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Message: BETonMACE Enrollment

Koo, I'm not sure if I have understood your question(s) correctly, so please clarify if my answer below misses your point.

Koo wrote "Bear, with that said in your opionion and what is known about  RVX-208, is it able to compare with a statin such as Crestor in plaque regression with not having IVUS measurements?"

Both high-dose Crestor (rosuvastatin, 40 mg daily) and high-dose Lipitor (atorvastatin, 80 mg daily) were shown to reduce plaque volume in the SATURN trial by about 1% percent atheroma volume (PAV) after 2 years. RVX-208 is being administered on top of high-intensity statin therapy (Crestor or Lipitor) in BETonMACE, and RVX-208 was also used on top of statin therapy in ASSURE where they used IVUS. Effects of RVX-208 alone on plaque volume have not been investigated, only in the presence of statin treatment. So in ASSURE (and BETonMACE), the effect of RVX-208 will be on top of whatever plaque volume regression that is already elicited by the statin-therpay received by the placebo group. Post-hoc analysis of ASSURE showed a synergistic effect of RVX-208 with Crestor, moreso than Lipitor, in reducing plaque volume; especially at higher doses of Crestor (20 mg Crestor and 40 mg Lipitor were the highest used in ASSURE). See the 2013 news release for a refresher). Here's the relevant part:

"Those patients taking Rosuvastatin and RVX-208 had a highly statistically significant Percent Atheroma Volume (PAV) plaque regression of -1.43% with probability value of p<0.002. This PAV regression exceeded the trial's pre-specified PAV endpoint (-0.6%) by more than two-fold. But those patients taking Atorvastatin (Lipitor®) together with RVX-208 had a PAV plaque progression of +0.19% with a non-significant probability value. The synergistic effect of the Rosuvastatin and RVX-208 combination is the basis for two recent provisional patent applications by Resverlogix."

Keep in mind that IVUS measures in ASSURE were after 6 months of treatment. BETonMACE will be at least 12 months of treatment, up to 24 months, with an average treatment of 18 months. SATURN was a 2 year trial and achieved only ~1% reduction in PAV after 2 years. So the magnitude of the plaque reduction by RVX-208 will very likely achieve values beyond those stated in the news release for 6 months of treatment. There is also a good amount of information in the figures for the "COMPOSITIONS AND THERAPEUTIC METHODS FOR ACCELERATED PLAQUE REGRESSION" patent. Importantly, when only those patients with below median HDL are analyzed, one can observe that the synergy of Crestor and RVX-208 on PAV is amplified as the dose of Crestor is increased: 1.43%, 1.64% and 2.04% PAV reduction for those treated with RVX-208 and Crestor at 5 mg, 10 mg and 20 mg daily, respectively. I'm not sure what dose(s) of Lipitor and Crestor are being used in BETonMACE but they do state high-intensity statin treatment in the ClinicalTrials.gov description so could be that most patients get the 20 mg Crestor in BETonMACE. Plus, all patients in BETonMACE will be diabetic AND have very-low HDL.

Koo also wrote: "My understanding of what RVX-208 was all about when I first bought shares in it was because of its ability to do a better job in plaque regression. I may have had the wrong impression with the little I knew of RVX at that time." 

Yes, raising apoAI/HDL and eliciting plaque regression was the early model. Toniv has recently re-visited this topic on Stockhouse in a thread entitled MOA apabetalone (rvx-208) to emphasize how much of a better understanding we have now vs. then of the multiple modes of cardioprotective actions of RVX-208.

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