MACE in the Chronic Kidney Disease group was reduced by 50%
CALGARY, Alberta, June 09, 2020 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix") (TSX:RVX) is pleased to announce key data from its BETonMACE clinical trial in pre-specified stage 3 chronic kidney disease (CKD) patients. This data was presented in a virtual oral plenary session at the 57th ERA-EDTA Virtual Congress this morning by Dr. Kam Kalantar-Zadeh, MD, MPH, PhD, Professor and Chief, Division of Nephrology, Hypertension, and Kidney Transplantation, University of California Irvine, California, USA. The presentation was titled, “Effects of the bet-inhibitor apabetalone on cardiovascular events in patients with type 2 diabetes mellitus and acute coronary syndrome, according to presence or absence of chronic kidney disease. A BETonMACE trial report.”
In the BETonMACE clinical trial comparing the effects of apabetalone to placebo on major adverse cardiovascular events (MACE) and hospitalization for congestive heart failure (CHF) in patients with type II diabetes and recent Acute Coronary Syndrome (ACS), a total of 288 participants with CKD, defined by a glomerular filtration rate (GFR) below 60 mL/min/1.73 m² at baseline were evaluated in a pre-specified subgroup. In the CKD group, dramatic event reduction was observed for MACE in apabetalone (13/124 [10.5%]) vs. placebo (35/164 [21.3%]) with a hazard reduction of 50% (95% confidence interval [CI]: 4%-74%, p=0.03), and 74% (95%CI: 6%-93%, p=0.03) for CHF hospitalizations. For the composite endpoint of MACE and hospitalization for CHF, the observed hazard reduction for the subgroup was 52% (95%CI: 11%-74%, p=0.02).
“For the first time in patients with a recent Acute Coronary Syndrome with diabetes and stage 3 CKD co-morbidities, we observed a 50% reduction of MACE by a medication, apabetalone treatment. This is important as this patient population is known to have significantly higher CVD risk compared to non-CKD patients and being less or non-responsive to the standard of care or other emerging therapies,” stated Dr. Kam Kalantar-Zadeh. “This was a pre-specified analysis from the Phase 3 BETonMACE trial. Further clinical studies are warranted on the effect of apabetalone in high risk CVD populations such as patients with other stages of CKD where there remains a critical unmet medical need.”
In the fall of 2019, Resverlogix reported results from its Phase 3 trial BETonMACE. BETonMACE was a clinical trial that tested apabetalone treatment to impact primary MACE on 2,425 CVD patients with diabetes and a recent acute coronary syndrome event. The trial in its primary endpoint of primary MACE in the entire population had a hazard reduction of 18% versus placebo. In the pre-specified CKD sub population, apabetalone significantly reduced both primary MACE and hospitalizations due to congestive heart failure in comparison to placebo with top standard of care. Apabetalone’s consistent safety profile was further validated by an analysis of adverse events in BETonMACE, and nine positive reports by the trial’s independent Data and Safety Monitoring Board.
About CKD and MACE Risk
The high proportion of MACE risk in CKD patients has been reported in a large longitudinal follow-up study reported by Keith et al. (Arch Intern Med. 2004) on over 27,000 Managed Care patients with CKD, which focused on understanding the natural history of chronic kidney disease with regards to progression to renal replacement therapy (transplant or dialysis) and death in a representative patient population, recorded the prevalence of the following comorbidities at the index date and end point: hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, hyperlipidemia, and renal anemia. Their data showed that the rate of renal replacement therapy over the 5-year observation period 1.3%, and 19.9%, respectively, for the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) stages 3 and 4, and that the mortality rate was 24.3%, and 45.7%. Thus, death was far more common than dialysis at all stages.
Similar finding to this analysis was reported in the US Renal Data System 2016 analysis where the total number of individuals with CKD Stage 3 in their system was 1,903,500, and far fewer individuals had CKD Stage 4-5; 330,140. One interpretation for the massive difference in CKD3 to CKD4-5 is premature mortality.
Resverlogix is developing apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain and extra-terminal) inhibitor. Apabetalone is the first therapy of its kind to have been granted US FDA Breakthrough Therapy Designation – for a major cardiovascular indication – to help facilitate a time-efficient drug development program including planned clinical trials and plans for expediting the manufacturing development strategy.
BET inhibition is an epigenetic mechanism that can regulate disease-causing genes. Apabetalone is a BET inhibitor selective for the second bromodomain (BD2) within the BET proteins. This selective inhibition of apabetalone on BD2 produces a specific set of biological effects with potentially important benefits for patients with high-risk cardiovascular disease, diabetes mellitus, chronic kidney disease, end-stage renal disease treated with hemodialysis, neurodegenerative disease, Fabry disease, peripheral artery disease and other orphan diseases, while maintaining a well described safety profile.
Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX).
Follow us on:
- Twitter: @Resverlogix_RVX
- LinkedIn: https://www.linkedin.com/company/resverlogix-corp-/
For further information please contact:
This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information related to the potential role of apabetalone in the treatment of patients with high-risk cardiovascular disease, diabetes mellitus, chronic kidney disease, end-stage renal disease treated with hemodialysis, cognitive disorders, Fabry disease, peripheral artery disease and other orphan diseases. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.