Apabetalone, a First-in-Class Epigenetic Therapeutic Candidate, Met Key Endpoint of Lowering Pulmonary Vascular Resistance (PVR) and Was Well Tolerated
Successful Completion and Promising Results of Investigator-led APPROACH-p Trial Sets the Stage for a Larger Multicenter Trial
CALGARY, Alberta, Sept. 08, 2021 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX), a world leader in epigenetics, or gene regulation, today announces that its investigational epigenetic therapeutic apabetalone met the primary endpoint in an investigator led pulmonary arterial hypertension (PAH) pilot study, successfully completing the APPROACH-p trial (Apabetalone for Pulmonary Arterial Hypertension: A Pilot Clinical Study).
“The study successfully achieved its primary objective of confirming the feasibility of the clinical study design and demonstrated encouraging results of apabetalone treatment in patients with PAH. This strongly sets the ground for the planned larger double-blind study,” said Dr. Steeve Provencher, Director of Pulmonary Research, Institute of Cardiology and Respirology of Quebec, Laval University. Dr. Provencher is the lead investigator and sponsor of the trial.
Study Rationale:
Apabetalone is a first-in-class epigenetic therapeutic candidate BET (BRD4) inhibitor which positively regulates and normalizes genes that cause chronic illness. There is strong evidence that BRD4 plays a key role in the pathological phenotype in PAH accounting for disease progression and that BRD4 inhibition can reverse PAH in several animal models. Intriguingly, coronary artery disease (CAD) and metabolic syndrome are more prevalent in PAH compared with the global population, suggesting a link between these diseases. Interestingly, BRD4 is also a trigger for calcification and remodeling processes and regulates transcription of lipoprotein and inflammatory factors, all of which are important in PAH and CAD.
Key Findings:
- Apabetalone treatment was well tolerated with all patients completing trial
- Apabetalone treatment improved key hemodynamic variables on top of standard of care treatment, including the primary endpoint
Study Design:
- Open-label trial including 7 patients with pulmonary arterial hypertension (PAH)
- All patients received oral apabetalone twice-daily for 16 weeks, alongside existing standard of care treatments
- Primary outcome measure:
- Change in pulmonary vascular resistance (PVR) at 16 weeks
- Key secondary outcome measures:
- Change in other metrics of cardiac function (pulmonary artery pressure, cardiac output, right atrial pressure, and mixed venous oxygen saturation) at 16 weeks
- Change in quality-of-life measures (6-min walk distance, WHO functional class, and Emphasis-10 questionnaire) at various timepoints
- Change in plasma biomarkers (including: N-terminal pro-brain natriuretic peptide, alkaline phosphatase, and inflammatory cytokines) at various timepoints
- Patients were limited to those diagnosed with PAH of idiopathic/hereditary origin or associated with connective tissue disease
- More information on the APPROACH-p trial design can be found HERE
Next Steps:
Full trial results will be presented at an upcoming scientific meeting (to be determined). The encouraging results of this study pave the way for the larger multi-centered APPROACH-2 trial, which is expected to begin enrolling patients later this year. APPROACH-2 is a phase 2, randomized, placebo-controlled study of apabetalone for the treatment of PAH.
About Resverlogix
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 COVID-19, 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.
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 APPROACH-2 trial and the potential role of apabetalone in the treatment of patients with pulmonary arterial hypertension (PAH), 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.
Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX).
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