Several Key Proteins That Drive Kidney (Renal) Disease and Dialysis Risk are Downregulated After a Single Dose of Apabetalone

CALGARY, Jan. 23, 2017 /CNW/ - Resverlogix Corp. ("Resverlogix" or the "Company") (TSX: RVX) today announced preliminary results from the New Zealand based Phase 1 trial with severe kidney (renal) impaired patients. The data showed remarkable results in reducing inflamed protein biomarkers in patients with severe kidney impairment versus healthy control patients. It is believed that this is the first time in medical history that a direct connection of this type can be made between epigenetic regulation and its potential for positive disease impact. Both the healthy group and the severely impaired kidney group received equal amounts of apabetalone.

"It was shocking and highly encouraging to see the direct comparison of the protein data ranked by magnitude of effect in the two groups. For the first time, epigenetic and BET inhibition clinical data has been shown to differentially affect genes and proteins between advanced chronic kidney disease (CKD) patients and normal subjects," stated Donald McCaffrey, President and CEO.

Dr. Kamyar Kalantar-Zadeh, Chairman of the Renal Clinical Advisory Board and member of the BETonMACE Clinical Steering Committee stated, "These early results help provide a first understanding of the potential rapid effects of BET inhibition and apabetalone on key proteins that drive risk and death in Stage 4 CKD and potentially dialysis patients. Late Stage 4-5 CKD and dialysis patients represent very important groups whom currently have limited therapeutic strategies that can improve their outcomes and quality of life," Dr. Kalantar-Zadeh added.

Ongoing expanded analysis of this exploratory data is also planned which will look at Ingenuity Pathway Analysis (IPA). The quick onset of action and improvement of reported CKD risk factors are encouraging for the Company in their planned expansion beyond its current cardiovascular and diabetes program. Detailed data will be submitted for peer reviewed publications. 

Clinical Trial Highlights

The study explored acute changes in biomarkers relevant to subjects with Stage 4 CKD. Plasma components were analyzed using the SOMAscan® assay, a sensitive, quantitative and reproducible proteomic tool for measuring 1,310 proteins in the human proteome. Eight patients with previously diagnosed Stage 4 CKD not on dialysis (estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2) were compared to eight matched healthy individuals with normal renal function (eGFR range > 90 mL/min/1.73m2).

Protein data was collected following a single oral administration of 100mg of apabetalone before and after multiple time points in both cohorts. Protein levels of 289 proteins were significantly different at baseline between the two groups (p<0.05). Initial findings from this study revealed a highly differential protein signature at baseline between CKD patients and controls. Following a single dose administration of apabetalone in the Stage 4 CKD patients, the levels of multiple plasma proteins were changed within 12 hours after dosing, demonstrating a fast onset of drug action. Analysis of the changes in protein levels at the 12-hour time point revealed that, in the Stage 4 CKD patients, 33 percent of proteins had statistically significant changes (p<0.05) compared to only 10 percent in the controls. Of these significant proteins, several established renal biomarkers such as interleukin 6 (IL6) and osteopontin, were regulated positively with respect to disease severity and progression.

About Advanced CKD & Dialysis

Advanced CKD encompasses Stages 4 & 5, and it can be alternatively defined as an estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73m2. As reported in the 2016 United States Renal Data System (USRDS) Annual Report, approximately 1.4 million patients in the US have advanced CKD, 474,000 of which are on dialysis treatment. According to the USRDS, advanced CKD cost the US healthcare system approximately US$17 billion in 2014, with an average annual cost exceeding US$28,000 per patient. Additionally, dialysis treatment costs the US Medicare system approximately US$28 billion with an average annual cost exceeding US$80,000 per year. Currently there are no known agents that improve Major Adverse Cardiac Events (MACE) in CKD or dialysis patients.