Jkj193741 wrote:"My other question to you was whether the trial results, were positive for 208 and RVX. Do you think they were?"

Yes, I think the results are positive with some caveats. This recently published study conducted at the Baker IDI Heart and Diabetes Institute (Melbourne, Australia) was relatively small (20 patients) and patients were only given RVX-208 for 4-5 weeks. The investigators originally postulated that the RVX-208 induced rise in ApoA-I/HDL-C may impact pancreatic insulin secretion and thereby lower blood glucose (detected using an oral glucose tolerance test aka OGTT). With an OGTT, you give an oral bolus of glucose and then follow the glucose and insulin in the blood over a time course to see the rise and then fall back down to normal. Despite their hypothesis, they did not achieve changes in total apoA-I/HDL-C or observe changes in fasting glucose or fasting insulin. They do, however, document some novel observations on remodeling of HDL size and changes of certain HDL lipid classes during this 4-5 week treatment period. In my opinion, the OGTT differences between the groups are minor. However, because they used some stable isotope glucose tracers, they were able to document which aspects of glucose metabolism were effected and responsible for those minor changes during the OGTT. From the conclusions, "RVX-208 delayed and reduced oral glucose absorption and endogenous glucose production, with plasma glucose maintained via reduced peripheral glucose disposal." Importantly, keep in mind that from the post-hoc analysis of the ASSURE/SUSTAIN trial "the time required for RVX-208 to reduce blood glucose was not observed until at least 12 weeks following initiation of treatment." So although this Austrailian study made some interesting observations that can serve as good bio-markers/endpoints for future studies, I think the study was too short to definitively conclude too much.

Jkj193741 wrote: "In reading the article in bio business which you kindly called to our attention, unless I interpreted the comment of DM in the wrong way, he says RVX is not interested in FDA approval,mas they only want glucose reduction and not MACE reduction. I know this is run on post but DM is quoted as saying, more or less, that RVX is only interested in whether the payors like 208 not the FDA. maybe he was quoted in error or I missed his intent. It would seem to this reader that the new published report is just what the FDA may be looking for. Please correct me if I am in error."

The last two paragraphs of the article read:

"The most important target for a drug company is not so much the FDA or Health Canada approval, it is securing the approval of payer groups, McCaffrey says. That means having the support of government bodies in Canada, and insurance companies and health care groups in the U.S.

"If a drug is approved by the FDA and payer groups just don't believe in it, or it costs too much, the payer group is not going to do anything," McCaffrey says. "It doesn't matter what the FDA said.""

I think what Don was saying is that most drugs to hit the market for treating diabetics have been overly glucose-centric. Although these drugs lower glucose, most do not lower the cardiovascular risk (indcidence of MACE), or in many cases actually increase the risk. Don was saying that for these glucose-centric approaches, the FDA still allows a glucose-lowering drug to be registered even if it increases MACE indicence by up to 30%! It's not that the FDA isn't interested in MACE reduction in diabetics....it's just that this has been a challenging group of patients to address. Even with glucose control and LDL-lowering therapy, there is much residual cardiovascular disease risk. Don is emphasizing that the payer groups/health care groups/government bodies/insurance companies would be much more excited and willing to recommend, prioritize and pay for a drug that is shown to reduce MACE, such as RVX-208, in this diabetic population. The recent exception to this trend is Jardiance, which in the EMPA-REG Outcome trial showed glucose lowering AND reduced MACE and the medical field was very excited about this. FDA approval is of course important. Don wasn't saying otherwise. He was simply emphasizing that a drug that is FDA approved but never recommended or prescribed is not going to be successful/profitable.

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