Toniv,

I had posted this on Stockhouse last week, but it is also a pertinent response to your question: "My question to scientific posters and others is "what, if any" are the perceived scientific barriers or pitfalls to rvx-208 a.k.a. apabetalone?"

"And just to add to this conversation, RVX-208 aka apabetalone is the most advanced BET bromodomain inhibitor in clinical trials. All of the other BET inhibitors are in Phase I or Phase II. So it is currently unprecedented for the FDA to have approved a BET inhibitor for a Phase III clinical trial. There may be reservations regarding this class of drugs in general.

What RVX-208 has going for it is that it is selective for the second bromodomain, whereas most (if not all) of the other BET inhibitors in trials currently target both the first and second bromodomains. This may be advantageous for RVX-208 by achieving a more selective modulation of the epigenetic machinery relative to a more widespread epigenetic modulation elicited by those that hit both bromodomains. It is also noteworthy that most of these BET inhibitors that hit both bromodomains are in trials for cancer. RVX-208 is the only BET inhibitor in trial for cardiovascular outcomes."

I'm sure there are still a lot of unknowns about long term safety of this new class of epigenetic drug that affects the expression of genes in a variety of biological pathways and in a variety of tissues. The FDA may be more lenient for allowing BET inhibitors for certain cancers, since there may be no other treatment available and the prognosis is already poor for these patients. But for a more chronic condition such as cardiovascular disease, the patients will be expected to take this drug for a much longer period of time. So because of this, the "safety" of RVX-208/apabetalone for CVD may be scrutinized much more than other BET inhibitors for cancer. Very likely the "safety" of RVX-208 for the complement-mediated disorders will be less scrutinized because the prognosis for these disorders is poor as well.

That's all I've got for now from a science perspective. From what I've seen, RVX-208 seems very well suited to be a blockbuster MACE reducing drug for high risk CVD patients. But any first-in-class drug is likely to encounter some pushback to prove its safety.

Best regards,

BearDownAZ