Koo: "Bear so what exactly can we expact the design paper to state? Would that not delay the Topline news release that much further?"

Koo, take a look at some example rationale and design papers for REDUCE-IT, CANTOS, FOURIER and ODYSSEY. There are others, but those should give you a good idea of what to expect. I have no idea what you mean by implying that a BETonMACE rationale and design publication would delay top-line data release. Please explain.

Narmac: "I assume the RRR data for the top line results is the tally of both the lipitor and the crestor legs of the trial,,,,,,,,,just musing here that the crestor side of the leg might be awesome while the lipitor side might be anemic"

Narmac, from my understanding the two statin groups are combined for the main primary outcome analysis. However, the lipitor vs. crestor is a pre-specified comparison so they will also report out %RRR by statin type. There is evidence to suggest that apabetalone works better with crestor vs. lipitor for plaque reduction (see this news release and this patent). Figure 6 in the patent also shows some data on cumulative MACE rate for crestor vs. lipitor and it appears both statins showed some benefit on MACE. Maybe better with crestor but hard to tell. But what happens if BETonMACE fails to show significant MACE reduction for the combined statin group, but does show robust and significant MACE reduction in the crestor group (presuming little to no benefit in lipitor group)? Would success in a pre-specified crestor subgroup, but no success in the combined statin group, be supportive of a NDA/MAA application and likelihood of FDA/EMA approval? Tough to say. Hopefully this won't be an issue and the primary outcome will be met with significance with the combined statin group.

Fenix: "I understand the pooled data for the phase two trials in aggregrate was highly significant for Mace reduction, in this group of subjects and the number of such subjects were small in each individual phase two trial but does anyone know if someone calculated the p values in each individual trial for this group of patients and what were the results. TIA"

Fenix, I don't recall Resverlogix ever revealing MACE data for ASSERT trial alone or SUSTAIN trial alone, so I can't help you with p-values there. For ASSURE alone, Resverlogix noted in this news release of a trend (not sure of p-value) for MACE reduction but never provided any details that I'm aware of. Regardless of whether or not the individual trial MACE analyses achieved a significant p-value, keep in mind that these trials were never designed/powered to be cardiovascular outcomes trials, these comparisons are based on a small number of MACE observations, and very few of these MACE observations were 3-point MACE. I've broken this down before in this post.

BearDownAZ