Thanks for sharing that article "Chemical probes targeting epigenetic proteins: Applications beyond oncology" in your recent post Imtesty. It was a nice review on potential applicaiton of epigenetic drugs, including BET inhibitors, on inflammation, viral, metabolic and neurodegenerative diseases. For inflammation, the review had a big focus on NF-kB, which BKC has previously brought to our attention as a key mechanism of the anti-inflammatory actions of BET inhibitors and BKC has also given us a great review of BET inhibition in a disease context (see links at end of message for BKC's awesome SA articles).

I'd like to highlight a few sentences at the end of that review that Imtesty linked to:

"Given the biologic functions of these epigenetic modulators in normal biology, ranging from embryonic development, cell differentiation processes to memory formation and other functions in the brain, it is however currently not clear if inhibitors against these targets will be suitable for long-term systemic treatment of inflammatory diseases and the development of specific drug targeting systems may be necessary for safety in therapeutic areas outside oncology."

The longest patient on drug in BETonMACE will reach 21 months on drug on August 11, 2017. We've had 4 DSMB reports come out with no safety concerns. According to current BETonMACE protocol, patients are dosed for up to 104 weeks followed by a 4-16 week safety follow up. So the first patient(s) will reach their 104 week (2 year) treatment endpont in the Fall on November 11, 2017. The window for any "surprises" in terms of unexpected side effects/adverse events is rapidly closing. As more and more patients get to the 2 year dosing milestone, the confidence grows stronger and stronger that apabetalone is safe for long-term use. 

Back to BKC and Seeking Alpha.......I had another look at his SA articles on Friday afternoon (links to his 3 most recent articles below). I suggest you all do so as well. A great reminder about the impressive post-hoc analyses for MACE reduction in terms of observed MACE event rates (5-point MACE), RRR and p-values, and more importantly, a reminder of the strength of BETonMACE vs. the post-hoc analyses in terms of # of patients, length of dosing, and optimal patient population.

BETonMACE (at least 2400 patients) will have ~5 times the number of patients that were included in the largest MACE post-hoc analysis (ASSURE+SUSTAIN, diabetic and non-diabetic patients, 499 patients), plus there will be equivalent numbers of placebo and apabetalone treated patients (there were ~twice as many apabetalone patients vs. placebo patients in the SUSTAIN/ASSURE post-hoc). This equal distribution of patients should improve the stats in BETonMACE. Compared to the diabetes-only post-hoc of SUSTAIN/ASSURE (based on ~200 patients: 65 placebo/127 apabetalone), BETonMACE will have ~12 times the number of patients since ONLY diabetic patients are being enrolled. Plus all patients must be low-HDL for BETonMACE, which wasn't the case for ASSURE/SUSTAIN. ASSURE/SUSTAIN were only 6 months long.....BETonMACE is 24 months long. 

Looking at those tables in BKC's articles that summarize the post-hoc analyses, I have renewed excitement that the BETonMACE futility analysis will pass with flying colors. And I am starting to feel that a 30% RRR in MACE in BETonMACE should easily be achieved and I wouldn't be surprised if 50% RRR was achieved. Of course, I may just be high on the Kool-Aid right now, so all of this is just my opinion and do your own due diligence, yadda yadda yadda.

Resverlogix: Analysis Of The Science Behind RVX-208

Resverlogix: RVX-208 And The Epigenetics Of Age-Related Diseases

Resverlogix: The Science Is Getting 'BETter' For RVX208

Have a great weekend everyone, especially those up north with your long weekend/Monday Civic Holiday.

Best regards,

BearDownAZ