Alkermes plc (ALKS) Q3 2017 Earnings Report, Transcript and Summary

Good morning, and welcome to the Alkermes Plc’s Third Quarter Financial Results Conference. My name is Brendon and I’ll be your operator for today. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session [Operator Instructions] Please note this conference is being recorded. And I will now turn it over to Sandra Coombs, Co-Head of Investor Relations. Sandra, you may begin.

Thank you. Welcome to the Alkermes Plc conference call to discuss our financial results for the quarter ended December 30, 2017. With me today are Richard Pops, our CEO; Craig Hopkinson, our Chief Medical Officer; and Jim Frates, our CFO. Before we begin, I encourage everyone to go the Investors section of alkermes.com to find our press release and related financial tables, including a reconciliation of the GAAP to non-GAAP financial measures that we’ll discuss today. We believe the non-GAAP financial results in conjunction with the GAAP results are useful in understanding the ongoing economics of our business. Our discussions during this conference call will include forward-looking statements. Actual results could differ materially from these forward-looking statements. Please see our Slide 2 of the accompanying presentation, our two most recent 10-Qs and also our 10-Ks for the year ended December 31, 2016, for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided on this call as a result of new information or future results or developments. Today, Jim will discuss our financial results and Richard will provide a prespective on recent news items. We also have a number of pipeline updates to share with you today, soon to departure from our regular earnings call format. Dr. Craig Hopkinson, our Chief Medical Officer, will provide an overview of our development pipeline as well. After our remarks, we will open the call for Q&A. Now, I’ll turn the call over to Jim.

Thanks, Sandy. Good morning, everyone. Our third quarter results reflects solid top-line performance driven by a proprietary commercial products and our royalty and manufacturing business as well as disciplined expense management. With only one quarter of 2017 remaining, today we are revising our financial expectations to reflect our results year-to-date and our expectations heading into the last two months of the year. I’ll start with the financial highlights for the quarter. During the third quarter, total revenues grew 21%, to $217.4 million, compared to the third quarter of 2016, driven by solid year-over-year growth of our proprietary commercial products and continued strength from our royalty and manufacturing business. These revenue results driven by slightly lower than expected VIVITROL® growth, were offset by expense management during the quarter, which allowed us to advance our development pipeline, while generating solid bottom line performance. For the third quarter we reported a GAAP net loss of $36.3 million, and a non-GAAP net income of $4.2 million. Starting with VIVITROL®, in the quarter net sales were $69.2 million, reflecting 24% growth compared to the same period last year, with 5% growth sequentially. These results were lighter than our expectations. We believe this was primarily the result of three factors: the draw down in the inventory in the channel, lower than expected growth in some of our larger states which disproportionally effects overall growth. And delays in federal funding, related to 21st Century Cures, flowing into the treatment system. Our third quarter results underscore the VIVITROL as a unique product in an unusual market. Looking forward, we continue to monitor new state progress as a leading indicator for interest in VIVITROL and that growth remains strong. During the third quarter, we saw the number of programs expand from approximately 500 to more than 560 programs. Based on our results year-to-date, we are revising our 2017 expectations for VIVITROL, down to a range of $265 million to $275 million, which reflects approximately 30% growth, compared to 2016. Turning to ARISTADA, third quarter net sales of $24.5 million where within our expectations and represent 8% sequential growth, compared to the second quarter. During the quarter we continue to gain traction in the growing market for long-acting atypical antipsychotics. ARISTADA’s market share for new prescriptions in terms of months of therapy in the long-acting aripiprazole market, was approximately 24% in the quarter, compared to approximately 15% in the third quarter of last year. Based on these results we expect fourth quarter net sales of ARISTADA to be in the range of $27 million to $30 million, in line with our expectations for ARISTADA net sales to approximately double for 2017. With the launch of the two-month dose last quarter, and the new progress being made on the ARISTADA product family, we’re well-positioned to keep growing this important medicine. Moving on to our partnered products we saw overall revenues of $122.7 million in the third quarter, compared to a $110.3 million in the third quarter of last year. Of note, this included strong manufacturing royalty revenue of $79.4 million related to a RISPERDAL CONSTA and INVEGA SUSTENNA and INVEGA TRINZA, which increased from $73.3 million for the same period last year. In terms of expenses, our total operating expenses for the third quarter of 2017 were $255.7 million, compared to $241.4 million for the same period last year. This year-over-year increase was driven primarily by investment in the company's development pipeline and commercial organization. R&D expense during the third quarter was somewhat lighter than expected, primarily due to timing. Therefore we're lowering our expectations for R&D to a range of $400 million to $420 million for 2017. We're also able to decrease our expectation for SG&A expense to a range of $410 million to $430 million for 2017, driven by disciplined expense management and the timing of certain commercial initiatives. Overall, we're maintaining our non-GAAP expectations for the year, which continue to be in the range of a non-GAAP net loss of $15 million to a non-GAAP net income of $15 million, as our lower spend offsets the decrease in our expectation for the top line. Turning to our balance sheet, we're in a strong position in the end of the third quarter of 2017, with approximately $569 million in cash and total investments. We continue to focus on executing on our business strategy, to grow our commercial product and invest in the late-stage development programs that we expect will be our future growth drivers. Our growth expectations for both VIVITROL and ARISTADA remain high and you'll hear more from Rich on these plans. We look forward to a solid fourth quarter as we continue to drive our growth. With that, I'll turn the call over to Richard.

That’s great. Thank you, Jim. Good morning, everyone. We have a lot going on at the company. New drug applications for ALKS 5461 and ARISTADA, new data being generated and presented for ALKS 3831, VIVITROL and ARISTADA, and critical milestones approaching for almost every program as we end the year and head into 2018. There are a number of updates we want you to be aware of today. So we decided in legal scheduling a separate webcast to expand this call to include more extensive R&D update. This also gives me a chance to introduce Dr. Craig Hopkinson, our Chief Medical Officer, who recently joined us from Vertex. Craig joins the R&D organization led by Elliot Ehrich, most of you know, we’ve already having an impact here. So what we will do, I’ll share my perspective on some of the important developments on VIVITROL and ARISTADA, in particular and then ask Craig to update on another programs, including a first look at our 4230 immunooncology program. I want to start with VIVITROL. Jim take you through some of the background to the numbers, but from my perspective, the sequential growth during the quarter is more indicative of the unique nature of this market than the long-term potential of the medicine. We are in the midst of the national crisis. VIVITROL is an increasingly important element in addressing it. And it’s growing and I believe this growth is going to continue. I believe it so strongly because we’re also at the beginning of a paradigm shift in the treatment of opioid dependence in the country. There is a confluence of new data, policy and funding being integrated into a national response to this epidemic. The status quo isn’t adequate and will change by necessity. First, we'll talk about the data. Just last week, JAMA Psychiatry published important positive results from a first of its kind study directly comparing VIVITROL to buprenorphine naloxone or SUBOXONE, which is the most widely used treatment for opioid dependent. VIVITROL performed as we would have expected. The study demonstrated that VIVITROL was as effective as SUBOXONE on retention and treatment and reducing use of heroin and other illustrated opioids. Importantly, VIVITROL patients also demonstrated significant reduction in opioid craving and reported high treatment satisfaction throughout the 12-week study. These comparative data build up on the existing substantial body of evidence, supporting these VIVITROL and the value of Medication-Assisted Treatment, called MAT in general. And there will be more data later this year, we expect the results of nine of the X-spot study, which also seeks to directly compare VIVITROL to buprenorphine. Each of these studies has its limitations, but in the aggregate, more data supporting the use of MAT will drive change. MAT is grossly underutilized. We’re encouraged that the research community is actively generating new data about the utility of VIVITROL and other MAT for this underserved patient population. The next element is policy. The goal is to evolve the treatment paradigm to a patient-centered approach to ensure that all patients were informed to have access to all available treatment options. This requires action on the part of federal and state policy makers, as well as other participants in the system. Alkermes is an active player on this front. Last month we provided testimony in separate meetings to the Department of Health and Human Services and to the President’s commission on comparing drug addiction and the opioid epidemic. We outlined the role of VIVITROL in the treatment landscape and its features as a non-narcotic, long-acting treatment option that is not diverted or sold illicitly. We also testified about the importance of equal access to all FDA-approved medications for opioid dependents and recommended to a commission that they focus on the implementation of the Comprehensive Addiction and Recovery Act that was passed into law last year. We look forward to Commission’s final recommendations in its report to the President, which is expected just in the coming days and for plans to implement the recommendations coming out of the White House in the weeks ahead. I also want to note FDA commissioner Scott needs testimony yesterday in front of the House Energy and Commerce Committee. He said and I quote, “FDA will take steps to promote more widespread use of existing, safe and effective, FDA approved therapies to help combat addiction. There are several FDA approved treatments. All of these treatments work in combination with counseling and psychosocial support. Everyone who seeks treatment deserves the opportunity to be offered all three options as a way to allow patients and providers to select the treatment best suited to the needs of each individual patient.” This has been our message for the past several years. It’s beginning to be heard and to be translating into policy. On the funding front, new funds are being deployed. Last year 21st Century Cures Act provide $1 billion of new funds to address the opioid epidemic. That money has been slowed to move from federal to state government and into the community, but it will as a matter of law and as matter of necessity. State houses around the country, appropriators are allocating new funds to combat the crisis in their communities. Later today, the President will make an announcement regarding in the actions administration will take to address the opioid crisis. Setting the stage for the commission's report and underscoring the central focus at epidemic taking in our national dialog. So in summary, with new data being generated and presented to the treatment community, policy makers focus on solutions and new funding flowing as a treatment, we have the opportunity to change how the country is addressing this public health crisis. VIVITROL and Alkermes are key elements of this discussion and we will continue to be on the frontlines advocating for patients. Next is ARISTADA. With important new developments to report. Patient-centered solutions have been at the core of our ARISTADA development program since the beginning working on the program eight years ago. You can see the products stand we blossomed year-by-year and we’ve asked you to watch what we do and I think now it’s becoming more clear. This morning we made two announcements to revel how fast the product family is evolving. First, we revealed that we submitted the new drug application for our new aripiprazole lauroxil formulation, design to enable simple initiation on to ARISTADA. We kept this development program under wraps for competitive reasons. As this initiation product has critical new dimension of flexibility to the product family and enables initiation without the need for three weeks of oral supplementation. This new initiation product is a single injection, designed to make studying ARISTADA even easier for both patients and their healthcare providers. Based on our NanoCrystal delivery system, which enables a faster release profile than the formulation employed in our monthly six-week and two-month dosage forms. And it’s well-suited for initiation of treatment for patients not currently taking oral aripiprazole. The second announcement builds on the first and relates to the upcoming initiation of an ambitious new Phase 3b study, comparing ARISTADA to the current market leader in INVEGA SUSTENNA. These two products offer the greatest flexibility in terms of doses and durations. We want to continue to build the evidence based support in expanded use of ARISTADA. The study will employ two key features of ARISTADA. Our new initiation regimen I just described, along with the two-month ARISTADA dose. Simple initiation and two months of therapeutic coverage may have important, real world utility and particularly useful for patients transition from inpatient care to more complex outpatient settings. When patients with schizophrenia are particularly vulnerable to relapse. This study builds upon positive Phase 4 data we presented in September. This demonstrated the switching patients would experience inadequate response are intolerance to INVEGA SUSTENNA. Two treatment with ARISTADA that just statistically significant and clinically meaningful improvement in schizophrenia symptoms. Taking together, these studies will continue to build the story of ARISTADA’s positioning alongside the class leader. Our vision for ARISTADA is a bold one, to become the gold standard of treatment among the long-acting injectable antipsychotics. So that’s all I'm going to cover. Now I want to introduce Craig Hopkinson, our new Chief Medical Officer and Senior Vice President of Clinical Development and Medical Affairs. Among other things, Craig is enhancing our Medical Affairs function as we prepare for the anticipated launch of ALKS 5461, where we will be educating the treatment community on this new mechanism of action for the treatment of depression. Craig is also responsible for the advancement and implementation of our clinical pipeline development programs. With that, I'll hand the call over to Craig.

Thank you, Richard. I'm excited to be joining Alkermes at such an important time for the company's top line of development candidates. I'm pleased to be able to share with you today important updates across our top line portfolio. I'll start with ALKS 5461, our Fast Track designated medicine in development for the threshold. First, this is an important medicine and one of the key reasons I joined Alkermes. When introducing a new mechanism of action into an established treatment paradigm, educating physicians and engaging key business is critical to launch and to long-term success. This is typically true in a disease space of depression, where there hasn’t been a novel mechanism of action in 30 years. We know that healthcare providers are eager for safe and affected new treatments options for the millions of patients that do not get adequate relief from standard anti-depression therapy. I found the foundational understanding of the endogenous opioid system in the treatment community, will be important to the success of ALKS 5461. Within the context of this biology that the key attributes of 5461’s anti-depression activity and safety profile can be best appreciated. Regarding the NDA itself, during the third quarter, we completed our pre-NDA meeting and initiated the rolling submission of the NDA. The work that goes into submission of this magnitude is extraordinary and we’re making excellent progress. We have an ongoing dialogue with the FDA and the next module will be submitted to the FDA in next month and we will complete the submission in January. While our regulatory team is focused on preparing the submission, other works seem to be well underway as it’s prepared for launch. You can expect to be hearing more about ALKS 5461 in the coming month, as we continue to share data from the clinical development program, prepare the key manual scripts of peer review, and publication and the interact of the scientific and medical communities at multiple Congresses and of course prepare for an expected advisory committee meeting next year. Next let’s turn to ALKS 3831, a novel, oral, broad-spectrum antipsychotic candidates for the treatment of schizophrenia. We design 3831 to provide the antipsychotic efficacy of olanzapine while addressing the associated weight and metabolic liabilities by expanding olanzapine’s pharmacologic spectrum of activity to include opioid receptor modulation. We’re very pleased to successfully complete Enlighten-1, the first pivotal efficacy study, with a clear positive outcome. This was a critical milestone in the development program, which provides evidence of 3831 safety and efficacy as an antipsychotic agents both relative to placebo and the active compared to olanzapine. With that said in hand the focus of the remaining development program now shifts to the weight and metabolic properties of ALKS 3831. We are continuing to deepen our understanding of the mechanism of action of this new medicine and have semi dose and impacts olanzapine induced way to metabolic changes. We recently completed the 21 day Phase 1 from traditional medicine study 50 healthy volunteers evaluating the metabolic profile of ALKS 3831 compared to Olanzapine across a number of assessments including glucose, insulin and lipids. Our analysis of the data is at an early stage but the initial data we have received are consistent with our preclinical work and already suggest a number of important findings. First, the acute use of Olanzapine causes drug induce weight and metabolic changes. Secondly, [indiscernible] mitigates these abnormalities on a number of metabolic parameters. These findings recapitulate what we observed in our preclinical studies. We still expect to receive additional data sets related to lipid metabolism from this study later this quarter. One set that is in house and we've completed our analysis of the comprehensive data set, we look forward to presenting the findings of this informative study next year. I believe that these data are going to be very important in the understanding of the mechanistic foundation of ALKS 3831. Well, this mechanistic work is ongoing outside of the registration program, our second pivotal trial for ALKS 3831 in Enlighten-2 continues to advance. And Enlighten-2 is our Phase III study of assessing weight gain of olanzapine compared to ALKS 3831 over six months. We are on track to complete enrollments of this 540 patients study early next year with top line data expected in the fall of 2018. We believe that ALKS 3831 has the favorable way to metabolic profile that we designed from the outset and it will continue to reveal itself as we enter the final stages of the clinical development program. Now onto ALKS 8700 for multiple sclerosis. 8700 is also approaching the final stages of clinical development for registration and its unique safety and tolerability profile is now being borne out by clinical data. We designed 8700 with distinct physico-chemical properties to harness the efficacy of monomethyl tumorate or MMS with a differentiated safety and tolerability profile compared to TECFIDERA. Tomorrow at the European committee for treatment and research in multiple sclerosis medical meeting and other victims. We will present one month and three-month data from our ongoing, long-term open label safety study for ALKS 8700. The interim data, from more than 570 patients, demonstrated that ALKS 8700 was associated with low rates of gastrointestinal adverse events. The first three months are quite important clinically as this is when the majority of discontinuations due to GI tolerability occur with TECFIDERA. These data, which will be available tomorrow morning, will provide the treatment community with additional insights into the potential of ALKS 8700 to provide patients suffering from MS with an important treatment alternative. We will also present study design details from our ongoing Elekta Phase 3 study to evaluate the GI tolerability of ALKS 8700, compared to TECFIDERA head-to-head in approximately 420 patients. Enrollment is underway and we continue to expect initial data from this important study in the first half of 2018. On a regulatory side this quarter we competed as a key clinical requirements for NDA submission. Recall that the pivotal program for ALKS 8700 consists of two elements, pharmacokinetic bridging studies, enabling a 505(b)(2) regulatory pathway and data from a two-year safety study. During the third quarter, we competed the safety exposure requirements of 100 patients at one year needed for registration. We're competing a number of standard to inform studies for the registration package and we remain on track to submit the NDA in the second half of next year. Lastly, I'll provide you with an update on interesting developments on our ALKS 4230 program. This is our novel immunooncology candidate designed to selectively activate the intermediate affinity IL-2 receptors and potentially increase the number of tumor killing immune cells, as well as also improve tolerability compared to high dose IL-2. Our first-in-human clinical trial in patients with advanced solid tumors has been underway for sometime. We've been escalating doses of ALKS 4230, confirming safety in assisting pharmacodynamic markers to identify the optimal dose to advance into the dose expansion stage of those programs. To date, we have completed four dose escalation cohorts and sum of 24 patients have enrolled. The initial data are encouraging and provide evidence of ALKS 4230’s of dissipated pharmacological and biological activity. Data from the first four cohorts demonstrated dose-dependent pharmacodynamic effects on circulating CD8 T cells and natural killer cells with minimal and non-dose dependent effect on immunosuppressive regulatory T cells. This is the effect we are looking to achieve and clearly are now in the biologically active range of doses. We expect to present the complete dose escalation results at a medical meeting in 2018. In the mean time early next month at the Society for Immunotherapy of Cancer Meeting, a preclinical collaborator from the Cleveland Clinic, Dr. Brian Gastman will present interesting, new data on ALKS 4230 in the preclinical xenograft model of melanoma. Importantly this presentation will be made – will be the first to disclose ALKS 4230 effects in the tumor microenvironment. We’re continuing to build the body of evidence supporting the unique profile of 4230 and we look forward to advancing this program in the clinic in the coming months. So that is today’s update. We have a very robust development program underway here at Alkermes. To summarize each of these medicines have the potential to provide a clinically meaningful medical advance in their disease areas and reflects Alkermes commitment to developing patient-centered solutions. We’re making important progress across our top-line portfolio of candidates and I’m delighted to be part of this organization at this exciting time. With that I will turn the call back to Richard.

That’s great. Thank you, Craig. And I’ll finish quickly by simply saying that you can see that our development programs are advancing and 2018 will be a transformative year for the company with significant clinical milestones. We’ll enter the regulatory review phase with a careful launch of 5461, perhaps 3831 will expect to complete the pivotal program and report data from the six-month week study during the second half. For 8700, we plan to parent and submit the NDA. And for 4230, we expect to report proof-of-concept data and advance development program. Each of these has the potential to create significant value and we're gearing up for an intensive, active and exciting year ahead. So with that, I'll turn the call back over to Sandy for the Q&A.

Thank you, Richard. We'll now open the call for questions.

We'll now begin the question-and-answer session. [Operator Instructions] From JPMorgan, we have Cory Kasimov, Please go ahead.

Hey, good morning guys. Thanks for taking the questions. I have one on VIVITROL and one on ARISTADA. So I guess on first on VIVITROL, curious what you expect the impact of the recent head to head study of your product versus buprenorphine to be the one published in JAMA and then a follow-up on ARISTADA.

Good morning, Cory. It's Richard. I'll take then I will ask Craig at the end any point of view on it. But this study published last week in JAMA Psychiatry was the first head to head study of VIVITROL compared to SUBOXONE. And you’ve heard us saying in the past that we really to some of these head to head comparisons on this place because medicine as other observers have mentioned they’re diametrically opposite approaches to treating disease. With that said, it was a very positive day for VIVITROL because it showed equivalent efficacy to the – what’s considered to be the gold standard of treatment that is SUBOXONE. But importantly, what we’ve noticed in other commentators notes was the things that related to craving and particularly patient satisfaction that the treatment were quite high. So I think it’s another brick in the wall, another – another piece of substantial evidence from third-parties in a regular study showing that VIVITROL was mainstay medicine. Craig, do you have any thoughts?

Yes, I mean Rich what I would add to that is that I think importantly this adds to the well established efficacy profile that we’ve already seen with VIVITROL. So this is a study that was conducted independently of the company. And so, I think that’s an important point. But I think fundamentally and one of the most important tycoons for me is that it really bodes on the foundation of evidence that demonstrates the importance of a medication assisted therapies for these patients suffering from opioid use disorder. And I think it’s also important to note that there is no single treatment that is roughly every patients and that’s an individualized approach for patients is going to be important. And the patients get access to all FDA approved medications in the space, because they are all being underutilized. And so, this study addresses many of those questions and I think we'll see further data emerge later this year.

Okay, great. And then the follow-up on ARISTADA with regards to the Phase IIIb study you announced with ARISTADA and INVEGA SUSTENNA really what you are hoping to show with this trial. Is this designed to demonstrate non-inferiority and how long would you expect it to approve I believe it’s a 180 patients given that everyone will be going on to an active treatment.

So I'll – again Cory, I'll start on that one just as background. So in INVEGA SUSTENNA to those of you who don’t follow the call, is the – it’s the preeminent long-acting injectable product in the U.S. It’s about $1.6 billion drug growing rapidly. It has always had the most features in terms of its flexibility doses and durations and ease of use and initiation. So with the announcements that we made today, I think that we’ve leveled the plain field in terms of the features with our four week, six week, two month initiation dose and the ease of use in the clinic. I think we have a really strong product offering. What SUSTENNA has always had the oral around the system is viewed as the most efficacious of the medicines. And the data we presented in September and that I mentioned in my earlier remarks showed that that ARISTADA can provide excellent control for patients who are not getting adequate clinical satisfaction from INVEGA TRINZA i.e., our efficacy story on ARISTADA has always been extremely strong. This is a study that will manifestly demonstrates us in a setting that’s directly relevant to the treatment of this disease in the community particularly easy initiation with our initiation dose and then discharge from a hospital with two months of coverage in the community, which is a period this fight with risk for a patients we establish in healthcare in the community. So it’s both of an exclusive demonstration of our efficacy head to head versus SUSTENNA in a real world setting that is directly applicable to real life in the community for these patients. So Craig?

Yes, I absolutely concur what Richard just said. I think this is incredibly important study. I think one of the big challenges in the treatment of schizophrenia is adherence and relapse and so in a patient population that is acutely ill transitioning from hospital care into the community is a really important aspect to be studying. We believe that this new initiation regimen and the two in combination with our two-month dosage actually provides a cover for an extended period of time and a lot easy administration of ARISTADA. This particular study will basically answer both the questions on the initiation regime and will provide us data up to six months both the same group but also in comparison to INVEGA SUSTENNA. So overall I believe it’s an incredibly important study and important study for us to commit to.

And Cory on the timing, I’m not ready to say how fast it will enroll, we will launch the study in the next couple of weeks and like we always do, let’s see how the momentum builds, we can then project from the curve and we’ll give you guidance once we get underway.

Okay, understood. Thanks for taking the questions. I’ll hop back in queue.

Thanks Cory.

From Credit Suisse we have Vamil Divan. Please go ahead.

Hi, great. Thanks for taking my question. So one just on VIVITROL, I appreciate the comments you made but just in terms of the sort of current progress of the product you mentioned 5% sequential growth if I think there’s a $3 million one-time charge that lowered 2Q. So I just wanted to get a sense of what the dynamics for this quarter you mentioned inventory channel impact. Maybe if you could quantify that, take yourselves for lower growth in some of your key larger state. Just what sort of changed there to maybe impact the trajectory, it doesn’t sound like you are changing your long-term outlook but just is there anything that could impact the next few quarters going forward. And then I have one follow-up on after that. Thanks.

Sure, thanks Vamil, good morning. Yes, I think it’s important to look over time the VIVITROL as well as we've seen in the past. There are some fluctuations quarter-to-quarter and I think we expect to continue to see those. So this really 24% growth year-over-year we saw this quarter that’s what our projections would lead you for the balance of the year. And so looking at 30% year-over-year growth really, we’re just slightly down from where we started in the beginning of the year. But on a stage by stage basis VIVITROL is an unusual product. And there is every stage is a little different, we’ve talked about the ecosystems a lot and literally there can be county by county differences among the states. So when we looked at a variability this quarter, we didn’t see anything systematic. But there is a few issues that were affecting growth in some of our largest states. Some of them related to reimbursement, for instance in Colorado there was a change in the Medicaid payment vendors, which cause the delay and a disruption in payments throughout the state. So that affected growth. In Ohio, we saw more than 100% growth last year. There were some funding delays. Some state wide GL transition programs using VIVITROL were delayed until 2018. And a new drug core program was delayed, it start until September, so that growth in Ohio slowed to 40% this year versus over 100% last year. And then there is always the individual provider if you write when a key prescriber leads, a practice of retires are moves to the different ones that causes a drop in the overall prescriptions very quickly, but it takes some time for it to be built up. So VIVITROL sales are very concentrated. Its going to continue to fluctuate quarter-by-quarter, target predict in the short-term, but in the long-term we're very confident in the growth for the reasons we've outlined earlier today and then you know so well about VIVITROL.

Okay. All right, I also had a follow up on ARISTADA and just on this NanoCrystal dispersion filing. I just want to understand – because that means it looks like the one-time dose that you give in the startup treatment. So is this something that you just resource supplying of samples to be stock in position opposite when it's needed or just trying to understand that how to work commercially, what patients if you get a prescription for that and then get start – and then instructed product at that time.

Yes, this is absolutely a commercial embodiment. It’s a new product offering. And there will be certain patients who might be taking aripiprazole where the three months – three weeks orally in is not a problem, all they get the injection to continue the oral medication that’s what we’ve been doing up until this point. But for people who want to initiate quickly in the hospital without any fear or adherence this is an important new offering.

Okay All right. Thanks.

You’re welcome.

From Jefferies we have Biren Amin. Please go ahead.

Yes, thanks guys for taking my question. Maybe just on ARISTADA, I think you said your aripiprazole market share is 24% compared to 15% a year ago. So I guess, is this an expected trajectory that you thought you would achieve at this point. And when would you hope to achieve a majority share in the aripiprazole market.

I’ll say we’ve guided this year at the very beginning of the year to the idea of sales doubling. And as Jim reiterated that’s the track that we’re on. So it’s proceeding as we would have expected. But also what we knew that you all didn’t know at the beginning of the year is how we expected to built out this product family? And knowing that this initiation dose was coming and knowing what we were doing with the transition study from sustaining what we we’re doing, is we’re a building a stronger and stronger foundation year-by-year to support more growth as we go forward. So I do know when we’re going to cross 50%, but that’s our ambition and we're hard at it.

And then just on the traction for the more extended formulation for ARISTADA, what are you guys seeing out there. I know it’s early, but are we seeing pretty good traction with that formulation compared to the original formulation?

Yes. I think we're seeing two-month grow nicely. I would say we're at or head of our expectations. It's never going to be, as we talk about when [indiscernible] was launched its never going to be the – probably the broadest dose used. But and again, particularly in the study the transition if we can get people started in a hospital on two months, that transition to the outpatient care where most schizophrenics are taking care of on a daily basis is really, really important. And the losses in across all the LAIs frankly when people move into community based programs are dramatic. So we think that initiating earlier on with the two month potentially in the hospital with this that’s what we’re going to be studying is going to be an important factor to improve long-term use of LAI’s because still it’s under six months of therapy across the class which is not very good medicine. So we will be focused on that and the two months and the initial both coming this year. Now they’re both unveiled and people know about them, that’s a pretty exciting growth prospect for us, as we look at this franchise going forward.

And then just couple of things on the trails, Richard, I think you mentioned as X:BOT trial how does that design compare to the European study those published by JAMA. And do you expect that would be a bigger driver for VIVITROL and what percentage of prescribers apparently don’t prescribe VIVITROL because of the lack of a head-to-head versus the SUBOXONE.

So recall that the study XEPLION, the NIDA-funded study that was the head-to-head study of VIVITROL versus SUBOXONE. The design, I mean, it’s quite different than the European study only in the sense that patients were randomized in the XEPLION study before detoxification rather than after detoxification. And that sounds like a settled distinction, but it’s critical, because remember the people who wanted to go on Vivitrol need to go through detoxification. So if you get randomized with detox arm, before that happens, you could have a lot of drop out and people were actually in the study to get on buprenorphine. So we’ve registered our disagreement with the study design and I think that’s well-known out there. That said, just like you see with the tandem paper in JAMA Psychiatry, Vivitrol – it’s Vivitrol. So what we expect to happen in XEPLION is the Vivitrol will perform just fine. Patients who want Vivitrol and get that injection every month will be prevented from your last thing to opiod dependents. And what we saw in the TAM study there is underscored earlier was high levels of patient satisfaction with their treatment and this reduction of craving which is still important in the real world for patients. So we will look forward to seeing the data, but it’s – as I said each of these studies has its design limitations because fundamentally right you’re comparing two totally different medicines, one is an agonist, one is an antagonist, one requires detox, one doesn’t, it really is reflective more about the first – particular patient wants to do in the form of their own treatment, but all the data is important and I think we're just building a bigger evidence base for the use of MAT in general. Craig, do you want to add any color you had?

No. I mean I completely agree with what Richard has said. I think the challenges we faced are really that these medicines are fundamentally different. And so – design one trial that meets the requirements of all. I think the way that tandem approached his study where we had a very well controlled standardized detoxification regimen was ideal for studying the effects of VIVITROL. I think the way that – the X:BOT study has been designed – really allows for each study slides to use the standard practice and some patients would be enrolled in the study early in detoxification of this late. And so I think the important aspect here is that both studies are going to add to understanding of the value of medication assisted therapies. And I think both important for that reason.

From Cowen we have Chris Shibutani. Please go ahead.

Yes. Thank you very much. Some questions on VIVITROL. In the past you’ve described kind of the underlying drivers to include things such as number of key treatment providers, the number of patients each of the providers is taking care of the duration of treatment used. Can you comment upon any trends you’re seeing on any of those fundamental drivers and then I have another follow-up question.

Hi Chris, good morning. I would say that those trends are very much in line with what we've seen historically. For instance the number of providers is expanding at about 30% and so that fits in – that's another one of the ways we triangulate our expectations for growth in the long-term, because if that group of providers is still expanding. I would say just back to touch on Biren’s question as well. The number of the VIVITROL prescribers compared to the number of buprenorphine prescribers in users is quite low. Right, we have a market share below 5%. So as more and more data comes out, looking across the treatment areas, we expect our provider base to grow because VIVITROL is part – should be part of the standard of care as we've discussed. So the key metrics on VIVITROL are still growing very nicely and we'll continue to update you on those as if and when that changes.

And then as far as the contributing sub-groups of patient populations who are actually taking VIVITROL broadly speaking you in the past have characterized in terms of the Medicaid population growth in terms of units compared to the non-Medicaid private insurance group. Can you perhaps update us on what some of the trends that you are seeing there and what you are looking for in fourth quarter. And then lastly I know it’s not a significant portion, but obviously the treatment of alcohol addiction continues to be a component of the VIVITROL revenues was there any variability there that is going on that contributed to the weaker than expected third quarter results and lowering your guidance. Thank you.

Yes. I would say that maybe in reverse order, the alcohol growth again has been consistent for us. We think it is in that range 15% of the total usage of VIVITROL. That’s an area where we see potential growth as I think again people understand the safety and utility of VIVITROL and recognize that patient satisfaction on VIVITROL is actually quite high. So that’s a potential future growth area for us. I think as we look at – sorry, the first part of your question, remind me again on this.

The patient medicate versus non-medicate.

Well, patient medicate, sure, sorry.

Add on that, sorry.

Right, so to the gross-to-net have remained stable as has the growth in the medicate and commercial side roughly 50% of our patients are coming for the medicate side. And so, we haven’t really seen changes in those trajectories either. Again, I would say this is one where the idiosyncratic nature of the VIVITROL market on a state by state basis because a bit of a slowdown this quarter and really only because there’s two months left, we are brining our guidance down for the year. But we don’t have a real difference in the long-term growth prospects for VIVITROL.

From Leerink Partners, we have Paul Matteis, please go ahead.

Great. Thanks so much. A couple questions. Not to belabor the point on VIVITROL, but Jim I was wondering if you could kind of help us clarify how we should be considering the long-term growth curve. So I think the five-year CAGR is about 40%, year-over-year growth in 2015 was 57%, last year it was 44%. And this year with a new guidance its, it looks like it’s about something like 30% year-over-year. So just wondering if that reflects kind of a decelerating growth trends and what you are thinking is for sort of the next three or four years. And then I have a couple of quick follow-ups.

Yes. Thank you, Paul. I know I think you hit the growth numbers right. Our guidance does look at 30% growth. I think one of the things we've always said about VIVITROL is, it’s very difficult to predict in the short-term. And what we've done consistently is given you guidance expectations based on most recent growth expectations that we’ve seen. So I would say unequivocally that our long-term growth prospects for VIVITROL and our excitement about what this product can do and its importance in this field are not changed at all. We had seen a slight deceleration of growth which is why we adjusted our current guidance, but again against the backdrop of more data coming out, our own data coming out with ALKS 6428 program, the Tanum study, the X:BOT study coming and a broader appreciation that this – that what we're doing now in the opioid crisis isn't solving it. I think we view the long-term opportunities for VIVITROL as bullishly as we have in the past. But you're right this has been a slight growth quarter, a deceleration in the growth, but I would also say, take a look at the slides that we provided today with that quarterly growth quarter-by-quarter in the bar charts. We just have to be cautious not to make too much of the slow quarter either, and let's see how things progress through the rest of the year and into next year.

Okay, okay. Fair enough. Thanks, Jim. And then just a couple quick follow-ups, I know you talk about the tandem study and I know X:BOT will cover. I was wondering if you had any perspective on the study in addiction that was recently published, look at the cost effectiveness. VIVITROL I think it was murphy at all. And then just maybe if there is any quick update you can provide. I know in the 10-Q for 2Q you disclose that subpoena regarding from the U.S. attorney regarding documents related to VIVITROL if there is any update you can provide there. Thank you so much.

Yes. I might take that cost effectiveness paper which actually I think you have to read the whole paper to get an understanding of the study. The summary it doesn’t – in my view, it doesn’t actually reflect what the overall paper says. The other thing I think you have to keep into account that we've seen and others have seen is that patients generally on VIVITROL now are much sticker than patients on their broader standard practice. So one of the – I just think that’s a point and you’ll see more data coming out on that next year. But again patients on VIVITROL often have many other co-occurring disorders than patients that are looked at in the standard – overall pool of patients if that make sense. So I think also, you wouldn’t see these state programs expanding Paul, if – and frankly the success and the growth that we have in these state programs if those state providers medicate criminal justice system, jails, drug courts we aren’t seeing success. And it’s also very hard to count the economic value of having someone no longer addicted to opioids. You can look at health care utilization but there is a lot of benefits to having someone opioid free in terms of their employment, in terms of their jobs. We just don’t have a very good way of quantifying that right now and that’s something we’re also continuing to work on in the long-term. But I would just say, ask your family member, what it's like to have somebody free of this addiction, rather than into it and I think you get a lot more value added at than just some of the cost models that look historically that aren't really model for opioid dependence.

From Barclays, we have Douglas Tsao, please go ahead.

Hi, good morning. Thanks for the taking questions. Just in terms of the prescribers for [indiscernible]. Can you applied a little bit of context for how concentrated your doc position base is. And then just as a follow-up in terms of the guidance, we obviously had some reduction in topline expectation. So the cost guidance was basically maintained. So just curious in terms of how we should be thinking about sort of operating leverage and gross margins moving forward. Thank you.

Yes. In terms of the prescriber concentration, I mean I think that we’ve talked about obviously the difference between the number of prescribers for buprenorphine and for VIVITROL. I think our prescriber base is growing as I mentioned around 30% year-over-year. We gave some detail on that last year at our Analyst Day. So you roughly say 75% of the prescriptions are being driven by roughly 6,000 prescribers. I don’t think that’s terribly different from other specialty medication and as we continue to broaden the knowledge of and data that’s out there on VIVITROL. I think we expect that provider base to grow. In terms of the margins I think we're doing quite well this year. And the adjustment of roughly $10 million of that range, that just made sense, because as we brought the revenue range down. You simply didn’t have to change the percentage on cost of goods sold.

Okay.

We have time for one more question from Evercore ISI, we have Umer Raffat. Please go ahead.

Hi, guys. Thank you so much for taking my question. I wanted to ask a couple on ALKS 8700, one on VIVITROL and one on ALKS 4230, if I may. So maybe in a particular order, first VIVITROL just – Richard, I know you’ve commented on this in the past too. But consensus has 30%, 35% growth on the VIVITROL next year. And I’m just curious how you think about A, the ongoing rollout of new states, the new funding, but then also potentially new monthly buprenorphine is coming in. How do you think about growth over the next couple of years? And I understand choppiness near-term, but over the next year-to-year, how do you think about a stable run rate on growth rate. What’s that number to you one. On ALKS 8700, your ECTRIMS presentations has no serious GI, AEs and 0.5% GI discontinuations, but I’m curious what’s the comp in your mind for TECFIDERA, because the other thing we noticed the flushing looks kind of comparable, so we just curious, I guess thinking about the first month worth the GI data at Alkermes, as well as I know you’re tracking efficacy on ALKS 8700 any preliminary read on what the event rate is on relapse in this open label trial? And then finally on ALKS 4230 ask that the – if it just anti-tumor activity or is it just T-cell activation either you are going to show data on anti-tumor activity as well? Sorry about the lot of questions. Thank you.

No, that’s good – those are excellent questions. I’ll try to remember them all and answer them all. So on the VIVITROL and I don’t understand defensive about this, because I think it’s just really a statement of fact about how unusual this product in such an unusual market. Because the growth is so dependent upon the combination of the classic things of one would do and introducing a new pharmaceutical product to a physician community, but also these huge tectonic plates of public policy. Later today, the President is going to announce things that the administration is going to do about this present, to the Christie commission next week or the first week of November is going to put their report for, then you ask, okay, what – how is it we’re going to change in response to that, to deal with an epidemic where 60,000 people are going to die. So the over – the cone of possibilities for VIVITROL with under 5% market share in the face of a national epidemic is incredibly broad. And I almost hate to express it in terms of growth in that way, because what it really it’s responding to a tragedy that’s happening in this country. And the TanDEM data and the X:BOT data are just underscoring the effect of VIVITROL. It went from being a complete peripheral unknown medicine to becoming increasingly a main stage medicine in addressing this epidemic. So we're building more production capacity for 2020 and beyond. We are really strongly committed to making sure this medicine gets to the patients, who really need it. So it's hard to put in numeric growth on it Jim, so we really just swing wine divine often said. As we get in new information, we share with you guys and we guide to the next quarters, the next period and we're super transparent about it, recognizing that there's a whole lot of potential outcomes ahead. But the medicine is incredibly important, it’s increasingly supported by more and more data. The critics who say that there's a positive of data are slowly being retired and so here we are and we're quite optimistic about where it's going to go from here, because we're quite committed to the value of this medicine for patients. On the long acting injectable bup, so we think those are important medicines. And I think it has a salutary effect in the market more doctors are trained to access branded medicines from specialty pharmacies and give injections and monitor patients on a monthly basis. That's exactly the type of medicalization of this treatment paradigm that is necessary for more expanded use of VIVITROL. ALKS 8700, I’ll let Craig put any color, but the comps you can decide, you’ll see yourself. We're going to – we'll show you the AE data in the one and three-month period, I think it speaks for itself and you see it’s quite positive. The flushing piece that was important, because the systemic – the flushing is on the systemic side that’s on – that’s outside of the GI. And we’ve seen equivalent flushing, which is what we predicted because the MMS, the active of this is doing the same thing on the systemic side that we believe TECFIDERA and MMS will be doing. So the action is on the luminal side, on the GI side, where we think we got a differentiated product for the various reasons we designed physicochemically into the molecule. And in terms of the efficacy data, I don’t – actually don’t know the answer to that question. I’ll let Craig to that, but we’re not going to provide any efficacy data obviously tomorrow from an open-label safety study.

Yes. So just to add to what Richard has already said, I think the data that you will see presented tomorrow I think are incredibly impressive from a GI perspective. We do think they differentiated and are well below what we would expect to see with TECFIDERA. In terms of the long-term data, we – as you know we're collecting data on relapse as well as MRI and it's still the premature for us to be able to comment on that. And sinusoidal mature, those will be presenting those data and will be able to speak today.

On 4230, presentation work on preclinical models looking at the effective of 4230 on infiltrated – in the tumor microenvironment. So its just another piece of the story about what the medicine history in vivo. I just want to make sure, you didn’t confuse that – that won’t be human data – the human data will come later in 2018 as we complete that escalation cohort.

Thank you.

You’re welcome.

I’ll turn it back to Sandy for closing.

Great. Thanks everyone for joining us on the call today. Please don't hesitate to reach out to us or the company if you have further questions.

Ladies and gentlemen, this concludes today's conference. Thank you for joining. You may now disconnect.