Awesome post Tada! Just to add onto the conversation about the unique opportunities of BETonMACE....poster LifeGoesOn1973 over on Stockhouse posted:

"excellent point, they jumped from 2$ to 22 $ and their RRR was 25%. RVX is aiming for an RRR of 30% . Their market cap is 6 B, imagine how high our market cap will be when we break their RRR value next week."

I replied:

It is not as simple as comparing %RRR between two cardiovascular outcomes trials.

1) Patient population in BETonMACE is all diabetic; Amarin's REDUCE-IT was not and less than 60% of patient were diabetic.

2) REDUCE-IT had elevated triglyceride requirement; BETonMACE does not.

3) BETonMACE has low-HDL requirement; REDUCE-IT did not.

4) BETonMACE placebo is a standard inert pill; REDUCE-IT used confounding mineral oil that some believe increased risk factors and cardio risk in placebo group.

5) BETonMACE requires recent acute coronary syndrome (ACS) event within 90 days of enrollment; REDUCE-IT did not require recent ACS event. REDUCE-IT had ~30% patients with no prior cardiovascular disease/event (primary prevention). Importantly, no diabetes drug has been proven in clinical trials to reduce MACE incidence in diabetes with recent ACS.

6) BETonMACE has chronic kidney disease patient sub-study looking at change in eGFR and cognitive impaired patient sub-study looking at change in MoCA score. 

7) In Phase 2 ASSURE post-hoc analysis, apabetalone was shown to synergize with rosuvastatin to achieve MUCH more plaque reduction than in patients taking apabetalone and atorvastatin. In BETonMACE, half patients on rosuvastatin, half on atorvastatin. If the synergy for plaque reduction translates to synergy for MACE reduction, then the rosuvastatin sub-group could have MUCH higher %RRR than the combined statin group.

8) Due to the higher baseline risk in the BETonMACE population (all low-HDL, diabetic, recent ACS), any given %RRR will equate to a greater absolute risk reduction in BETonMACE compared to REDUCE-IT, and a more impressive (lower) number needed to treat (NNT) value.

9) %RRR for the 3-point MACE composite is one thing. A breakdown of the individual components (cardio death, non-fatal MI, non-fatal stroke) is another. Reduction in cardio death carries a lot more weight than reductions in stroke and MI. All are good, but reduction in cardio death is key. The SGLT2 inhibitor trial EMPA-REG OUTCOME achieved 14% RRR for 3-point MACE; but it was the ~38% reduction in cardio death that got the standing ovation. 

Tick tock!

BearDownAZ