COVID-19 Preclinical Work Continues
CALGARY, Alberta, Aug. 04, 2020 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX) is pleased to announce today the recent publication of an article titled: “Epigenetic modulation by apabetalone counters cytokine driven acute phase response in vitro, in mice and in patients with cardiovascular disease”, in the peer-reviewed Cardiovascular Therapeutics.
The publication can be viewed using the following LINK.
“This publication highlights the cutting-edge research our R&D team continues to pursue to further understand the role BET proteins play in driving cardiovascular disease, and the opportunities for BET inhibitors, like apabetalone, to improve patient outcomes,” said Dr. Ewelina Kulikowski, Senior Vice President, Research & Development at Resverlogix, and the corresponding author of the study. “In moderating the activity of the acute phase response pathway, apabetalone contributes to countering cardiovascular disease processes, and normalizing patient gene expression.
“Although not a topic of the recent publication, the observed effect of apabetalone on cytokine-mediated inflammation in disease processes such as CVD may also impact cytokine overproduction that occurs in other diseases or states, such as during viral infection,” added Dr. Kulikowski. “As a result, we are continuing our preclinical work investigating the effect of apabetalone on COVID-19 infection – first announced on June 1 – as well as other disease states where inflammation may drive disease pathology.”
Publication Highlights include:
- Apabetalone treatment reduces the expression of acute phase response (APR) genes in cultured human liver cells and in mouse models of inflammation
- In patients with stable coronary artery disease (CAD), plasma concentrations of APR proteins, including C-reactive Protein (CRP) are lowered in those who received apabetalone in comparison to those who received placebo with top standard of care
- The select bromodomain and extraterminal (BET) protein inhibition by apabetalone reduces the occupancy of the BET protein BRD4 at the CRP promoter, thereby downregulating its transcription
Publication Background and Conclusions:
APR protein abundance correlates with chronic systemic inflammation, a major contributor to cardiovascular disease progression. The authors conclude that CRP and components of the APR pathway are regulated by BET proteins, and that apabetalone is able to reduce their expression. The findings contribute to a growing understanding of apabetalone’s benefit to CVD patients. Through its epigenetic mechanism, apabetalone has been shown in a number of applications to target markers and pathways associated with cardiovascular disease progression. In the recently completed Phase 3 trial, BETonMACE, apabetalone reduced the hazard of major adverse cardiac events (MACE) by 18% in high-risk cardiovascular disease patients, when compared to placebo with top standard of care.
About BETonMACE and BETonMACE2
In the fall of 2019, Resverlogix reported results from its Phase 3 trial BETonMACE, which tested the beneficial impact of apabetalone treatment on MACE, in a population of 2,425 CVD patients with diabetes and a recent acute coronary syndrome event. The trial found a hazard reduction (HR) of 18% in its primary endpoint – a composite of first MI, stroke and CV death – with apabetalone treatment, when compared to placebo with top standard of care which just missed statistical significance (p=0.11). The HR was improved to 22% when the composite endpoint was broadened post-hoc to include first hospitalization due to congestive heart failure (MACE+CHF) which was significant. In the pre-specified chronic kidney disease sub population, the observed apabetalone benefits were even more dramatic, with statistically significant reductions in both MACE (HR=50%) and MACE+CHF (HR=52%). 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.
As announced on June 22, 2020, the U.S. Food & Drug Administration (FDA) has accepted the Company’s BETonMACE2 clinical plan as a potential registration enabling study with positive implications for Resverlogix and its ongoing partnership discussions. The BETonMACE2 clinical plan was discussed during the Comprehensive Multidisciplinary Initial Breakthrough Therapy Designation (BTD) meeting held between the FDA and Resverlogix on June 2, 2020 following receipt of the company’s Breakthrough Therapy Designation announced on February 3, 2020.
The FDA recommended that all or most BETonMACE2 participants be on a background of top standard of care, including SGLT2i, as clinically indicated. BETonMACE revealed significant, potential synergy with apabetalone and new diabetes drugs including SGLT2i. Among those receiving SGLT2i, a hazard reduction of 60% in the primary endpoint was seen in patients receiving apabetalone and top standard of care, compared to placebo and top standard of care alone.
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).
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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 positive implications to Resverlogix – including its ongoing partnership discussions – based on the acceptance by the FDA of the company’s BETonMACE2 clinical plan as a potential registration enabling study, the observed effect of apabetalone on cytokine-mediated inflammation in disease processes such as CVD, which may also impact cytokine overproduction that occurs in other diseases or states, such as during viral infection, and 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, neurodegenerative disease, 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.