Dr. Norman CW Wong, CSO of Resverlogix presented data on RVX-208 at the European Atherosclerosis Society (EAS) annual meeting in an oral abstract entitled: “RVX-208 a selective bromodomain extra-terminal protein inhibitor reduces MACE in patients with high residual risks of cardiovascular disease, a post-hoc analysis”.
Resverlogix’s Phase 2b clinical trials SUSTAIN and ASSURE revealed that treatment with RVX-208 lead to a marked reduction in major adverse cardiac events (MACE). The addition of RVX-208 (200 mg/day) on top of standard of care therapy including optimal doses of statins in SUSTAIN and ASSURE raised levels of ApoA-I/HDL-c in treated patients.
These changes alone are unlikely to explain the observed MACE reduction. In the search for potential explanations, levels of more than 60 plasma biomarkers were measured in clinical samples collected in the two trials. One of the significant findings was that RVX-208 lowered glucose in patients with diabetes mellitus (DM) who also had low levels of HDL. This finding is intriguing because there are many patients with DM who have low HDL and high CVD risk thus they would benefit from the actions of RVX-208. Furthermore, this glucose lowering action of RVX-208 goes hand in hand with the preliminary observations from our recent trial of subjects with pre-diabetes mellitus completed in Australia.
The presentation also included state-of-the-art microarray data. This technology is a powerful approach to look at how RVX-208 may be beneficial for CVD beyond that provided by biomarker measurements. The technology allows us to analyze and survey thousands of genes for effects of RVX-208. The data collected from primary human hepatocytes showed that RVX-208 attenuated activity of genes in cellular pathways or networks for inflammation, coagulation, complement, cholesterol synthesis and glucose metabolism.
This data reflects our leadership role in understanding selective BET inhibition by RVX-208 in both humans and at the cellular level. The marked reductions of MACE in SUSTAIN and ASSURE provides the foundation for the Company’s planned Phase 3 clinical trial called BETonMACE. The microarray data is most exciting because it provides, at a cellular level, novel insights that detail the multiple activities of RVX-208 beyond its ApoA-I effects in lowering MACE.
