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
