Alkermes' (ALKS) CEO Richard Pops Presents at Alkermes Conference Call to Discuss FORWARD-5 ALKS 5461 Data (Transcript)

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Alkermes plc (NASDAQ:ALKS)

Alkermes Conference Call to Discuss FORWARD-5 ALKS 5461 Data

October 20, 2016 5:00 PM ET

Executives

Eva Stroynowski – Director-Investor Relations

Elliot Ehrich – Chief Medical Officer

Richard Pops – Chairman and Chief Executive Officer

Analysts

Paul Matteis – Leerink Partners

Whitney Ijem – JPMorgan

Umer Raffat – Evercore ISI

Vamil Divan – Credit Suisse

Chris Shibutani – Cowen

Biren Amin – Jefferies

Liav Abraham – Citi

Ami Fadia – UBS

David Risinger – Morgan Stanley

Operator

Welcome to the Alkermes Conference Call to discuss the result of the FORWARD-5 study. My name is Katie and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being recorded.

And I will turn the call over to Eva Stroynowski, Director of Investor Relations. Please go ahead.

Eva Stroynowski

Welcome to the Alkermes plc conference call to discuss the results of the FORWARD-5 Phase 3 study of ALKS 5461. With me today are Richard Pops, our CEO; and Elliot Ehrich, our Chief Medical Officer.

We will be making forward-looking statements based on our current expectations relating to, among other things. The future clinical development of ALKS 5461 its therapeutic value and commercial potential and our regulatory filing strategy. These forward-looking statements are neither promises nor guarantees and are subject to a high degree of uncertainty and risk.

Please see our press release issued today and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those projected or suggested 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.

After our remarks, we will open the call for Q&A. Now I'd like to turn the call over to Elliot.

Elliot Ehrich

Thank you, Eva. This afternoon we announced positive top-line results from FORWARD-5 and this is really exciting for us here at Alkermes. So FORWARD-5 evaluated ALKS 5461 as an adjunctive treatment for major depressive disorder in patients with an inadequate response to standard therapies.

In the study ALKS 5461 achieved statistically significant efficacy on the primary endpoint of improvement in depression scores. The data are clear in ALKS 5461 behaved in a manner consistent with previous studies. With the most recent data in hand along with significant amount of other data supporting the efficacy, safety and tolerability of ALKS 5461 our next steps are to request a meeting with the FDA and prepare to submit a new drug application for this fast track designated medicine. Then before I get into the details, let me provide some background on ALKS 5461 and the FORWARD program.

ALKS 5461 is the centrally acting opioid modulator based on a foundation of neuroscience and pharmacology. It is a fixed dose combination of buprenorphine, which is a partial opioid agonist and samidorphan, a potent opioid antagonist it’s administered orally once-daily in a sublingual bilayer tablet. FORWARD-5 was a Phase 3 randomized double-blind placebo-controlled study. That evaluated the safety, tolerability and efficacy of two dose levels of ALKS 5461, our core dose of 2mg/2mg which we investigated in multiple studies now and a lower dose of 1mg/1mg. The 1mg/1mg and 2mg/2mg refer to the doses of buprenorphine and samidorphan respectively in milligrams.

The study randomized 407 patients who had a diagnosis of major depressive disorder and despite treatment with SSRIs or SNRIs had persistent depressive symptoms which were defined as Hamilton Depression Rating Scale Scores or HAM-D of 18 or greater. All patients remained on their background antidepressant therapy throughout the treatment period and they received their adjunctive ALKS 5461 or a matching placebo tablet. The study employed a sequential parallel comparison design or SPCD. That was very similar in construct to what we used in the two previous studies. FORWARD-4 as well as a successful Phase 2 study which we refer to as Study 202.

FORWARD-5 involved two randomized double-blind stages run in sequence. Stage 1 was 5 weeks long and Stage 2 was 6 weeks long. Stage 2 of an SPCD study randomizes only those patients who did not respond to placebo in Stage 1. The primary endpoint of an SPCD study is evaluated by averaging the results from Stage 1 and Stage 2. The FORWARD-5 study was positive, the of 2mg/2mg dose of ALKS 5461 demonstrated statistically significant reductions in average MADRS-6 scores from baseline compared to placebo with the P-value of 0.018. MADRS-6 measures the core symptoms of depression and was the pre-specified primary endpoint. ALKS 5461 2mg/2mg also demonstrated significant improvements in the full 10 item MADRS scale with the P-value of 0.026.

The 1mg/1mg dose of ALKS 5461 showed activity with improvement in depressive symptoms though the improvements did not achieve statistical significance. These are the similar results which we’ve just received. We’ve got a lot of data to look at and go through and analyze and we’ll present a more complete data picture at future scientific meeting.

Turning to safety and tolerability, the importance of a favorable safety and tolerability profile should not be underestimated in the case of a new potential treatment option for depression. FORWARD-5 provides additional evidence of 5461 safety profile. Overall 83% of the patients completed the study and that's very good for a study of this duration. ALKS 5461 was generally well-tolerated and the most common adverse events were nausea, dizziness and fatigue. The events were generally mild, transient and occurred around the time of treatment initiation.

Importantly, there is no evidence of withdrawal for patients stopping out 5461 of the study nor was their pattern AEs that would be indicative of abuse potential. The clinical development of ALKS 5461 has been a steady process of experimentation and learning. In January, we announced the top line results of the FORWARD-3 and FORWARD-4 efficacy studies. In June, we presented the data from these two studies at the American Society of Clinical Psychopharmacology or ASCP Conference.

In September, we went with a division of psychiatric products at the FDA and reviewed the data from the FORWARD-3 and FORWARD-4 studies. FORWARD-4 was a negative study based primarily on the selection of a single time point for the primary analysis. Overall the data provided strong evidence, a supportive evidence of ALKS 5461 at the 2mg/2mg dose. FORWARD-3 was less informative despite a relatively consistent effect of ALKS 5461 and this was due to the high placebo response observed in the study.

Taken together the datasets from the two studies provided us with a wealth of knowledge we could apply to FORWARD-5 particularly related to the statistical analysis plan. In order to avoid the risk of determining success or failure based on a single time point in an inherently variable disease. We pre-specified the primary endpoint for FORWARD-5 is the change in depression scores from baseline to an average over the final weeks in the two stages.

The continuous measurement of efficacy across multiple time points is a more powerful and precise depiction of the drug's efficacy profile. In addition to that change, we chose to use the six item Montgomery-Asberg Depression Rating Scale or MADRS-6 as our primary efficacy assessment. MADRS-6 focuses on the core symptoms of mood and excludes symptoms that are commonly observed in other disease states were that may be attributable to background therapy.

As a result MADRS-6 may provide a more specific measurement of antidepressant activity. That I described earlier the study also achieved significance on the MADRS-10 as well as MADRS-6. We submitted our statistical analysis plan for FORWARD-5 to the FDA. The agency did not provide feedback on a stat plan prior to unbinding of the data this week. However, they acknowledge receipt of the plan and are aware of our approach. And we will discuss the results of the entire FORWARD program at our next meeting.

Each of the studies in the FORWARD program contributes data useful in assessing the safety and efficacy of ALKS 5461. On a standalone basis and taken collectively. For this reason we also pre-specified a statistical plan for pooling data from FORWARD-5 and FORWARD-4 which shared a similar design. We've just started this work but the initial results are powerful, the sample sizes increased P-values drop. This underscores the informative power of a large dataset as well as ALKS 5461’s consistent anti-depressive effect which we will be presenting these data to the FDA in the future and to you.

With today's results confirmatory data from Study 202 supportive evidence from FORWARD-4 and data from more than 1,500 patients. We believe that we have a robust body of evidence to support a regulatory submission for this important new medicine. We’ll request a meeting with the FDA very soon and map out the next steps with the goal of bringing this potential new important treatment option to patients as soon as possible.

Before I turn it over to Richard. I'd like to offer my sincere thanks to all of the collaborators involved in the ALKS 5461 FORWARD program and to all of the patients who participated in this important research. This is a substantial undertaking. And we are deeply committed to it. We very much hope this research will translate into benefits for all of you and others in the Mental Health Community. I’d also like to recognize all of the Alkermes’ employees who contributed to this development program their dedication, persistence and thoughtful execution help to drive a successful outcome.

We share a common goal with our collaborators and colleagues in the treatment community to have a profound impact on the treatment of major depressive disorder. With a novel mechanism of action and a large foundation of clinical data now in hand, we believe that ALKS 5461 has the potential to achieve this goal.

With that, I’ll now turn the call over to Richard.

Richard Pops

That’s great. Thank you, Elliot. Today’s news is an important milestone for ALKS 5461 and for Alkermes as a company. It’s really gratifying to see years of hard work realizing the successful outcome. And I’d like to thank Elliot and join him and thanking our collaborators, employees, patients and families involved in these studies. This is a tough area for drug development. You’ve heard me say in the past that successful drug development in psychiatry requires three things. A strongly active agent, a modern clinical trial designed to minimize placebo response, and careful execution across multiple sites. We’ve been learning and adapting along the way.

ALKS 5461 exemplifies our philosophy and approach to drug development. We focus on those diseases that affect millions of patients, where many medications are available yet it remains a tremendous amount of suffering. We set a high bar for ourselves recognizing the successful new medicines need to have clear differentiating features clear to patients, to physicians and to payers modest advances are not enough. ALKS 5461 is based on a new mechanism of action. And it’s designed specifically for those patients who are not getting adequate clinical relief from first-line treatments for major depressive disorder.

There are millions of patients in this category each year in the U.S. Reflecting the reality the depression causes one of the greatest burdens of suffering and cost of any disease. Of the 11 million people in the U.S. treated with antidepressant medications approximately 7 million failed their first therapy and 5 million failed their second. This is an enormous population of patients in an enormous current unmet need. We couldn’t be more excited to see the clear and compelling efficacy results announced today.

In addition to demonstrating ALKS 5461’s efficacy and improving depressive symptoms the data reiterate the favorable safety and tolerability profile that we’ve seen today with ALKS 5461. Coupled with the results of the human abuse potential study we completed last December, we now have a comprehensive set of safety data that showcase a consistent safety profile with a lack of abuse potential. This is an important medicine for patients truly suffering from a difficult disease. And we’ll move forward now expeditiously to pursue a regulatory submission.

I’ll finish there and I’ll turn it back over to Eva to manage the questions.

Eva Stroynowski

Thanks, Richard. We’ll now open up the line for questions. Operator?

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] And our first question comes from Paul Matteis from Leerink Partners. Please go ahead.

Paul Matteis

Great. Thanks very much for taking the questions and congrats on the results.

Richard Pops

Thanks, Paul.

Paul Matteis

I have a few if you don’t mind. My first one is that Rich, can you remind us what the prior FDA feedback was on the use of SPCD and how the agency views that trial design since it’s never been used to support registration before.

Richard Pops

I’ll make an introductory comment, Paul. And then I’ll let Elliot who’s the expert on this. But there has been enormous amount of discussion about SPCD even in March of this year kind of a summit meeting was held at FDA with academia and industry participants because the focus in the whole field is minimizing placebo response in these clinical trials and SPCD is a critical element of that. But Elliot, I’ll let you elaborate.

Elliot Ehrich

I’d echoed that as well. So there is great interest at the FDA in the treatment community and in industry in terms of minimizing placebo response and the FDA is quite interested in SPCD we had a big conversation in Bethesda earlier in the spring which they attended. We have met with the FDA and they have – we’ve given our plan and we’ve surrounded our plan with a great deal of statistics to demonstrate our implementation of SPCD and they have agreed to its use. So we are – we remained our results are good and consistent, so we believe it’s sufficient for this package.

Paul Matteis

Okay. Thanks, Elliot. And then I’m curious I know the MADRS, the full MADRS and the HAM-D 17 has supported approval of antidepressants has the MADRS-6 ever been used before to support registration?

Elliot Ehrich

Just to remind you, we hit on both MADRS and MADRS-6 in this study.

Paul Matteis

Right.

Elliot Ehrich

But we decided – we decided to focus the primary on the MADRS and it’s not been used as a primary endpoint before but it has been specifically invoked in the context of adjunctive treatment. And it focuses on the core symptoms of depression and there is when people look at adjunctive treatments if someone’s asking are you just helping sleep or some of these accessory symptoms and the MADRS-6 provides that assurance that we’re really going after core depression that this is an adjunctive treatment agent. So it’s actually – there’s actually a very strong rationale for its use.

Paul Matteis

Okay, thanks. And then maybe just one more quick one. Could you – are you willing to expound on the magnitude of the effect size and maybe put it into context number of points drug placebo difference and how that looks compared to other drugs that have attained approval?

Richard Pops

Yes, this is literally just coming off right now. We have the top-line results and we’re going to be digging into the specific changes and the effect size, this is SPCD so we’ve got different stages. We have some work to do. But we will ultimately be presenting that data.

Paul Matteis

Okay, okay. Thank you very much.

Richard Pops

Great, Paul. Thank you.

Operator

Thank you. And our next question comes from Cory Kasimov from JPMorgan. Please go ahead.

Whitney Ijem

Hi, guys this is Whitney on for Cory. First just a couple of timing questions I guess I believe you guys have fast track designation here. So is there any color you can give us on when you might think you will be able to get in front of the FDA even if it’s sort of broad strokes guidance?

Richard Pops

Well, I think they will request a meeting within a matter of a few days or a couple weeks. As Elliot said, this is literally hot off the presses. So this is the primary analysis of the primary endpoint, we’ve got it out to you all will finish the full analysis we’ll request the meeting and I imagine that we’ll see them what would you say, Elliot, we will probably see them early in the first quarter.

Whitney Ijem

Okay, that’s helpful. And then assuming you get the go ahead. I guess how quickly could you turn around and file or how much work to be done ahead of time to kind of prepare for that?

Richard Pops

But we’re preparing the NDA now and obviously we have a lot of work to do. So we’ll make a more firm call and a filing date when we come out of the FDA meeting. But we’re activating now.

Whitney Ijem

Got it. And then the last one from us is just assuming this does make it all the ways through. How much of leverage do you have with the existing ARISTADA commercial infrastructure? And how much would you need to add?

Elliot Ehrich

It’s an interesting question. It’s a good question because we’ve actually with VIVITROL and ARISTADA kind of hitting their strides now we have a very significant national commercial infrastructure. We’ve said in the past, and we can’t really hold us to this. But we think we need to layer on another sales force for major depressive disorder adjunctively. But that might be on the order of 300 people or so.

But this commercial infrastructure that we have in place in terms of our medical affairs and our marketing commercial infrastructure that’s all in place so we have a significant amount of leverage to add additional products.

Whitney Ijem

Great. Thanks for taking the questions and congrats.

Elliot Ehrich

Thank you.

Operator

And our next question comes from Umer Raffat from Evercore ISI. Please go ahead.

Umer Raffat

Hi, guys thanks for taking my question and congratulations on the data. Perhaps first Elliot, what’s the P-value on MADRS-6 in the prior FORWARD-4 trial. I just wanted to make sure we understood if FORWARD-4 has a P-value less than 0.05 or whenever the P-value is on MADRS-6 in that trial number one.

The second thing you mentioned was when we pull FORWARD-4 and FORWARD-5 only those two trials we’re seeing static. So I just want to confirm is that what you said and also are you pooling the whole trial or just the Stage 2 of both trials, that’s the second. And third, what if we count FORWARD-3 in there also. So what do we get then? And what does the FDA want? Thank you very much.

Elliot Ehrich

Okay. So I’m going to do my best, Umer to get your questions. The first question is about statistical significance of MADRS-6 in the FORWARD-4 study. And I don’t have that specific number with me but it was significant in that study.

Richard Pops

The pooling.

Elliot Ehrich

Yes, the pooling – so that’s really one of the beauties of this part you know both – the individual SPCD studies are very economical. And so again, this additional look at consistency and power as we bring those two together and the initial was actually going to be looking at pooling both of the studies across both stages and then we will follow that with looks at individual stages.

Umer Raffat

And FORWARD-3 is not included…

Elliot Ehrich

FORWARD-3 is different design, yes, we can’t really use that. But it is a really nice facet of the program to have both the individual studies and to be able to show this consistency of effect that becomes magnified when you pool the two studies together. And that was…

Umer Raffat

Got it, but Elliot in the – sorry, in the scenario, where you pool FORWARD-3, FORWARD-4, FORWARD-5 and Phase 2 is that P-value of less than 0.05, so from Phase 2 all the way to FORWARD-5?

Elliot Ehrich

Again that's – that the studies each have there are some differences for example between the individual weeks as it relates to the Phase 2 study and there are just in the functional study design and FORWARD-3 has a different design. It only has one stage. So we've not done such an analysis. And I'm not sure how quite how meaningful it would be. But what you are actually getting to is a very important point which is that, what we do see is study after study after study. We're seeing this consistent efficacy effect and that really is – that really adds to the overall assessment of the robustness of the finding of antidepressant activity of ALKS 5461.

Umer Raffat

Got it. Thank you very much and congrats again.

Elliot Ehrich

Thank you.

Operator

Thank you. And our next question comes from Vamil Divan from Credit Suisse. Please go ahead.

Vamil Divan

Great, thank you. And thanks for taking my question. So just two if I could and most of mine have been asked already but just if you had to do more work after meeting with the FDA and do another study just like FORWARD-5 how long do you think that would take you to execute. So when would that study be completed. And then just on the MADRS-6 could you maybe just give us a little bit more color on what you mentioned as statistical benefit, we’ve seen here but just in terms of what's clinically meaningful. What degree of change would you say is a clinically meaningful impact on MADRS-6? Thank you.

Richard Pops

Yes, so we really right now in terms of the additional – so we've got a very strong body of data across the studies. So we don't have plans to conduct an additional study. We made continue to explore ALKS 5461 in other psychiatric indications the opioid system is implicated in autism, in OCD and in anxiety and a variety of disorder. So there's more work that we can do over the longer term in terms of MADRS-6. The key thing is that what it does is it takes out some of the more somatic aspects of the MADRS scale. So through the things like sleep or excludes some GI symptoms and what it does is focus really in on the core symptoms of mood and how patients are experiencing life, energy, motivation et cetera.

And why it is so important because you could for example come up with a drug – you could actually give someone a very potent sleeping agent and their sleep symptoms might improve but you would be doing a darn thing for their depression. And so the MADRS-6 helps to give you a more focused look and then really in doing so it filters out some of the noise of these background symptoms or symptoms that can be affected by other elements of the background therapy.

Vamil Divan

Okay. Maybe I guess that’s my first question different way then. Could you just remind us how long it took you to execute on FORWARD-5 sort of from the start of the study to totally?

Richard Pops

How long the FORWARD-5 take to do? So we enrolled that study in about I’d say about 18 months and it's as about – it has 10-week in life a period and then we – a very efficient data cleaning. So you can kind of add those I’m going to give you a rough number.

Vamil Divan

Okay. All right, thanks.

Richard Pops

Okay.

Operator

And our next question comes from Chris Shibutani from Cowen. Please go ahead.

Chris Shibutani

Thank you. Congratulations on your diligence and continuation of positive data. Two questions, one with the explanation of how you modify your statistical analysis endpoint plan. Did I hear correctly that rather than just taking your data endpoint at week five or six that there was an averaging of time to clarify exactly what you mean by that. And when you describe combining with lots of different studies are you using this averaged endpoint measurement time when you speak to that analysis that you've done so far?

Elliot Ehrich

So to be clear – depression is a disease that has a subjective endpoint. Its variable people feel different from week to week and you and there's an inherent variability or week to week variability in responses. And so it actually makes a lot of sense it rather than sort of focus on one week. What one does and what we did was in modifying the statistical analysis plan, of course they let's look – let's look at over multiple weeks. And so the analysis – what the analysis plan does is it takes that in Stage 1. It takes the change from baseline to week three, to week four and week five and then averages those. And in Stage 2 it takes does the same averaging the individual change from baseline from weeks three to six. And that's your Stage 2 analysis.

And then consistent with the overall SPCD analysis plan then you average those together. So at the end of the day, we're bringing a lot of data into the primary analysis and it reduces variability that gives you a much more precise and accurate look at the antidepressive effect. So it just makes a ton of sense to do.

Chris Shibutani

Right. The logic behind it seems to make sense but then to be clear the way FORWARD-3 and FORWARD-4 were analyzed and when those results were presented at the beginning of the year that averaging of those time courses was not the way the results were determined, is that correct?

Elliot Ehrich

That's correct. As you heard – I’d say this has been a path of experimentation and learning. And that was a key learning from those initial FORWARD-3 and FORWARD-4 studies. That we wanted to – it really the primary reason that FORWARD-4 didn't work with the specific week that we chose but if you looked overall like many other time points. It was a very strongly positive study. So we took that learning and applied it to the analysis of FORWARD-5.

Chris Shibutani

And then as a follow-up question. I recall after FORWARD-3 and FORWARD-4 were presented in June at the clinical pharmacology meeting there was much discussion over possibly what factors could it contributed to the failings of FORWARD-3 and I believe one of the proposed hypotheses stem from the question of whether the placebo responders I mean not have been filtered out as well. I know that you said that were just hot off the press and you haven't given details but do you have any sense whether that interpretation perhaps continues to ring true when you think about FORWARD-5 and maybe the portion of patients that were effectively spring down in essence using the Stage 1 and Stage 2 methodology.

Elliot Ehrich

Yes. The SPCD designed worked it did screen out patients and that was a key. There was – that we know and we do have a bit more work to go into – to dive into the data. What we like actually you said right now we're talking just about the overall dataset and how it worked together but again there is this consistency what we learned and the function of SPCD in FORWARD-5 we were able to recapitulate in the – in FORWARD-4 we’re able to recapitulate and FORWARD-5.

Chris Shibutani

Thank you for the questions.

Elliot Ehrich

Thank you, Chris.

Operator

And our next question comes from Biren Amin from Jefferies. Please go ahead.

Biren Amin

Yes. Thanks for taking my questions and congrats on the data. Elliot, have you got the sensitive analysis of the difference that week six versus baseline in Stage 2 and week five versus baseline in Stage 1?

Elliot Ehrich

We're really just at the beginning here we've not done those we've not done the sensitivity analysis but we've got we have a lot of work ahead of us. And again we'll be putting a larger data package together and disguising it both with the FDA and presenting it at the upcoming scientific meeting.

Biren Amin

Okay. And then I guess just on the average from – the data from week three to week six on Stage 2. Was the treatment difference consistent across each of the weeks versus placebo or do you see some noise week to week?

Elliot Ehrich

We can see. I mean we just looking at the graph as it coming out. There's ALKS 5461 consistently beats placebo across the treatment periods in both stages. And that's what we're building on as you see the results.

Biren Amin

Got it. And I know Chris asked this, but let me ask it in a different way. How many patients in Stage 1 are considered placebo responders?

Elliot Ehrich

Well, I don't have that data. I don't have that data yet.

Biren Amin

Okay.

Richard Pops

Yes, that would be something Biren, I mean in our presentation like you said ASCP will give you all.

Elliot Ehrich

Yes, you get the whole.

Richard Pops

But I think that the point is that SPCD works the filtration was superior to what we saw in FORWARD-3 and I think that's a large reason why this study is successful.

Biren Amin

Okay. And I guess maybe one last question. Is there any opportunity for European filing?

Richard Pops

Well, I’ll let Elliot, our plan had been if you read the guidelines for adjunctive antidepressant therapies in Europe they require a different study design and are plan was to complete the FORWARD program see where we stood vis-à-vis the total dataset. And then go back and seek scientific council in Europe. But for the purposes of this conversation, I assume that this is mostly U.S. focused and our filing strategy right now is focused on the U.S.

Biren Amin

Got it. Thank you.

Richard Pops

You're very welcome.

Operator

And our next question comes from Liav Abraham from Citi. Please go ahead.

Liav Abraham

Good afternoon, and let me add my congratulations as well. Most of my questions have been answered, but just going back to some of the previous questions. Can you and this has been asked but perhaps can refine it. But I’d be interested in the magnitude of placebo response between those trials FORWARD-3, FORWARD-4 and FORWARD-5 anything incremental you can sound that would be helpful. Thank you.

Richard Pops

That’s a whole – so your question is right on in terms of that’s the whole game in depression – I think it’s probably the highest level of difficulty of any indication that’s out there. Right now in the whole game is controlling a placebo response. We have we clearly with the SPCD we control the placebo response and as we come together and put all the data together. I think you’ll see that when we present that data. And again that’s really it’s that Stage 2 where we – after we’ve done a filter where you’re able to see that affect.

Operator

Thank you. And our next question comes from Marc Goodman from UBS. Please go ahead.

Ami Fadia

Hi, this is Ami Fadia on for Marc. Could you give us a little bit of a background on how you came up with this pool data analysis plan and if you had a chance to discuss some of this with the FDA? And what if when you meet with the FDA and if they do not accept this, would you be willing to run another Phase 3 study? Thanks.

Elliot Ehrich

So to be clear, the pool of data analysis plan which was pre-specified is supportive evidence. It provides yet additional data to show the efficacy in the consistent of efficacy of ALKS 5461, but the core of this program is based on individual positive studies. The 202 Study pre-specified very positive study, the study FORWARD-5 that we’re discussing today and then FORWARD-4 which is – which shows strong supportive efficacy. So we have a package the pool analysis provides an additional look and an additional way to communicate the robustness of the treatment effect of ALKS 5461.

Eva Stroynowski

Operator, we have time for one more question, sorry, Ami…

Ami Fadia

No, could you just answer the second part of the question, whether you’ve had a chance to discuss this data package with the FDA at least the approach of it. And at this point, if the FDA does not accept the pooled analysis or the data package as it is. Would you be willing to run another Phase 3 study?

Richard Pops

I mean this is Rick, let me just make sure because the way you have the questions, is just that maybe you didn’t understand the answer we just gave, which is the pooled analysis is independent of the data submission we were put in the NDA. We would expect FDA to do this pooling themselves with all about this question, when you have 1,300 patients worth of data and there’s so much robustness there’s way to testing for consistency and the internal consistency between the various studies. That’s part of the rigor of analysis of the new drug application.

So we expect to file and propose to file based on as Elliot said, two randomized controlled positive studies, supportive study from FORWARD-5 and the totality of the 1,500 patients who studied with 5461. And we think that’s a very strong package. The other point is always worth reiterating with 5461 and in the treatment of depression in general, it’s about risk benefit and that speaks to the tolerability and safety of the agent. Elliot mentioned in his earlier remarks, but it’s worth noting, this is really well-tolerated medicine. And I think it’s going after patient population for whom their next alternative is to proceed to anti-psychotic drugs, electroconvulsive therapy or other more poorly tolerated modalities. So we think there’s a really strong rationale for the use of this, which is precisely why we developed in this way in this patient population.

Ami Fadia

Thank you.

Operator

Thank you. And our next question comes from David Risinger from Morgan Stanley. Please go ahead.

David Risinger

Thanks very much. I wanted to add my congrats as well. I’ve got a couple of questions. First, could you just frame for us what your view as a clinically meaningful improvement.

Richard Pops

In depression, that’s a really that’s a tough question to answer. And the reason being that you know a clinically meaningful improvement is various depending on study design, filtering placebo patients or not and it’s also influenced heavily by the degree of placebo response with an individual study. So as our first line in these studies one looks for statistical significance and robustness of the finding.

Elliot Ehrich

Can I just add to that? Dave, I think some of the audience may not remember that, Dave this is happening at the backdrop of placebo responses are going to be measured when you see the figures. These are very significant drops in depression scores in some patients in placebo arms. So in many ways the convention is statistical separation from placebo, almost irrespective of the numeric value because the numeric delta is often driven more by the placebo response then by the active.

David Risinger

That’s very helpful. And then just to help us, I guess, think about it. So obviously you’ve already presented some SPCD design results and so on and so forth. But with respect to the filtering and basically the minimization of the placebo response, any suggestions for comparing your dataset when we see it next year, for example to I don’t know the J&J, as ketamine [ph] dataset when that comes out. I think their results are due in 2017 as well.

Elliot Ehrich

I mean they are using a similar type of design in their program, but I would I think one would avoid making direct comparisons really apples and oranges kind of situation. That’s a an injectable, sorry it’s an intranasal, but it has to be given in a doctor’s office under supervision. And so it’s really – it’s just this is an oral once-daily taken as an outpatient different patient populations, I don’t think that one could really make a meaningful comparison.

David Risinger

Got it. Thank you very much.

Elliot Ehrich

You’re welcome.

Operator

This concludes the question-and-answer session. I’ll now turn the call back to Eva Stroynowski for closing remarks.

Eva Stroynowski

All right, thanks everyone for joining us on the call today, please don’t hesitate to reach out to us if you have any additional questions.

Operator

Thank you, ladies and gentlemen. This concludes today’s call. Thank you for participating. You may now disconnect.

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