Resverlogix Corp., a leading epigenetics company, recently presented new clinical results of the mechanism of action of apabetalone (RVX-208) in patients with chronic kidney disease (CKD) and cardiovascular disease (CVD). The studies were presented during the recent American Society of Nephrology (ASN) Kidney Week meeting, held in San Diego, California.
The two posters presented data on apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain and extra-terminal) inhibitor and, according to the company, the only selective BET bromodomain inhibitor in clinical trials. Apabetalone is the first and only BET inhibitor selective for BRD4-BD2, producing a nexus of biological effects while maintaining a well-described safety profile. As such, it has potentially important benefits for patients not only with CKD and CVD, but also with diabetes mellitus, peripheral artery disease, Orphan diseases (PNH), and Alzheimer’s disease.
The first poster, titled “Apabetalone, a First-in-Class Epigenetic BET-Inhibitor, has Effects on Alkaline Phosphatase (ALP) and Estimated Glomerular Filtration Rate (eGFR) in Subjects with CVD and CKD; a Post-hoc Analysis of the ASSERT, SUSTAIN and ASSURE Clinical Trials,” revealed that RVX-208 given to patients who had a baseline eGFR<60 mL/min/1.73 m2 for a period of 12 to 26 weeks resulted in an improved eGFR as well as in a substantial reduction in ALP (alkaline phosphatase level test) test, which measures the amount of alkaline phosphatase enzyme in the bloodstream.
The second presentation, titled “Alkaline Phosphatase Lowering by Selective BET inhibition, a Novel Mechanism for Major Adverse Cardiac Events (MACE) Reduction in High Risk CVD, Diabetes and CKD Patients, a Post-hoc Analysis of Phase 2b Studies with Apabetalone,” drew on data collected in two clinical trials, SUSTAIN and ASSURE, reporting baseline levels of ALP significantly higher in all study patients with major adverse cardiac events (MACE) compared to those without MACE. In an important finding, of 331 patients treated with apabetalone, those patients who suffered from MACE had an increase of ALP by 3 IU/L versus baseline, while in cardiac event-free patients, the levels of ALP decreased by 8 IU/L, showing a significant absolute difference of 11 IU/L between the two study groups.
In addition to the posters, Dr. Kam Kalantar-Zadeh, Professor and Chief, Division of Nephrology and Hypertension at University of California, Irvine, highlighted some of these results during a presentation titled, “Clinical Practice Session: Hot Topics in CKD–MBD: Where Do We Stand in 2015 in Management of Bones and Minerals,” which focused on the relevance of ALP as a prognostic biomarker in patients with chronic kidney and cardiovascular disease. Resverlogix is reviewing these and other results for future publications in a peer-reviewed journal.