I don’t think it will be announced until the filing acceptance letter on day 60.

That’s correct. If it happens, we’ll learn of it on day 60

Good article. There’s been drastic regulatory reform in China recently. All in the name of making it easier to get drugs to market, and also run clinical trials.

China is actually becoming an attractive market for a lot of companies now.

Good question, I wondered the same myself. But I would say no, it doesn’t have any bearing either way on FDA PR decision.

I have it the same. Day 60 should be calculated from 3/28.

FDA typically acknowledges receipt the same day it’s submitted. And it’s all done electronically, so happens pretty quickly.

I didn’t catch that, that’s good news HLS is targeting an end of April submission. The EU submission should follow shortly after, hopefully by end of May.

Yep. I think that puts sNDA Day 60 around May 27.

Upcoming EU submission deadline is June 3.

Canada submission must be submitted with 2 months of being granted Priority Review, so that will go in around the same time, ie end of May - or earlier.

The 74 day window is accurate, but in the case Priority Review is granted, it will be communicated in the filing acceptance letter at Day 60. There won’t be any Day 74 in that case.

Yes, definitely conceivable Amarin could know of EU Accelerated Approval ahead of the FDA decision on the same (ie Priority Review).

And you’re correct, request for AA and presubmission meetings around the same happen months in advance of the EU submission. But unfortunately we are in the dark on this - and IR is staying mum on it. I have already tried asking everal times :(

Edit: Just realized I didn’t completely answer your entire question. If granted AA in EU, but only standard in US, the expanded label come potentially come in EU first. The regulatory process in EU is a bit more complex than US, so I’d have to look closer at the exact timetable. That said, I don’t think this scenario is likely. I think we have better chance of getting an expedited review in US than EU. It’s typically much more difficult to receive in EU.

Management has been conspicuously quiet about EU plans.

My best guess is they’re getting on their horse to get the EU dossier submitted.

Every time I’ve posted the dates, I’ve pulled from the EMA procedural timetable. Which anyone can look at.
What was previously listed as May 6 date in that document, is showing blank now, so it should be discounted. I presume it was there when I last posted, as it would be weird to randomly make up that date. I don’t follow EU regs too closely, but I don’t think it’s uncommon for some of the review timetables to be amended and changed around.

But it’s a good point- I didn’t realize that it had changed from my last post until you mentioned it. That said, I’m still fine w/ them hitting June 3.

Next EU submission deadline is June 3. Followed by July 1. Marketing applications are different in EU where there are set cutoff dates to submit. So, w/ the most recent submission deadline of April 8 passing, an EU submission tomorrow is the same as a submission on June 2. Either way EMA will not start review of those submissions until the deadline passes.

We can reasonably expect the EU filing to hit the June 3 deadline, w/ July 1 being a worst case scenario. I see no scenario where it would be any later.

IMO Amarin’s assumption of standard review has zero bearing on V receiving priority review (or not).

They are simply stating the most conservative timeline. Which is the responsible thing to do.

I think there’s a very good chance we get PR from FDA. Can’t really think of a reason we wouldn’t...unless something crazy/unexpected happens. It meets all the criteria for an expedited review.

Not sure if this helps, but from regulatory review perspective and speaking globally; it’s Priority Review for US/FDA and Accelerated Assessment for EU/EMA.

But yes, they effectively mean the same thing; it’s a quicker review than standard.

Yup, the US filing is heavily leveraged to create the EU one. And also the Canadian submission, and other countries as well. They all use a harmonized format for marketing applications, which makes things much easier operationally. Can submit in multiple markets very quickly. Often simultaneously.

If they are granted priority review by FDA, it will be communicated in the filing acceptance letter at Day 60.

One other thing to be aware of, is that EU accelerated assesment is notoriously difficult to get. Also, that the company might not announce they received it, until after the submission is received and validated by EMA. Even if they know in advance of the filing. Yes, they are definitely playing things close to the vest in terms of the EU stuff.

I expect the EU marketing application no later than end of 2Q, and could be much sooner.

BB, the request for EU Accelerated Assesment goes in 2-3 months before submission, sometimes earlier. CHMP decision comes about 1.5 months after request for AA.

There are also presubmission meetings w/ EMA 7 or 8 months ahead of submission where AA is discussed as well as the actual submission. These are not required, but are strongly recommended to applicants.

I inquired to IR about the request for AA, and also presubmission meetings, but they couldn’t give me any info there, unfortunately. Was hoping to learn about some of their interactions w/ EMA.

Good question, I was wondering the same. What do the IQVIA/IMS numbers look like? Are they jacked up as well?

Also, just for some context. Many times US/EU marketing applications go within weeks of one another. Basically as simultaneous filings. Again, I think it’s fair to add some extra time, since we’re dealing w/ an sNDA in US vs original MAA in EU...but it’s not going to take that much longer.

I’ve said all along: the early timing of the EU submission is going to surprise many people. At least the uninitiated who don’t read this board :)

What additional information requirements are you referencing? There is actually no requirement for patient data listings/CRFs for EU, which actually makes the EU dossier much simpler compared to US from that perspective.

Yes, US submission is an sNDA, where EU filing is an original application...this is a factor, but the EU filing can simply leverage this previously submitted info from the US applications in the EU dossier. So yes, it’s a consideration, but not a big deal. It’s all about content reuse.

I think your projection of 2 more months is a good one. And it could be much sooner.

That was me. And no, I never commented on speed of transmission. All I said was the act of sending it entails clicking a button. Which is 100% accurate.

These submissions are many GB in size, of course it doesn’t get transmitted in seconds. But I can also tell you it doesn’t typically take days either.

I agree. It’s very bad form to publicly put a target out there to investors, then miss it.

But based on what IR is saying, sounds like they’re still on track for 1Q. Or as speculated elsewhere, perhaps have submitted already and just aren’t saying.

Yeah the process of “submitting” is actually quite simple. Amarin clicks a button, and the submission is electronically submitted to FDA via an electronic gateway.

Has Amarin already clicked the button? Guess we’ll find out soon :)

Thanks for sharing. I don’t know how likely it is, but there’s a chance Amarin may have dispatched the submission already, but is waiting to announce this publicly.

Either way, sounds like they will hit their target of end of 1Q, which is good.

Even so, it’s obviously still (at least to me) a mistake/poorly calculated approval timeline. So I see it more as a sloppy estimate than Amarin tipping their hand of a planned February submission.

I’m a little surprised they’re pushing the envelope as much as they are, considering there’s 4 working days left to submit and hit the 1Q timeline. So maybe this means it’s taking longer than anticipated. It’s hard to say, these are complicated dossiers.

I think the anticipated approval in Dec 2019 was a mistake on JTs part, not guidance on a Feb 2019 submission date. Even if they thought they could hit Feb for sNDA submission, they would never publicly put that out there, especially when they’d already provided the end of 1Q timeline.

You’re right, I was applying original NDA timelines to the sNDA review, which is 2 months shorter.. My bad, got them crossed up.

It still doesn’t change the fact that the sNDA timeline never changed. JT saying anticipated approval in late 2019 was simply a slip up. He should’ve said Jan 2020 as that would’ve represented worst case (most conservative) scenario, assuming a submission by end of 1Q and standard review.

Nothing to see here, move along...

Agreed - I see it the same D. People might be reading between the tea leaves a bit too much here.

Submitting the sNDA ~6 months after topline is a good job by Amarin.

Very good question and it’s value can actually be quantified, when you consider the extra time on the market.

But...typically vouchers are only purchased when a company is not confident in applying for, and receiving priority review up front “the old fashioned way”. This forces the issue and gets them a priority review - at an expense :)

If companies don’t think they’ll receive priority review w/ FDA, they can purchase priority review vouchers from other companies that hold them. They’re a commodity, as they can increase speed to market by several months through reduction of review timeline.

I’m not sure the equivalent exists in EU. But if a company applies for, and receives priority review, there is no kind of excessive fee paid.

Thanks BB, it’d be interesting to learn more there. Elisabeth is great, but she was only able to give me an excerpt from the recent earnings call, where they mention EU submission in 2019.

My big takeaway is the EU/EMA accelerated assesment process starts well in advance of actual submission, and is even sometimes discussed during clinical development, see below:

“Under the PRIME scheme launched in March 2016, it is now possible for applicants to receive confirmation during the clinical development phase that their medicine might potentially be eligible for accelerated assessment.”

Again, I asked IR if Amarin was engaged in PRIME, but they weren’t able to give me an answer there. This is why I think there is a chance they could know already. Either way, they aren’t saying :)

EU accelerated assesment actually gets requested months in advance of submission, whereas w/ sNDA and FDA it goes in parallel w/ the filing.

So depending on submission timing, we might know of a decision on accelerated review in EU, ahead of US. They might even know the decision already. I inquired to IR about this topic (e.g. have they already requested AA in EU, are they engaged in presubmission meetings w/EMA, etc), and they weren’t able to share any details.

Size of dossier won’t have an impact on being granted priority review. It might increase the rigor and duration of review, but the 6/10 month review window (depending on which we get) is plenty of time for them to go thru it.

Individual data listings and case report forms/narratives have to be generated + submitted for every patient/case, which is a huge amount of information (and work!) across those 8000 patients. That is monstrous...majority of Ph3 studies are a few thousand, max.

Very good addition as well, especially w/ all the interest around Europe. Thanks for sharing, this was not on my radar screen!

Thanks sts, I agree w/ pretty much everything you outlined.

Odds of hitting May deadline feel like 50-50 to me as well. Having worked in regulatory submissions I can tell you this (simultaneous US/EU filings) is the norm for a lot of companies. But not knowing Amarin’s operations, it’s possible it slips to the June deadline. But I think the bottom line is this: it’s coming quickly, and probably quicker than most anticipate.

I also agree that most are not aware of these EU submission deadlines, so I thought I would share here. I’m no options expert, but I wonder what calls look like around those May and June dates. I’d expect the stock to pop on news of the EU filing. I don’t see a partner ahead of EU submission either; there is no reason for it. They can get the EU submission out now, then worry about partner later, when they’ll need them for commercialization activities. Partner has next to no impact on getting submission out the door.

On topic of priority review, I think JT described it strangely, not sure why he said what he did. They’ll assume standard review, yes; but that’s just to be responsible/conservative. They’ll request priority review at the same time they submit the sNDA, that is for sure.

Good question. Essentially no, since it is 3/11 and sNDA is not yet submitted. Unless they have something really crazy up their sleeve, probably a long shot :)

EU submission deadlines

In case folks were wondering, EMA is different than FDA in that they’ve got a calendar of strict submission deadlines for marketing applications. Upcoming ones Amarin is looking at for their filing:

May 6
June 3

What this means is that if Amarin were to submit on May 7, one day after current deadline, it would be no different than submitting on June 2, the day before the next deadline. EMA starts their review of all submissions filed by that deadline after it passes. As previously mentioned, I expect them to hit one of these next two deadlines.

After this it would be 7/1, 7/29, and 9/16. But this would be a major operational failure if the MAA bleeds into late July. Hitting 7/1 would be ok, but it can be done much quicker.

Most definitely! Don’t know how I forgot that. Thx for keeping me honest :)