An on topic post! I’ll bite (no pun intended)...

3/13: Cowen’s conference
3/18: ACC presentation
Present - 3/31: sNDA filing
5/31 (or sooner): Notification of application being granted priority review (if we receive it)

I also believe Amarin will announce timing of EU MAA filing soon, and it will be submitted no later than end of 2Q. This might be considered a catalyst, as I think the quick timing may surprise people.

Thoughts? I probably have forgotten a few things.

Sts, you had it right that companies often interact w/ the Agency ahead of regulatory submission, and a pre-NDA/sNDA meeting is a good example of this. In these cases, the company would likely have a better idea of their prospects of receiving priority review. These types of meetings typically happen well in advance of the submission though, closer to 9 months out or so. I do not think Amarin had a pre-sNDA meeting for R-IT.

The way JT describes the priority review is weird. Basically Amarin will request priority review when they file the sNDA. Maybe he means they’ll simply assume standard review until they hear otherwise? Dunno. Weird choice of words, but we can be sure that the request for priority review is happening at time of filing.

Yeah it’s very strange, and you are absolutely right: these submissions going out within a few weeks of each other would not be surprising or unprecedented. Just the opposite actually. Many companies submit marketing applications to US/EU simultaneously b/c the submission packages are very similar and the markets are so important, so don’t want to waste valuable time like you pointed out.

While strange, I don’t take the silence as anything more than some kind of gamesmanship w/ Amarin playing things close to the vest. We’ll see the EU submission filed sometime in 2Q IMO.

Nice find, thanks for sharing. I noticed this:

““sNDA to seek expanded label for cardiovascular risk reduction”

Is this the first time they’ve explicitly stated what would be on the label? Obviously not a surprise, but I don’t think they’ve specifically mentioned this previously. The proposed label goes in the sNDA, so it makes sense they’d know the exact labeling language by now.

Yep, EU is a huge market and definitely next on the priority list. If the drug is approved by FDA in US, there’s a very good chance it’ll be approved by EMA as well. Many times the US/EU submissions are dispatched in parallel, or very close to one another.

They are definitely being coy regarding the EU filing, but they know what we do. There’s nothing stopping them from submitting the EU marketing application very shortly after US submission. They can figure out the partner/commercialization piece after that.

CC, I think you hit it on the head. Such a large amount of patients is definitely contributing to the size of the dossier, when you consider case report forms and patient data listings are included for every individual patient. Then you throw in massive clinical study reports and other huge documents, and it gets quite large very quickly. I’m not sure what the average page count is, but it’s a good question. In the past, I’ve always looked at it from perspective of amount of files in the submission. But either way, this is a big submission and that’s probably part of the reason it’s gonna take them ~6 months from topline to sNDA filing.

It’s a good question sts, and the way Amarin has described the process is a bit confusing.

Basically it boils down to this: sNDA gets submitted, and in parallel w/ submission, Amarin also requests a priority review. This starts the review clock...

From there, FDA has 60 days to notify Amarin if we received priority review. If yes, and assume we are notified on Day 60, we’d then have (at most) 4 more months for FDA decision on the sNDA, for a total of 6 months, max review time. Could have a decision even sooner, potentially.

If we don’t get priority review, and assume we learn this on Day 60, we’d then have (at most) 8 more months for FDA decision, for a total of 10 months, max review time from sNDA submission. Again, could be sooner, this represents worst case scenario.

Hope this helps. I think we get priority review for sure. We will learn soon enough!

There is definitely no reason, at least operationally, that this EU submission can’t go in very quickly. But Amarin is playing things close to the vest here, for some reason. I contacted IR recently and stated the same, regarding timing, but they said they wouldn’t be providing any time frame on EU submission, at least for now. I agree this silence on the topic could be related to implications for potential partners. Also, most investors don’t realize that these (US/EU) submissions are basically clones of one another, w/ a few regional differences.

Once a firm EU submission date is announced, I think it will be a pleasant surprise to many.

BB,

They do actually, though in my experience it’s been more difficult to obtain accelerated review in EU than in US.

Regarding timing of EU Marketing Authorization Application (MAA)... this should go out no later than end of 2Q. Not sure why Amarin is saying end of year, that would be a colossal failure if it took them 9 months from US filing. Many times US and EU submissions are submitted simultaneously. I have worked on several that went within weeks of one another. 3 months would be the max time they would need to get it prepped and submitted. Again, this is because US/EU share a harmonized dossier format, so lots of content reuse going on.

I feel this (timing of EU submission) is flying under the radar, but mark my words: end of 2Q at latest :)

Every dossier (eg NDA, sNDA, etc) is submitted electronically with an XML based “TOC”. The reviewers use that to navigate the different portions of the submission. Clinical, non clinical, manufacturing, etc.

Much better than thumbing thru 20k pages of binders like the old days :)

FDA has been mandating electronic submissions for a long time, well over 10 years. Makes it much easier for the reviewer and sponsor alike. If Amarin tried to submit this sNDA in paper format, it’d be rejected.

If sNDA is submitted by end of 1Q, they should have the EU MAA filed no later than end of 2Q, if not sooner.

Of course they’re gonna assume standard review, regardless of how confident they are in getting accelerated review. It’d be foolish and irresponsible to do anything otherwise.

My thoughts too re: sNDA announcement. End of Feb was my best estimate, that would’ve given them 5 months from topline results to submission.

Let’s see what happens!

I think the guy on that list out of Andover, MA is related to BS. Both are based out of Andover as well. Maybe just a coincidence?

Either way, good find.

I agree regarding timing of EU submission. I reached out to IR recently asking about that submission date, and they said they weren’t able to share any info. So they’re playing it close to the vest there.

But as we’ve discussed, simultaneous (ie within a couple weeks of one another) US/EU filings is very possible w/ marketing applications and is often part of a company’s regulatory strategy. The submission requirements/dossier format is largely harmonized across US/EU, and that’s why it’s feasible operationally. Yes, one application is a supplemental one (US sNDA), and the other is an initial application (EU MAA), but the MAA can leverage documents from both the R-IT sNDA, and info (eg previously submitted manufacturing details) from other V applications, eg MARINE. It’s all about content reuse and harmonized standards across regions.

I don’t see any reason Amarin would deviate from this approach, it would make no sense. So I expect MAA submission within ~2 months of sNDA submission. Anything else would be disappointing to me, just based on previous experiences.

US and EU are closely harmonized in terms of their requirements, so no additional study is needed in EU. China is different though. In addition to R-IT, Amarin needs a China specific study to show the drug is safe and effective in Chinese population. I assume this is the study that began in Jan 2018.

After that study concludes, Amarin will submit both R-IT and China specific study in their China NDA for V.

FDA would inform Amarin of being granted Priority Review no later than 60 days post submission. So if we submit sNDA in Feb, which I think is the plan, we’d know for sure sometime in April.

Amarin may have a hunch prior to those 60 days, depending on how closely they’ve been interacting w/ FDA prior/during this period. But nothing is guaranteed until day 60.

I believe we’ll receive it, as I know others do too.

Agreed. He is taking a conservative approach (standard review) in his projections, which is the responsible thing to do, no matter how optimistic he might be on receiving an accelerated review from FDA.

Yeah, besides script uptake, I'm not sure we have any major catalysts until the sNDA goes in. Unless we hear news of an EU partner in the meantime. But the sNDA filing will be a nice one, and potentially receiving Priority Review 2 months later would be another good one.

If we think about JT's assumptions of sNDA sometime in 1Q 2019, and standard review (10 month timeline), and projected approval by end of 2019, I think he is tipping his hand that the planned sNDA submission date is in February or earlier.

If it were in March, and we received standard review, that would project to an approval in January of 2020...

You’ve got it right isaeed. The US/EU submissions can go in parallel, which typically means within weeks of one another.

It seems they are debating whether to bring in an EU partner now, or after the MAA is submitted. The partner is needed mainly for commercialization purposes, so they have that flexibility.

Yup, a potential approval by June sure would be something.

Sadly, I am still thinking that was a mistake by JT re: sNDA timeline. Sounds like you and BB have queries out to IR, so I'm sure we'll get clarification on the topic very soon; they seem to be quite responsive.

Nice catch there, I did not pick up on that previously. Yes, I would now say CP is the likely route, based on that first quote you shared.

I have heard JT speak optimistically of receiving priority review in US, but don't recall hearing him comment on the same topic in EU, but I may have just missed it. I will see what I can dig up. That would be awesome to get it in both US and EU.

Thanks north. I would agree we'll get priority review in US, and hopefully something even quicker than the 6 month window.

I did not see the news regarding Losartan, but that is interesting to hear, I will def take a look there.

G, good question regarding the procedure type. I know there are certain instances where it’s required to file CP, but don’t believe that applies in Amarin’s case w/ V. So it could be CP, MRP, or DCP. I don’t have a good sense at the moment which route they’ll go, but yes, CP is certainly a possibility.

Regarding accelerated review, that is much more difficult to receive in EU, so much less optimistic there, as opposed to US, where I think we will receive it. I heard a recent instance where a company had a drug receive breakthrough designation, but still didn’t qualify for expedited review in EU. Yikes.

Yes, good catch BB; I picked up on that today as well. I am pretty sure he misspoke, and really meant by end of 1Q, as an sNDA submission by end of 2018 seems highly unlikely, if not impossible. I would love to be wrong, but just the way I see it.

Upcoming Regulatory milestones

During the call today, JT was asked a question about upcoming milestones, so I thought it made sense to chart out the upcoming regulatory ones, some of which he mentioned today. I am currently assuming February 2019 sNDA submission, but could be later, hopefully no later than March though.

These numbers, specifically the review times in US, are different than my original projections, they are shortened by 2 months. If filing an Initial NDA (not the case here), that adds 2 months to review time, for both priority, and standard review.

February 2019 (just a guess, but this is achievable in my mind) - sNDA submission to FDA

April 2019 – Notification of 6M Priority Review (FDA must inform sponsor after 60 days if granted Priority Review)

August 2019 (if granted Priority Review) – FDA sNDA Decision – Approval hopefully!

December 2019 (if Standard Review) – FDA sNDA Decision

And of course we can hope that the Initial MAA is filed in EU around the same time as the US sNDA. Approval of that would be projected ~ 1 yr from filing, so some time in 1Q 2020. In the call today, JT reiterated what I said in an earlier post; that is that the EU submission can be largely created off the “baseline” US dossier.

Hi G,

It's a really good question, and something I have wondered about myself. I wasn't sure if maybe I was just missing something, being new to the company and not knowing the whole history.

My only guess at the moment is that it is probably due to commercialization reasons, and also maybe lack of a partner to facilitate that. But still, it is odd to me.

I inferred Elisabeth's response to mean Amarin will:

a) Find an EU partner now, to help them execute on the EU MAA submission activities, and subsequent commercialization effort

or

b) Begin work on their own on the EU MAA submission, and find a partner later, to support the commercialization effort

IMO a partner w/ a global footprint is a must for the commercialization piece, but again, that could come later in the process...

No doubt about it. US and EU is where the $$ is at. Fingers crossed!

Thanks BB, it's exciting to know that parallel filings are at least being considered at this time!

I would assume (but not 100% sure) all revenue projections are currently for US only. But if Initial MAA is filed around same time as sNDA, the EMA decision would be within a year from the filing.

Hi marzan,

Unfortunately I have not had a chance yet, but will try to take a look at it tomorrow or over the weekend. My focus today was on interacting with Amarin IR to assess their thoughts on feasibility of parallel US/EU submissions :) Sounds like there is some potential there, which is exciting.

I will def take a look at the Anchor materials soon though, this is good stuff for me to understand better on my own end as well.

Thanks Kiwi, I've provided my feedback in my previous post. It's a good point isaeed raised, i.e. that sNDA is for expanded label in US, whereas application in EU will be an initial filing in that region.

It's a very good point re: sNDA (US) vs Initial MAA (EU)

But that said, it all comes down to content reuse across the two dossiers.

For the sNDA, certain information wouldn't necessarily need to be included, e.g. previously submitted nonclinical studies, manufacturing information, etc, that would indeed need to go into the Initial MAA, as that information obviously wouldn't been filed previously in an EU marketing application.

For sNDA, Amarin would just cross reference their US applications for which that information has previously been submitted, while submitting the relevant new clinical information in the new sNDA.

For Initial MAA, Amarin can reuse submission components created for their new sNDA, as well as those documents being cross referenced within the sNDA from their other previously filed applications.

The key enabler for content reuse is the common submission format for both US and EU submission components. It is harmonized to an ICH standard called Common Technical Document (CTD), or eCTD, which is the electronic presentation of these dossiers. eCTD is a requirement for submissions in both US and EU (and other ICH regions).

I hope this helps and did not put you to sleep :)

Thanks D, I appreciate that very much. And likewise, I enjoy getting your perspective as well, both here and on ST.

Hi mangoman18,

Apologies for the delay in my response and thanks for the nice welcome! And yes it is a reference to that; kind of silly, but just went with it :)

As for your question: I need to take a closer look, but I would suspect sNDA preparation was happening far in advance of this. The typical trigger, i.e. when the rubber hits the road for submission prep, is when database lock happens for pivotal study, w/ topline results happening shortly thereafter. Industry standard is 6 months from that time (i.e DBL of pivotal), to regulatory submission, but it can be done quicker. 4 months is the quickest I have heard of it being done, but I'm guessing others may have pulled it off faster.

Agreed :) This means means simultaneous filings is, at a minimum, being considered.

Hi north40000,

In cases of Oncology, especially when breakthrough designation is given, it can be much quicker. Maybe half that time, so 3 months instead of 6. This was the case with Opdivo. Not so common outside the Oncology space though.

You are correct, approval would never happen within a few days of submission. It would be at a minimum, a few months.

Hope this helps.

Vascepa marketing applications for US and EU

Just fired this off to IR. IR response is below original e-mail.

Dear Elisabeth,

I had a question I was hoping you could provide some insight into, regarding Vascepa marketing applications in US and EU.

I know much of the focus is on the US sNDA, but has Amarin considered doing simultaneous marketing applications (i.e within weeks of one another) to both FDA and EMA?

This is common practice for many sponsors, as much of the EU MAA dossier can be re-purposed or "cloned" from the US dossier, which lowers the operational burden. The US dossier tends to be more rigorous to build, as FDA requires full case report forms (CRFs) and datasets, whereas EMA does not require this for MAA.

It would be great to hear if Amarin is considering this as part of their regulatory strategy. Many thanks for any color you can provide in regards to this.

Regards,
Eric

-----------------------------

Hi Eric- You clearly know much about this process.



We are determining now if we want to start the European process with a partner, or file first then partner. There is not much other information I can provide at the moment.



Thank you for sharing your knowledge.



Elisabeth

Hi couldbebetter,

Thanks for the kind words. I am enjoying the dialogue w/ yourself and others as well. Agree, it's much more pleasant when folks are cordial; regardless if we agree or disagree w/ one another.

Based on the recent offering, and just everything I've read, it does seem Amarin intends to GIA in the US, at least for the next year or so, which would take us through submission and FDA (and who knows, maybe EU?) approval. I think Amarin is confident they'll get approval and expanded label, where maybe potential BO partners are not as confident in this, and maybe that's leading to some lowball offers. Who knows for sure, this is all just highly speculative.

I think it's either that, or some gamesmanship on Amarin's part to telegraph GIA in US as their intention through the raise, and negotiate from a bit more of position of strength for a BO in short-term. I would bet on the former, and that they will GIA in US for the next year. I still see a partnership in EU as highly probable, and would make perfect sense. We'll see!