Cabel,

You wanted Tundup or I to clarify this statement from Tundup's June post:

"I recently had the opportunity to catch up with management. Apparently the blinded data is all pointing in the right direction. The rate of MACE events has been dropping steadily since the beginning of the trial, starting off at the expected 8% per 100 patient years but now down to 7.2% per 100 patient years (originally expected to see 10%-11% MACE event rate)."

Specifically, Cabel asked "Are you saying that the company anticipated a MACE event rate of 10%-11% in June,... ?"

In my opinion, I think there was a misunderstaning and/or breakdown in communication between Tundup and whoever Tundup talked to in Resverlogix management. As stated in my post yesterday, BETonMACE was in part modeled after the EXAMINE trial. In EXAMINE, the median drug exposure was 1.46 years,  or ~18 months. At this time point of ~18 months, the observed 3-point MACE event rates were 11.3% and 11.8% for the aligoliptin and placebo groups, respectively. Another way to express event rates is as events per 100 patient years, which can also be referred to as an annual event rate. To get this, take the event rates at the median drug exposure time point (11.8% and 11.3%) and divide by 1.46 years to get 8.08 and 7.73 events per 100 patient years, or annual event rates of 8.08% and 7.73%.

BETonMACE was originally designed to have an average drug exposure of 18 months similar to EXAMINE. Therefore, the projected 10-11% event rate numbers for BETonMACE refer to the projected event rate at median drug exposure of ~18 months. The 7 to 8 per 100 patient years, or 7% to 8% annual event rate, which is based on a 12 month period. Based on EXAMINE, most diabetic patients with a recent ACS are most likely to have a subsequent 3-point MACE event during the first 6 months of the follow up, and then the rate drops a bit in each of the subsequent 6 month periods. BETonMACE was nearly 90% enrolled by the end of 2017 and also BETonMACE protocol was amended to allow for all patients to continue dosing past 104 weeks. Taking both of these factors into account, combined with the likeliehood for 3-point MACE event to most likely occur during first 6 months of follow up, means that it is totally reasonable to expect the 8 events per 100 patient year event rate reported ~February 2018 to drop to ~7.2 events per 100 patient years a few months later.  

In Cabel's other post, he/she asked "My question is: Even if low HLD has no effect on the MACE event rate,.. if we go from 11% down to 7.2% (as of tundup's post back in June 2018),.. is that not a positive indication that our drug is working,...?  Would it not give us a RRR = 34%,..?"

I think this is pretty much covered in my first response above. There was confusion about event rate at median drug exposure and event rate per 100 patient years (aka annual event rate). Because of all of the uncertainties about the placebo event rate in BETonMACE, how the low-HDL may affect placebo event rate, what kind of %RRR apabetalone will elicit, and whether there may be synergy between apabetalone and rosuvastatin relative to apabetalone and atorvastatin, one cannot conclude anything from an average event rate that includes all patients, in my opinion. Too many unknowns. Perhaps both placebo and apabetalone groups have event rates of 7.2%, leading to an average of 7.2%. Or perhaps the split between placebo vs. apabetalone is 7.7% vs. 6.7%, or 8.2% vs. 6.2%, or 8.7% vs. 5.7%. They all lead to the same average of 7.2%. As I stated in my other post "One can't assume that BETonMACE placebo patients will have this exact same event rate as EXAMINE placebo patients. In addition to the low-HDL variable, standard of care changes over time and no two trials are going to have exactly the same event rate even if they are in similar patient populations run at about the same time." One could definitely paint a rosy picture by cherry picking lots of variables, but the truth is there is too much uncertainty in these variables and there are many possible outcomes (some good, some bad). 

Lastly, Topcoin stated "So with half the on drug group also taking Crestor will the on drug event rate drop even further versus placebo group to help yield good results ? What was Crestor combo 208 5 point RRR ; something like 75% and both Crestor plus all other statins group 50% or so ? Will Crestor combo with 208 really help significantly ? Doesnt previous data suggest it ? I probably am missing something here ?"

I think the only resource that I've seen that breaks down the rosuvastatin vs. atorvastatin MACE event rates (and also by HDL level) is in Fig 6 and Fig 7 of the patent "COMPOSITIONS AND THERAPEUTIC METHODS FOR ACCELERATED PLAQUE REGRESSION." See link below. Keep in mind that this is 5-point MACE data and not 3-point MACE data, that there were very few 3-point MACE events in the post-hoc analysis of SUSTAIN/ASSURE, and these patent graphs show diabetic and non-diabetic patients, whereas BETonMACE only has diabetics. There may be some hints that the rosuvastatin and apabetalone works better to reduce MACE than atorvastatin and apabetalone; however, there is not enough data to conclude this unequivocally, in my opinion. Surely, for plaque reduction rosuvastatin and apabetalone worked better than atorvastatin and apabetalone. But the beneficial effects of apabetalone extend beyond just plaque reduction. So the jury is still out as to whether there will be a difference between the two statin types on 3-point MACE readout.