Iconoclast,

Yes, BETonMACE is getting close to the finish line and Resverlogix appears to be funded to get there. That's great! If apabetalone does what we hope, long gone will be the days of haggling about a price range of $3 to $4. A few comments on your previous post:

Patient years: As we've discussed recently on this board, there is uncertainty as to the current number of accumulated patient years and whether or not there is any minimum patient year requirement to finish the trial and appease the FDA. So I have healthy skepticism with anyone's statement of current patient years and its implications if it doesn't come directly from Resverlogix. 

DSMB and safety: We are about to undergo the 8th DSMB review; the 7th already occurred. Although passing 7 previous DSMB's is a good sign, remember that Resverlogix is in unchartered territory with the apabetalone dosing period. Previous trials did not dose past 6 months. Some patients in BETonMACE have been dosing 3 years and counting. Apabetalone is a first in class bromodomain-2 selective BET inhibitor. As far as I know, no other current or past clinical trial has dosed any patients with any BET inhibitor (pan or selective) for this long. There is still a chance that adverse events/toxicity issues may arise with chronic dosing. However, with BETonMACE getting close to hitting 250 events and the dosing period ending, potentially by year end, I agree that it is unlikely that anything new will arise in the 8th DSMB report. 

One must also keep in mind that a comprehensive reporting of adverse events won't be seen until full data presentation/publication. There are certain signals (i.e. liver transaminases) that will be of particular interest to those who have followed apabetalone/RVX-208 in the past. Even if the DSMB hasn't flagged anything, there could still be increased incidence of certain adverse events with apabetalone that are notable in the full data and may cause investor concern and/or difficulties with NDA/MMA filings with FDA/EMA.

Efficacy: BETonMACE is closing in on the originally planned goal of 3600 patient years and 250 3-point MACE events. However, closing in on patient year or event # goals gives no indication of drug efficacy. The argument against the "longer the better" viewpoint is that BETonMACE has taken so long (beyond 36 months) primarily because of prolonged recruitment time to reach ~2400 patients, not because the trial has exceeded the originally anticipated ~3600 patient years. 

Many trials have gone to completion only to conclude that they did not meet their endpoint with statistical significance. Additionally, BETonMACE is a small CVOT trial with only 250 MACE events. There is some concern that even if apabetalone elicits positive MACE reducing effects, that BETonMACE will not achieve statistical significance for its endpoint(s). Magnitude of %RRR and statistical significance are two different things. There are numerous uncertainties as to placebo event rate in BETonMACE patients and the RRR elicited by apabetalone. I've covered this ad nauseum in the past so I will not do so again here. There are plenty of reasons to expect apabetalone to elicit an impressive %RRR for 3-point MACE, but there are also good reasons to be skeptical of how prior data translates to 3-point MACE reduction.

ELIXA and EXAMINE are the only CVOTs that have attempted MACE reduction in high-risk T2D patients with recent ACS event. Both trials failed and there is some concern that the pre-exisiting cardiovascular disease was so severe/advanced in these patients that drug intervention over the relatively short time period (18-21 months median dosing period) was insufficient to make a dent in risk for recurrent MACE event. Same could be true for BETonMACE patients.

Lastly, I would proceed with caution about assuming efficacy for other indications if it works for one indication. While it would be great if BETonMACE shows effects on diabetes, congnition and renal function, BETonMACE was primarily designed for cardiovascular.  The tissues involved and mechanism of disease are quite different for those different diseases. First things first......nail that MACE endpoint!

BearDownAZ