When I look at the data presented today, two things spring to mind:

1) Chronic kidney disease patients (i.e. low eGFR patients) appear to carry the entire difference between placebo and Apabetalone. Consider this: Overall, there were 149 events in the placebo arm and 125 in the treatment arm - i.e. a difference of 24 events. For the low eGFR subpopulation, there were 35 event in the placebo arm and 13 in the treatment arm, i.e. a difference of 22 events. Thus, the CKD patients account for more or less all of the difference between placebo and Apabetalone. More or less all... More or less ALL of the difference!

2) The other thing is: What on earth happened after 24 months??? Up untill 24 months, there is a stellar performance of Apabetalone, but right after 24 months, the event rate in the treatment arm takes off... Could this have something to do with compliance deteriorating once the patients had been on the originally scheduled 120 weeks (2x52 weeks + 16 weeks follow up) of treatment? We know from the ASSURE study that some patients had no detectable Apabetalone in the blood sample taken at the final visit. Thus, non-compliance is not an unheard of phenomenon. I hope that we at some stage are going to see a so-called per protocol analysis (as opposed to the intent-to-treat analysis) where patient compliance - as judged by presence of Apabetalone in the plasma - is taken into consideration. I am perfectly well aware that it is the intent-to-treat analysis that counts when it comes to regulatory requirements, but the per-protocol analysis is still interesting. Please also note that the question of compliance was raised when the discussant at AHA mentioned the better performance of Apabetalone in the low LDL population relative to the high LDL population.

I have no problem with CKD being the main indication going forward. It is a huge patient poulation with a substantial unmet medical need. Moreover, this patient population is at super high risk of MACE, which could make for a shorter study, since the events would accrue faster than what was the case in the BETonMACE population.

It was also interesting to note that heart failure stood out as a potential indication for RVX208. Heart failure is to a great extent fibrosis driven, and there has been a lot of papers on bet inhibitors having beneficial effects on fibrosis in various organs, including the heart. This would also make for an interesting study, although I think focus should be on CKD.

In my opinion, there is every reason to believe that big pharme will be interested in Apabetalone, but there is in my opinion not much chance of the FDA approving Apabetalone for any indication based on BETonMACE alone. Given the current valuation of Resverlogix, it is probably fair to say that the unlikely chance of having the FDA approve Apabetalone for any indication is already priced in.

GLTA

BKC