Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX), a world leader in epigenetics, or gene regulation, announces today new data that demonstrates their first-in-class oral small molecule BET inhibitor candidate Apabetalone significantly improves cognition and reduces cognitive decline among high-risk patients with cardiovascular disease (CVD) and diabetes mellitus.
The study findings were published in the peer-reviewed Journal of Alzheimer's Disease, titled: “Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified MoCA Analysis Nested in the BETonMACE Randomized Controlled Trial.”
These findings suggest that the BET inhibitor Apabetalone holds promise as a safe and effective therapeutic avenue for vascular cognitive impairment. Apabetalone, an epigenetic therapeutic, is the first-in-class oral investigational BET inhibitor which positively regulates and normalizes genes that cause chronic illness.
These findings are a sub-study of the previously published BETonMACE cardiovascular disease (CVD) outcome study. Previously reported BETonMACE study details can be found using the following LINK.
“The exploratory pre-specified cognition analysis of BETonMACE suggests that Apabetalone represents a promising new therapeutic approach for patients with vascular cognitive impairment,” said Dr. Jeffrey L. Cummings, Vice Chair of Research, University of Nevada, Las Vegas, Department of Brain Health, and the lead author of the new peer-reviewed study. “A large unmet need remains in this population and finding safe and effective ways to prevent, or reverse cognitive decline is a global research priority,” further stated Dr. Cummings.
“Our interpretation is that favorable vascular effects in the brain tissue treated with apabetalone translates to improved cognition, which we had anticipated,” stated Donald McCaffrey, President and Chief Executive Officer. “We were extremely pleased to see that the effect was found in the group that needed it the most – those with cognitive impairment at the start of the study, thus adding a distinct treatment bonus effect to the CVD patients with diabetes,” Mr. McCaffrey continued.
Study Highlights and Conclusion:
- In patients with baseline MoCA score ≤ 21, indicating cognitive impairment, Apabetalone treatment resulted in a significant 2.1 unit increase in MoCA score (p=0.02) – a clinically meaningful improvement when compared with the placebo group.
- Alkaline phosphatase (ALP), a biomarker whose abundance is associated with cognitive decline, was reduced in the Apabetalone-treated group, relative to placebo (p=0.03).
- This analysis highlights the continuing unmet need for treatment options for vascular cognitive impairment in high-risk cardiovascular patients with diabetes. The Apabetalone associated improvement in MoCA scores suggests that BET inhibition holds promise as a safe and effective therapeutic avenue for vascular cognitive impairment.
- Risk of vascular cognitive impairment increases with age, cardiovascular disease (CVD), diabetes, and chronic kidney disease.
- The effect of apabetalone treatment on cognition in a high-risk diabetic and CVD population was investigated in a prespecified analysis of the placebo-controlled BETonMACE trial.
- Patients 70 years and older (464 patients) were administered the Montreal Cognitive Assessment (MoCA) at baseline and yearly to monitor changes in cognition.
Apabetalone (RVX-208), is a first-in-class, oral small molecule epigenetic, or gene regulating, therapeutic candidate. It is a selective BET (bromodomain and extra-terminal) inhibitor, which works by turning genes on and off. The prevalence of BET proteins in the human body allows apabetalone, through its unique mechanism of action, to simultaneously target multiple disease-causing biological processes while maintaining a well described safety profile – leading to a new way to treat chronic disease.
In February 2020, apabetalone is the first therapy of its kind to receive Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) – for a major cardiovascular indication – following the groundbreaking findings from the BETonMACE Phase Three study showing apabetalone can prevent major adverse cardiac events among high-risk cardiovascular disease patients who also have type 2 diabetes mellitus.
On March 23, 2020 officially launched its COVID-19 program, enlisting world renowned global collaborators. Studies demonstrate that apabetalone acts against COVID-19 with a unique dual-mechanism: the first pillar of apabetalone’s dual-mechanism is preventing viruses from entering the cells and replicating; the second pillar is averting runaway inflammatory reactions that can cause severe and lasting organ damage. A phase 2 clinical trial is evaluating apabetalone in combination with standard of care for patients hospitalized with COVID-19. Apabetalone treatment could help reduce the severity and duration of COVID-19. Apabetalone’s unique dual-mechanism also means that it is likely to show efficacy against all COVID-19 variants and may even help fight other related viruses.
Apabelalone is the only drug of its class with a well-established safety record in human clinical trials, with well over 4200 patient-years on drug across 10 clinical trials - more long-term safety data than all COVID vaccines combined.
Founded in 2001, Resverlogix is a Calgary based late-stage biotechnology company and the world leader in epigenetics, or gene regulation, with the goal of developing epigenetic therapies for the benefit of patients with chronic disease. Resverlogix is commercializing a new class of therapies, called selective protein inhibitors, designed to regulate gene expression. Through this gene regulation, or epigenetics, of disease-related genes, Resverlogix aims to improve patients’ lives by restoring biological functions – altered by serious illnesses such as cardiovascular disease – back to a healthy state, leading to a new way to treat chronic disease. The Company’s clinical program is focused on evaluating the lead selective protein inhibitor candidate apabetalone for the treatment of cardiovascular disease and associated comorbidities, and COVID-19.