Resverlogix Corp. has announced findings from the recent analysis of Major Adverse Cardiovascular Events (MACE) data in patients with diabetes mellitus (DM) enrolled in both the ASSURE and SUSTAIN trials.
In ASSURE, MACE was a pre-specified endpoint and it was confirmed to be statistically and significantly reduced in patients with DM treated with RVX-208 vs. placebo.
The latest finding reinforces the potential benefit of RVX-208, a first in class BET-inhibitor, to impact MACE and additional metabolic parameters over a duration of 6 months in high risk vascular patients with DM and low HDL.
ASSURE enrolled a population who had high cardiovascular risk with low HDL-C and amongst these almost 100 patients had DM. Approximately 75% (precise numbers here and below are reserved for future publications and abstracts) of these patients with DM were given RVX-208 while the remainder received placebo.
Unexpectedly, we noted a statistically significant relative risk reduction in MACE of more than 65% in patients with DM treated with RVX-208 vs. placebo. While this marked and significant reduction of MACE in the ASSURE data alone is already very important, it is further supported by the analysis of data from SUSTAIN, a trial with a population almost identical to that in ASSURE.
When data from both ASSURE and SUSTAIN were pooled, patients with a history of DM totaled almost 200. Roughly 2/3 of these patients received RVX-208 while the remainder were given placebo. Analysis of the pooled patient data showed again that RVX-208 treatment led to a statistically significant relative risk reduction in MACE of >65% vs. placebo. In patients with DM, RVX-208's ability to reduce MACE is very important because the majority of the patients die from cardiovascular diseases.
In the ongoing analysis of pooled ASSURE and SUSTAIN data, many biomarkers of cardiovascular risk were examined but the above findings made blood glucose levels of specific interest. Results of analysis showed that patients with DM given RVX-208 tended to have lower blood glucose vs. placebo.
But specifically in patients with DM who had low HDL, the blood glucose was significantly lower following treatment with RVX-208 vs. placebo. Furthermore, the time required for RVX-208 to reduce blood glucose was not observed until at least 12 weeks following initiation of treatment.
While the analyses of ASSURE data was being conducted, a new trial looking at metabolic parameters was in progress conducted at the Baker IDI Heart and Diabetes Institute (Melbourne, Australia). The investigators 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).
Patients (n=23) with pre-diabetes mellitus (also called metabolic syndrome) were enrolled in the study and given 200 mg/day RVX-208 for a short duration of only 4 weeks. The preliminary results were not consistent with their hypothesis. However, this finding was useful in understanding the ASSURE data because for RVX-208 to reduce blood glucose in patients with DM required at least 12 weeks of treatment.
Analysis of data from the new trial beyond preliminary results reported here will include; HDL abundance, lipidomics, platelet aggregation, monocyte activation and neutrophil adhesion. Resverlogix is planning to submit the above important findings and other new data to scientific journals for peer review prior to publication and presentation at leading medical conferences.
"Resverlogix will continue to examine in detail the data from its numerous human clinical trials specifically for important biomarkers that may play a role in high risk vascular diseases such as acute coronary syndrome, type 2 diabetes mellitus and chronic kidney disease" stated Donald McCaffrey, President and Chief Executive Officer of Resverlogix. "These are new and important findings that RVX-208, when added to standard of care medicine, reduces MACE in patients with DM" added McCaffrey.
"The new observations above and continued analysis of our extensive database are very important for establishing the emerging role of BET inhibition in high risk vascular disease and especially in those with DM" stated Dr. Jan Johansson, Senior Vice President of Medical Affairs at Resverlogix. "The new information that we have gained was essential in designing the next RVX-208 clinical trial to facilitate product registration" Dr. Johansson further commented.