Regarding Alnylam's RNA interference approach to dereasing levels of liver PCSK9, Golfyeti wrote "Do you have an opinon on the potential for ultimate success for RNA interference?  I mean beyond what you pointed out about its less frequent injections and lower-than psk9 cost?  Have they shown improved MACE outcomes, not just lower ldl levels?"

Antisense technologies, including RNA interference (RNAi), have already shown great promise and some have already made it to market. A great summary of different antisense technologies can be found on the webpage of Ionis Pharmaceuticals (formerly ISIS Pharmaceuticals......what bad luck in that name huh?). So in general, I think the antisense/RNA interference drug pipelines will continue to give rise to successful drugs for various indications. 

Specifially for inclisiran, there has not yet been a cardiovascular outcomes/MACE study. They are starting that soon and the results will be years away. It is likely that Alnylam will seek approval for LDL-lowering for inclisiran first while the cardio outcomes study finishes. Very analagous to the position that Esperion is in with ETC-1002 right now. Assuming that inclisiran is shown to be effective in Phase 3 and can be dosed less frequently that Amgen's Repatha, and also assuming that the price point of inclisiran is cheaper than Repatha, then I can see the RNAi-mediated inclisiran becoming a preferred option over the monoclonal antibody-mediated Repatha for PCSK9 inhbition-mediated LDL-lowering.

Perhaps there will be an antisense/RNAi drug targeting one of the BET bromodomain proteins such as BRD4 someday? This strategy would not be able to achieve the bromdomain-2 selective inhibition of apabetalone, but for certain indications this approach may be possible. It is my understanding that antisense/RNAi doesn't achieve a broad tissue distribution, so there may be disadvantages there. Easy to get it to liver, but for organs like brain not so easy (unless one uses Transcendpep.....biOasis plug).

BearDownAZ