rthur re "Your overriding point has always been about liver fat.


And I've said the same thing about it consistently since new agents arrived on the scene and stand by those assertions. It won't be a problem for HoFH though it it likely will compete with lomitapide there if it also gets approved. It's not a big problem for severe HeFH but if PCSK9 inhibitors continue to do well they will encroach somewhat there.

This isn't some far out conjecture by me about severe HeFH. The answer that it's somewhat of a problem is in and the FDA said essentially the concern about safety required this entire year long additional Focus FH trial before considering approval for severe HeFH.

That is all about liver fat. Efficacy has never been an issue. Elevated ALT's without Hy's Law would be a concern, just not a big deal, you monitor them and if you have to make changes you do. Injection site reactions and flu-like symptoms are mainly nuisances at this point and not something the FDA would make a big deal about. But they refused to even accept severe HeFH to be considered in the first filing and unless someone has another explanation I think the main concern is liver fat.

It is liver fat that makes mipo not very competitive beyond severe HeFH but especially beyond general HeFH. Here is where PCSK9 inhibitors if they make it to market render mipo irrelevant because they have no liver issues. They also have no muscle issues so they would be the ideal combos with statins we once thought mipo might be. Liver fat with mipo and the fact they're going to pour massive amounts of money into their PCSK9 drug is why Sanofi will not do a rather difficult expensive outcomes trial for mipo which based on what the FDA has determined eliminates mipo as a possibility beyond severe HeFH in the US.

So what is it in what you read that disagrees with that? I'm saying over and over again these must be viewed in terms of the context of particular patient groups. For HoFH liver fat OK. For severe HeFH not OK but probably will be acceptable and allow use in a portion of this fairly small group. Beyond severe HeFH liver fat is a problem and if the PCSK9 inhibitors are around with their current profile they render mipo largely dead beyond HeFH.