.6 million in net sales, an increase of approximately 9% compared to $120.6 million of net sales in Q3 of 2020. Our net sales increase in Q3 2021 represents a 3% volume growth year-over-year. The gross to net adjustment for Q3 2021 was 15.2%. Weeks of inventory in the channel at the end of the third quarter were slightly down. As a result, sequential demand growth of approximately 3% was slightly higher than sequential selling growth of approximately 1%. Moving down the P&L, GAAP R&D expenses decreased to $58.6 million in the quarter compared to $120.1 million in Q3 2020. Recall last year, GAAP R&D expense included the $52.8 million upfront consideration transaction costs related to our acquisition of suicide therapeutics. GAAP SD&A expenses were relatively flat at $81.7 million in the third quarter compared to $81.6 million in the third quarter of last year. Non-cash stock-based compensation expense during the quarter was $15.5 million compared to $21.4 million for the same period in 2020. Our cash balance at the end of the quarter was $540.3 million. I'll now provide some additional color on our financial expectations and guidance ranges for the remainder of the year. Please turn to slide 21. As we mentioned previously, our commercial team is continuing to execute well and deliver quarter-over-quarter growth with strong relative performance in both channels. As a reminder, in the fourth quarter we expect a much higher impact from gross to net as a result of accruing for the donut hole obligation associated with year-end inventory in the channel. In addition, recall that last quarter we guided to gross net being somewhere around 20% for the full year. As we get closer to the end of the year, we have narrowed the top end of our full-year 2021 net sales guidance range to $480 million to $500 million from the previous range of $480 million to $515 million. Our net sales guidance assumes that inventory levels remain relatively flat in the channel as we approach the end of the year. I'd like to provide a little bit more commentary on our net sales guidance. As we saw in Slide 8 of Brendan's presentation, our leading indicators of PD office visits and LTC occupancy rates have started to improve in the first half of the year. However, in the third quarter, they seem to have leveled off or declined. This is a reflection of the COVID-19 Delta variant surge we experienced in the summer. Our net sales guidance range factors in scenarios on how long our leading indicators remained relatively flat versus how quickly they returned to growth. Moving onto the expense side for 2021, we have lowered our GAAP R&D guidance to be between $230 million and $245 million for the full year from our previous range of $250 million to $270 million. Lastly, we have slightly narrowed the top end of our GAAP SD&A full-year guidance range to be between $385 million to $405 million from $385 million to $415 million. And with that, I will turn the call back over to Steve.
Stephen Davis, CEO
Thank you, Mark. Please turn to Slide 23. In closing, I would like to remark on how proud I am of our teams for their execution this year. Our commercial team has worked tirelessly all year on delivering Pimavanserin to more Parkinson's patients and their families who are suffering from the symptoms of psychosis. They've achieved more with less and continue to push through the pandemic conditions. Our R&D team has executed during a time when patient enrollment is difficult. We're now poised to report out on two key clinical studies. These include the results from LAVENDER, our Trofinetide study in Rett syndrome, and Phase 2 results from our ACP-044 study in postoperative pain. Of course, we look forward to providing additional clarity regarding ADP around year-end. Finally, I would like to thank all of our employees for their commitment to our mission to elevate lives. I will now open up the call for questions.
Operator, Operator
Please stand by while we compile the Q&A roster. Our first question comes from the line of Neena Bitritto-Garg from Citi. Your line is now open.
Neena Bitritto-Garg, Analyst
Thank you for taking my question and congratulations on the quarter. I have a question regarding the commercial performance of NUPLAZID. Can you provide any insights on the pace of new starts during the quarter compared to Q2? Additionally, based on some of Mark's comments, it seems we should anticipate a higher gross to net and similar patient trends from one quarter to the next. Should we assume that Q4 might actually be a down quarter? Thank you.
Stephen Davis, CEO
Yeah, thanks for the question, Neena. I'm going to ask Brendan to answer the first question, Mark, the second.
Brendan Teehan, CFO
Neena, thanks for the question. The question regarding new patient starts in the third quarter, we are seeing new patient starts that are approaching the pre-pandemic levels. So largely comparable between the quarters. As we head into the fourth quarter with DTC and our increased efforts with our HCP campaign, we would expect to continue growth moving into 2022.
Mark Johnson, Vice President of Investor Relations
Thank you for the question. I want to highlight that there is volume growth across the entire guidance range for net sales. However, we do anticipate a higher gross net adjustment for the fourth quarter at the lower end of that range. Consequently, this means that reported net sales at the bottom end of the range would be lower than the reported net sales in the third quarter.
Neena Bitritto-Garg, Analyst
Got it. Thanks, guys. I appreciate it.
Gavin Scott, Analyst
I'm Gavin standing in for Cory. We had a question regarding the regulatory aspects of the drug candidate for DRP, as it was initially expected to be invested in. However, there are now plans to initiate a Phase 3 trial next year for ADP specifically. Have you received any feedback from the agency about their broader thoughts on the DRP setting in relation to the independent components, as this development seems to strengthen your position?
Stephen Davis, CEO
Again, and I didn't hear the second part of that question. Could you repeat that part?
Gavin Scott, Analyst
I just said that this development would seem to help your case.
Stephen Davis, CEO
Got it. Okay, thanks. Well, we can't obviously comment on what other people's interactions are with the FDA. I'll just simply say that they have made it clear to us that they think the correct way to assess this population based upon reviewing our data is on a subgroup by subgroup basis. So that's what we're focused on. That's what we'll be focused on in the next week.
Ritu Baral, Analyst
Hi everyone. Thank you for the question. I wanted to follow up on the previous inquiry. I was considering asking it from a slightly different angle. As you prepare for this meeting and look ahead, if the FDA remains firm, is an ADP-specific trial the best course of action given that you have clearly demonstrated treatment effect? It would require a well-designed study to cover 60% to 80% of the overall DRP population. Additionally, as you plan to discuss 019, could you remind us if the FDA changed their view on whether they regarded 019 as a well-controlled study? I believe this was related to the administrative single-center aspect. Can you clarify their interpretation of well-controlled versus ACADIA's execution of the study? Thank you.
Stephen Davis, CEO
Thank you for the question. I'll address the first part, and then Serge can respond to the 019 portion. To summarize, we received a Complete Response Letter in April. During our Type A meeting, the FDA clarified that they are evaluating dementia-related psychosis on a subgroup basis. In that meeting, we presented data to show consistency in response between drug-treated patients and those on a placebo. We conducted a cluster analysis that broke down individual components of the scale used during the study in Houston, both for enrollment and during the 12-week response period, as well as during the 6-month randomized phase. The results indicated a consistent response across all subgroups. Patients exhibited similar responses when entering the study and continued to respond comparably during the randomized phase. However, in the placebo group, we observed a quicker relapse among patients with both Parkinson's disease and dementia compared to placebo patients in other subgroups. We believe this is due to the dopaminergic therapies used by these patients, which may worsen psychotic symptoms. At the end of that meeting, the FDA acknowledged our points and emphasized that the most effective approach to study this population is on a subgroup basis, suggesting we conduct an additional study for each of the subgroups for which we are seeking approval. Although we had a limited time for discussion in that meeting, they expressed willingness to reconvene if we wished to further talk about the possibility of resubmitting without another clinical study. Currently, we believe the subgroup with the most potential is Alzheimer's disease psychosis, which comprises around 70% of the population in our HARMONY study and similarly represents about 70% of dementia patients epidemiologically. Our study 019 also yielded positive results in the Alzheimer's dementia psychosis population. For all these reasons, we are focused on our next meeting and the new analyses we've conducted since our last discussion, specifically regarding the Alzheimer's disease psychosis population. We look forward to that meeting, as it is essential for determining our next steps. Serge, would you like to address the 019 study?
Serge Stankovic, President
Yes, thank you. In respect to the 019 study, just a reminder on the Alzheimer's disease psychosis study that was conducted in a number of care homes in the UK. The FDA raised certain issues that in the complete response letter expressed concern that makes it difficult for them to consider this study adequate and well-controlled. These issues by the FDA can be roughly categorized into two buckets: one is related to the design of the study and the others are related to conduct of the study or the protocol deviations that were recorded and reported in the study. In respect to design, two specific issues were emphasized: one, that this is a single-center study, and the second is that there was no type 1 error control for the secondary outcomes. We believe that we can and we intend to address these concerns, particularly from the perspective that in our understanding none of these are requirements for an adequate and well-controlled study. Just a reminder, as I said, this study was done under the coordination of a single investigator in the UK. But it was done in a number of care homes or nursing homes throughout the broader UK, London area. From the perspective of the conduct, we also intend to address, not only in detail, specifically the protocol deviations that are reported. By the way, they are reported in the study report from the very beginning, and we discussed that, that we will further elaborate on specifics and timing and their ability to impact the study per se, and the interpretation of the results. So in short, we are from the data perspective, we have a level of comfort that we can address these concerns raised by the FDA. That is exactly what we intend to do in our meeting, as well as eventually in the re-submission. We believe that following that, this study can and should be considered an adequate and well-controlled study and supportive in the overall as independent evidence of efficacy of Pimavanserin in Alzheimer's disease psychosis.
Ritu Baral, Analyst
Got it. Thanks.
Charles Duncan, Analyst
Hi. Good afternoon, Steve and team. First of all, thanks for taking our question and congrats on a solid quarter. I wanted to ask you one commercial question and then one pipeline question. Regarding the commercial question, I guess I'm thinking about the two new campaigns for HCPs and direct-to-consumer. And I think Brendan suggested that a higher percentage of PDP diagnosis would be the goal. I guess I'm wondering if you could provide us some color on where you're at today and where you'd like to be in say, 12 months?
Stephen Davis, CEO
Sure. Brendan, go ahead.
Brendan Teehan, CFO
Excuse me, Charles. Thank you very much for the question. First, I'd say we're excited about both campaigns. The HCP campaign is focused on drawing attention to the ability to improve psychosis while not impacting motor function. We know that our patients are going to see their HCPs principally because of their Parkinson's disease. And we need to weave in the story about Parkinson's disease psychosis and the need to treat. We've done market research on the campaign. HCPs are responding very favorably to it. They demonstrate a higher interest in prescribing NUPLAZID as a function of telling the story that way. The second campaign is more focused on patients and caregivers. You can see in the DTC story, which is to first of all, highlight NUPLAZID as the solution to Parkinson's disease psychosis. But just as importantly, to make sure that those patients and caregivers understand that this is a normal part of their Parkinson's disease experience, and thus it's important to bring that situation to their HCP's attention. So we are using those in a complementary fashion. We've been very proud of the DTC campaigns up to now and how that has engaged patients and caregivers with their treaters in that conversation, and we're very confident that that will happen again here.
Charles Duncan, Analyst
Okay. And then, the second question is for Serge on the pipeline. Perhaps you just answered this in addressing Ritu's question, but I'm wondering if you could provide us a little bit more color on the new analyses that have been conducted. Are they primarily around efficacy? Are they around safety? I mean, Brendan just mentioned a lack of impact on motor function, and it would seem to me that would be important as well as cognition in the ADP population. So what kind of analyses have you conducted, and then secondarily, when would you be able to update this? Would the meeting happen by the end of the year, or would you be in a position to update by the end of this year or so?
Serge Stankovic, President
Yes. Thanks, Charles. Let me just get one-by-one. In regard to new analysis, I'll start first of all by stating something that we previously also stated, that questions raised in the complete response letter were related to the way or how the efficacy evidence in the patient population should be derived, and that the, as Steve says, what is the appropriate way of evaluating efficacy in dementia patients with psychosis, whether as a group or by dementia subtype. So as you can imagine, most of the discussions that we have is around that evidence efficacy in the patient population. In this specific case, we're preparing a number of analyses that are specifically designed to where is a naturally to start with a subgroup, and that is the largest subgroup of Alzheimer's disease psychosis, where we are providing a broader additional analysis. I'll comment on that just in a second, but also, I don't want to address your question about safety. Because the Pimavanserin safety profile is unchanged, and all the additional data that we have provided in the supplemental NDA did not open any new questions in regard to the safety of Pimavanserin, that calls as well for the certain safety benefit that we say with Pimavanserin, and that is related to the motor function. Specifically in this patient population with dementia, we observed a lack of negative impact on cognition and cognitive functioning. Of course, that is part of our supplemental NDA submission. It's also part of this discussion where we are certainly providing the information in that respect. In regard to specifically Alzheimer's disease psychosis and the additional evidence, that can be grouped into three different groups. One is related to the primary and secondary outcome, and that is of the reduction in relapse as well as reduction in the upper clause of discontinuation in this specific group where we are providing a variety of ways of looking into that analysis and demonstrating the benefit that is clinically meaningful and substantive. As I mentioned in the prepared remarks, between 40% and 50% reduction, where we are also providing not only the overall in the Alzheimer group but also specifically in the larger group of patients that received 34 milligrams, which is the recommended dose in PDP and recommended dose in DRP or Alzheimer disease psychosis. The second group of analysis is following the severity, different ways of measuring severity of psychotic symptoms in all of the patients following randomization, either to continue active treatment with Pimavanserin or to discontinue Pimavanserin and switch to placebo also placebo. We are following over time the severity of symptoms in these two groups of patients, both on the scale for psychotic symptoms with hallucinations and delusions as well as in the clinical prep +of change and improvement where we are looking and demonstrating that patients that remained on treatment continue overall, continue with the benefit of Pimavanserin in terms of control of psychotic symptoms. We're also looking on the relationship of dose and drug exposure, pharmacokinetic exposure, and the efficacy of the drug is another way of looking at the effects that we're seeing and the benefit that we're seeing in that are receiving Pimavanserin is real through FX and not finding. The third group of evidence is really related to the broader overview of the response across different dementia subtypes and characterization of psychotic symptoms prior to treatment following the treatment with one purpose: demonstrating that the benefits that we're seeing across this subgroup is not a supportive evidence that what we are seeing in Alzheimer's disease psychosis is subgroup is a real effect. Finally, I will just mention that we are also looking at a categorical presentation of response across different categories of patients, specifically in the Alzheimer disease psychosis, and confirming again both overall and in the 34 milligram group the substantive evidence of benefit in treating patients with Pimavanserin. So I hope this helps on a broader scale.
Charles Duncan, Analyst
Definitely. Look forward to hearing the response from the agency. Hopefully, they allocate more than an hour to you and forget about the timing of the response will just hear when we hear it.
Serge Stankovic, President
I apologize for that. I'll address it now. It just slipped my mind. We are on track with the schedule for the meeting and expect to receive the minutes from it around the end of the year, but given the year-end holidays, it's a bit challenging to confirm whether we'll get the minutes before the year ends or shortly after the NDA. So, we are estimating the timing to be around the end of the year.
Yatin Suneja, Analyst
Thank you for taking my questions. I have a few inquiries regarding Trofinetide. You're focusing on two co-primary endpoints. Can you share what agreement you have with the FDA if you achieve one, and what you're aiming to demonstrate with both the RSBQ and CGII? Additionally, could you confirm whether all patients have entered the open-label portion of the study, or if there are any patients who chose not to participate after the 12-week treatment period?
Stephen Davis, CEO
Yes, thanks so much for the question. Serge, you want to take over those?
Serge Stankovic, President
Yes, I'm happy to. Thanks, Jeff. I want to mention that we are facing some challenges, but it's just a slight delay. We expect to complete the enrollment before the end of the year, and therefore, we should have top-line results sometime within the first quarter or toward the end of it. This expectation comes with some uncertainty, especially considering the nature of elective surgeries and enrollment. Nonetheless, that is generally our outlook.
Jeff Hung, Analyst
Thank you.
Marc Goodman, Analyst
Serge, you explained nicely what new data you are going to be giving to the FDA when you do the meeting. But I'm just curious, there were a couple of slides that you went over with us today. Has the FDA even seen that data, that subgroup data on Alzheimer's?
Serge Stankovic, President
Yes, Marc. Thank you for the question. We discussed some of this in the previous meeting. They have seen some of the beta discussion regarding what we should provide. However, there are still some outflows in this analysis that haven't been covered. It's a bit of a mix in that aspect, but we have given them a good general idea of the direction we're heading. We will offer much more detail in the next meeting regarding the outflows and specific data.
Marc Goodman, Analyst
Okay. And then just separately, commercial question, can you just give us a sense of how the reps in the office has just changed relative to the second quarter, and how in the third quarter and then how fourth-quarter has changed? Just give us a sense of the past four months how that's changed.
Stephen Davis, CEO
I think good question, Marc. Brendan, you want to take that?
Brendan Teehan, CFO
Sure. Marc, thanks for the question. We have seen improved access rates for our representatives, both in the community and LTC setting. I think we've previously reported very much in line with what we've seen in the industry. We're up around 70% of visits being face-to-face. It varies a little bit between community and LTC. But we're encouraged by what we're seeing so far in the early fourth quarter.
Marc Goodman, Analyst
And where were we three months ago?
Brendan Teehan, CFO
So we were reporting in the 60% to 65% range. So it's continuing to mark up.
Stephen Davis, CEO
A little bit more, it's very low at the beginning of the year for us and everyone else. And what we've seen in the industry is month-by-month from the beginning of this year, those numbers were really going up on a very continual and meaningful basis. With the Delta variant, you saw that slow down quite a bit. So what we're seeing today is, as Brandon mentioned, about 70% of our details are in-person, about 40% for virtual. As we see the impact of the Delta variant pull all the way through, and you guys are all seeing the same price that we are, I think we're probably approaching that point now; we'll see the impact of the Delta variant pass as well.
Gregory Renza, Analyst
Good afternoon, Steve and team. Congratulations on the quarter and thank you for taking my question. Steve, I wanted to follow up on the regulatory update regarding your engagement with the FDA. In the past year, you've described the relationship as more of an agreed to disagree position concerning the overall DRP versus the subgroups. I'm curious if you can briefly comment on how that has evolved. Has there been any change as you prepare for the subgroup meeting, particularly in relation to starting with all Alzheimer's disease? I would also like to know your level of enthusiasm about this approach for the European indication moving forward. Thank you very much.
Stephen Davis, CEO
Thank you for the question, Rick. I'll provide some context. Currently, there are no approved medications for treating dementia-related psychosis or Alzheimer's disease psychosis, which puts us in a pioneering position. We have amassed what is likely the largest safety database for patients with these conditions and made significant progress in understanding how to treat them. Our stance remains that the optimal method for studying this group is to consider dementia psychosis collectively. This approach is supported by previous discussions about the similarities in symptoms and responses. However, recognizing the lack of data in this emerging field, we understand that opinions may vary, and the FDA has a different perspective, advocating for examination on a subgroup basis. We have adapted our focus accordingly in anticipation of the upcoming meeting. As I mentioned, the FDA has involved their psychiatry division and has been actively engaged, highlighting the importance of this issue to both parties. We aim to reach a conclusion in this next meeting and are eager to progress. If the FDA maintains their current level of engagement, we are optimistic about the outcomes. Nonetheless, we acknowledge that this is a new and uncharted area. Looking at our data on Alzheimer's Disease psychosis, we believe it strongly supports the effectiveness and safety of Pimavanserin for this patient group. We need to meet with the FDA to seek a consensus on this.
Gregory Renza, Analyst
Thanks, Steve. I appreciate the call.
Ami Fadia, Analyst
Thanks for taking my question. I had a follow-up on DRP. And one of the question is slightly different way. Is the point of contention with the FDA whether there is adequate data in the Alzheimer's disease populations, or whether or not the Phase II study can be viewed as acceptable as part of the registration package? If you could give us your best view on that. And then I'll have a different question.
Stephen Davis, CEO
Well, I'll try to give you a little bit of additional color. And then Serge, feel free to jump in with anything else you might want to add. I think when we designed our Phase III program, and we aligned with the FDA about how to pursue that program, we and the FDA aligned around a design that was not to study Alzheimer's disease psychosis or to mention with Lewy Body psychosis or Parkinson's dementia psychosis. It was to study all of the subgroups as one single group, so that's the Phase III program we ran. Today, as just described, the FDA has a perspective that we should be looking at things, or they are looking at things on a subgroup-by-subgroup basis. From that perspective, we're in a situation that is a little atypical because we're talking about now a group that was not where we did not design the study to show statistically significant data on a subgroup basis. But we have very clinically meaningful results in that subgroup. As Serge described, I think very thoroughly we have looked at things from a multitude of cross-sectional perspectives to see if we have consistency in there, and we do. We also have our 019 study that was focused on just Alzheimer's disease, psychosis patients. But we have a positive study there. For all those reasons, as we said, we're very focused now on this next meeting and taking new analysis that we've done since the last meeting that focuses on the Alzheimer's disease psychosis population. So we look forward to having that meeting; obviously, that's the next step we need to have the meeting, and as soon as we have, we'll be able to give further guidance about next steps.
Ami Fadia, Analyst
Great. That was very helpful. My second question is on Trofinetide, and you answered the question earlier about the co-primary endpoints and the clinical meaningfulness of those. I understand that any type of improvement would be welcome in this patient population. However, as we think about the chronic nature of treatment and the possible requirements of other supportive care for these patients, how would you think about pricing the drug should it get approved?
Stephen Davis, CEO
Thank you for the question. While I would like to provide an answer, it's a bit early for us to discuss pricing at this stage. The next step in that program is to review the results and, if we have findings that support an application, we will proceed with filing. I want to emphasize that, similar to our approach with NUPLAZID, we intend to set the drug's price based on the value we provide. In the wider population, the situation is quite unfortunate due to the significant disease burden. If we can enhance the lives of those patients and their caregivers, we believe that will be crucial from a medical standpoint.
Paul Matthias, Analyst
Thanks so much. I had a couple of questions on the re-powering strategy and just the DRP data in general. I guess one is just kind of related to reconciling one thing we've had trouble wrapping our heads around, and that is, you speak to patients with DRP presenting similarly and responding similarly. But just going back to the forest plot, the hazard ratio in Parkinson's is around 0.1, and it's a lot higher in other subgroups, except for Lewy Body. So I was just kind of curious how you explain that in the sense that is it not driven by biological differences in disease in your view? And then second on the ADP subgroup, can you just speak to statistics or anything around that that can kind of quantitatively bolster your case? I know you talked about a 40% relapse reduction, but the hazard ratio upper bound is almost 1.5. How do you think FDA will view that quantitatively speaking or if there's any sort of p-value that's tied to it? Thanks so much.
Stephen Davis, CEO
Thanks for the question, Serge, you want to take those?
Serge Stankovic, President
Yes, let me address the first question. Paul, you mentioned the main question regarding the observed hazard ratio in Parkinson's disease psychosis compared to other dementia subgroups like Alzheimer's. I believe the question is whether this indicates a biological difference in response or if there's another factor at play. First, when we examine the relapse rates in patients on Pimavanserin versus those on placebo after randomization, we see that relapse rates among dementia subtypes are quite similar for the Pimavanserin groups. The significant difference arises in the placebo group, where patients who discontinued treatment relapsed much faster, particularly in Parkinson's disease patients. We discussed why this is occurring: while on active treatment, relapse rates remain similar across subtypes. We believe this is due to patients on dopaminergic therapies for their motor functions having additional complicating factors that can worsen their psychotic symptoms upon stopping antipsychotic treatment. We are planning to present further data to the FDA on this, recognizing that the samples are small, particularly for patients not in the Parkinson's group. However, we can analyze this to see patterns. Our data suggests that the observed differences are not due to biological factors but rather confounding effects related to concomitant therapies in this subgroup. I hope this clarifies the variance in the hazard ratios. As for the second part of your question, I need a reminder, as I lost my train of thought while discussing this.
Paul Matthias, Analyst
Yeah. No worries Serge, and thank you for the thoughts; that was super interesting. As it relates to the ADP subgroup, right? I mean, we see the 40% relapse reduction, but we also see the hazard ratio for the 95% confidence interval. The upper bounds are almost 1.5, which would suggest this is really far away from statistical significance or at least there's a ton of, I guess, just sample size issue in the data; and I'd be curious how you think about that.
Serge Stankovic, President
As Steve said, the study is not designed to test statistical separation in the subgroups because we needed more patients in each of the subgroups in order to see that as reasonable power. So confidence intervals that you are seeing are actually simply a consequence of the sample size that we have. The smaller the sample size, the larger the confidence intervals that you're talking about. But what we are presenting is a body of evidence related to Alzheimer's disease psychosis, a number of different analyses. Some of them reached nominal statistical significance, some do not. What is the important point is consistency of that effect. The question is, is the 40% or 50% risk reduction we're seeing? Nobody argued that it's clinically meaningful and robust. The question is, is that a spurious finding or is it a real true effect. One way to demonstrate that is to look to the consistency of different analytical approaches, different outcome measures, different time points, and point out that consistency. I'll say sometimes it is not significant; sometimes it is significant nominally because some of these analyses are not controlled for Type 1. But the point is, if you see something consistently, you start to be convinced that it is actually a true effect and true benefit rather than some spurious chance finding.
Paul Matthias, Analyst
All right, thank you so much, sir.
Serge Stankovic, President
Thank you.
Operator, Operator
At this time, I'm showing no further questions. I would like to turn the call back over to Steve Davis for closing remarks.
Stephen Davis, CEO
Great. Thanks much, Operator. Thanks again, everyone for joining us today. We look forward to updating you on our progress next quarter.
Operator, Operator
This concludes today's conference call. Thank you for participating. You may now disconnect.