Replies to post #197875 on Amarin Corp Plc (AMRN)

[HDGabor]

M-

You may be helped by reviewing the 21st Century Review Process Desk Reference Guide

Looks like you did not realize I quoted from / cited it in my posts … 21st Century Review Process Desk Reference Guide

We recommend you find a consultant that has served in regulatory affairs, perhaps as a representative liaison (as our member has)

Better to replace her / him ASAP …

We reassert, the Filing Communication (day-74 letter) is always sent to the applicant regardless of whether or not the application is given Priority Review (P) or Standard Review (S).

No disagreement … I did not say differently. Agree.

The "Priority Review Determination" letter due on or by day 60 referenced by you in guidance documents for industry does not preclude the "day-74 letter," also known as the "Filing Communication." … The Filing Communication, which is always sent on day 74 of the review.

The guide says, you wrote, I agree:

For a Priority Review, the RPM prepares one of the following three communication types:
1. If there are filing issues but they are not ready to send to applicant by day-60, send the “Priority Review Determination” letter by day60 then send the “Filing Issues Identified” Letter by day-74.
2. If there are filing issues and they are ready to send to the applicant by day-60, send the “Filing Issues Identified” letter by day-60.
3. If there are no filing issues, send the “No Filing Issues Identified” letter to the applicant by day-60.

however your view is that additional 3 types exist:
4.: 1. + “Filing Communication” by day-74.
5.: 1. + “Filing Communication” by day-74.
6.: 1. + “Filing Communication” by day-74.

But these versions / scenario do not exist …

The Filing Communication ("FC") contains (as you wrote):
-the planned timeline for review activities, including, at a minimum the target dates for transmitting initial labeling and PMR/PMC comments;
-the planned date for the internal mid-cycle review meeting;
-preliminary plans on whether to hold an Advisory Committee (AC) meeting to discuss the application; if no plans, they will advise they are not currently planning to hold an AC meeting
AND
- review designation ("The RPM notifies the applicant of a priority review designation in writing by day-60, or of a standard review by day-74 (in the Filing Communication).")
- any review issues identified to this point ("The filing communication gives the applicant early notice of any review issues identified to this point")

The FC is due by day 74 in case of Standard Review and by day 60 in case of Priority Review (as the “Filing Issues Identified” Letter could be sent by day74; see point 1. above).

I see your mistake / misunderstanding: you think that the “Priority Review Determination” and / or the "Filing Issues Identified” / " “No Filing Issues Identified” are not part of the FC in case of Priority Review … but they are. (The FC got the aka name - "day-74" letter - based on the standard review due date …)

As an investor if you are concerned of an AC you really cannot let down your guard, as surprise announcement could also occur (though admittedly is rare). With the Vascepa efficacy supplement that could potentially occur into August.

I do not have any concern regarding the AdCom, since other than a review issue identified later (it is a possibility but not likely) the FDA does not plan to hold an AC.

You may be helped by reviewing again the 21st Century Review Process Desk Reference Guide; page 21; Filing Communication section. It is B&W ...

Best,
G

[MedResCollab]

On an Advisory Committee (AC) Meeting & Clinical Hold

Previously we stated that applicants are told of preliminary plans to hold an AC meeting before or in the day-74 letter, also called the “Filing Communication,” and asserted that the day-74 letter is always sent, and is always sent on or around day 74 of the review—all of which is accurate for apps in the PDUFA V and VI programs (i.e. forget the 55 day rule from 2008). We also stated that it is by the day-74 letter (and especially for Priority Review applications) that applicants are told if there are “no current plans” to hold an AC meeting, which is also accurate.

However, at a recent conference (June 25) the CEO disclosed that they have heard nothing at all on the topic from FDA yet. June 25th is too far from the goal date of the day-74 letter for them not to have received it. The only explanation for the disparity then is that it is currently a matter of internal dialogue/review, and they are weighing whether or not to conduct one, and have decided to wait until the mid-cycle review meeting to decide, and thereafter notify the sponsor. To us that conveys a deliberate dive into the data to find if there are grounds to hold one or not, in particular as concerns whether or not cardiac medications were hindered in placebo group. We think the silence also means they are at the same time seriously considering placing a clinical hold on the EVAPORATE trial (and possibly icosapent ethyl IND), and may find it legally problematic to say anything to the sponsor before their investigations are more mature.

It is possible that our research has prompted the agency to look deeper at issues we brought to their attention, recommending in our conclusion that they consider (among other things) placing a clinical hold on EVAPORATE, as its placebo group subjects may be exposed to immediate and serious harm. Or, it could have nothing to do with our research at all.

A clinical hold on Evaporate remains a possibility, and could be announced at any time. And it seems likely that FDA will convey a resolute decision on whether or not to hold an AC meeting to the sponsor within two weeks after holding the mid-cycle review. Or, as we’ve also stated previously, most probably by July 10th, though somewhat later is of course also possible.

Regards,
-MRC