Results of Phase 2B trials of GENETIC-AF published in the Journal of the American College of Cardiology: Heart Failure

<p class = "web-atom canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "WESTMINSTER, Colorado, May 01, 2019 (GLOBE NEWSWIRE) – ARCA biopharma, Inc. (ABIO), a biopharmaceutical company applying a precision medicine approach to the development of genetically targeted therapies against cardiovascular disease, announced today the publication of the article "GENETIC-AF: Bucindolol for the maintenance of sinus rhythm in a population of heart failure patients defined by the genotype " published in JACC: heart failure, Journal of the American College of Cardiology.
"data-reactid =" 11 "> WESTMINSTER, Colorado, May 1, 2019 (GLOBE NEWSWIRE) – ARCA Biopharma, Inc. (ABIO), a biopharmaceutical company that applies a precision medicine approach to the development of genetically targeted treatments for cardiovascular disease, announced today that the article "GENETIC-AF: Bucindolol for maintaining sinus rhythm in a population with genotype-defined heart failure" was published in JACC: heart failure, Journal of the American College of Cardiology.

<p class = "canvas-atom canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "The main author of the document is Jonathan P. Piccini, MD, MHS, FACC, Director, Duke Center for Atrial Fibrillation, Duke University Medical Center and Duke Clinical Research Institute and the main author is Stuart J. Connolly, MD, Professor Emeritus, Division of Cardiology at McMaster University Data-reactid = "12"> The lead author of the paper is Jonathan P. Piccini, MD, MHS, FACC, director of the Duke Center for Atrial Fibrillation, Duke University Medical Center and the University of Toronto. Duke Clinical Research Institute, as well as the main author is Stuart J. Connolly, MD, Professor Emeritus, Division of Cardiology at McMaster University in Hamilton, Ontario.

<p class = "canvas-atom-canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "" Atrial fibrillation (AF) is a common problem and serious medical problem associated with significant morbidity and mortality, especially in patients with heart failure ", Dr. Michael R. Bristow, President and CEO of ARCA and co-author of the document. & Nbsp; "The development of AF is associated with an increased risk of adverse cardiovascular consequences, and when AF occurs in patients with HF, these side effects are accentuated. & Nbsp; AF and FH often coexist and have common risk factors, as well as overlapping pathophysiologies. "" Data-reactid = "13"> "Atrial fibrillation (AF) is a common and serious medical problem associated with significant morbidity and mortality, especially in patients with heart failure," he said. Dr. Michael R. Bristow, President and CEO of ARCA and co-author of the document. "The development of AF is associated with an increased risk of adverse cardiovascular consequences, and when AF occurs in patients with FH, these side effects are accentuated. AF and FH often coexist and have common risk factors, as well as overlapping pathophysiologies. "

<p class = "canvas-atom-canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients who have the beta-one adrenergic receptor (ADRB1) Arg389Arg GENETIC-AF compared the effectiveness of bucindolol and metoprolol succinate for the maintenance of sinus rhythm in a genetically-defined HF population with AF. 267 HF patients with left ventricular ejection fraction (LVEF) < 0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype. The primary endpoint of AF/atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period." data-reactid="14">Bucindolol is a beta-blocker whose unique pharmacological properties provide greater benefit in HF patients with Arg389Arg adrenergic beta-one receptor (ADRB1) genotype. GENETIC-AF compared the efficacy of bucindolol succinate and metoprolol for maintaining sinus rhythm in a genetically defined HF population with AF. The study recruited 267 patients with heart failure with a left ventricular ejection fraction (LVEF) <0.50, a symptomatic AF and the ADRB1 Arg389Arg genotype. The primary endpoint of AF assessment / atrial flutter or all-cause mortality was assessed by electrocardiogram (ECG) over a 24-week period.

The risk ratio (HR) for the primary endpoint was neutral (1.01 (95% CI: 0.71, 1.42)), but trends in bucindolol benefit were observed in several subpopulations. Precise therapeutic phenotyping revealed that a differential response to bucindolol was associated with: 1) the time interval between the initial diagnosis of HF and FA and randomization, and: 2) l & lt; Occurrence of AF compared to the initial diagnosis of HF. In a cohort whose first diagnoses of IC and AF were less than 12 years prior to randomization, in which the onset of AF did not precede the IC over 2 years (N = 196), the HR was 0.54 (95% CI: 0.33, 0.87, p = 0.011). In addition, in the group of patients with an average LVEF subpopulation, which included approximately 50% of the randomized patients, the HR was 0.42 (0.21, 0.86); p = 0.017.

<p class = "canvas-atom-canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "As expected based on its unique pharmacology, bucindolol reduced plasma venous norepinephrine levels (by 124 pg / ml at 4 weeks, p <0.001) while metoprolol did not (p =0.30). Plasma NT-proBNP, a biomarker of both AF and HF, was reduced in the bucindolol group at 4 weeks (p= 0.003), 12 weeks (p = 0.002) and 24 weeks (p = 0.005) while in the metoprolol group a reduction was observed only at 24 weeks (p = 0.014)." data-reactid="16">As expected based on its unique pharmacology, bucindolol reduced noradrenaline plasma levels in the veins (124 pg / ml at 4 weeks, p <0.001), whereas metoprolol (p = 0.30) was reduced. Plasma NT-proBNP, a biomarker of both AF and HF, was reduced in the bucindolol group at 4 weeks (p = 0.003), 12 weeks (p = 0.002) and 24 weeks (p = 0.005), while only in the metoprolol group was observed only at 24 weeks (p = 0.014).

"In this exploratory phase 2 trial, bucindolol pharmacogenetically-guided therapy did not reduce the recurrence of AF / AFL / ACM compared with metoprolol in a large population of patients with HF who presented with risk of AF, "concluded Dr. Piccini. patients participating in this trial demonstrated a more favorable response to genetically targeted bucindolol compared to standard beta-blocker therapy. These data are very encouraging and deserve to be studied in future phase 3 trials. "

"The precision therapeutic phenotyping methodology used in these analyzes identified extensive relationships that consistently manifested throughout the dataset," commented Christopher Dufton, PhD, vice president of clinical development at ARCA. and co-author: "We believe that this approach the likelihood of reproducibility of these results in future phase 3 trials."

<p class = "canvas-atom canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "About ARCA biopharma"data-reactid =" 19 ">About ARCA biopharma

<p class = "web-atom canvas-text Mb (1.0em) Mb (0) – sm Mt (0.8em) – sm" type = "text" content = "ARCA biopharma is dedicated to the development of genetically targeted therapies The main ARCA's candidate product, GencaroTM (bucindolol hydrochloride), is a pharmacologically unique beta-blocker and a moderate vasodilator developed for the potential treatment of atrial fibrillation in patients with heart failure ARCA has identified common genetic variations that, in his opinion, can predict the individual response of patients to Gencaro, giving him the potential to become the first genetically targeted AF prevention treatment. & nbsp; The Gencaro development program has has been approved by the FDA as an accelerated procedure ARCA is also developing AB171, a thiol-substituted isosorbide mononitrate, as a genetically targeted treatment for heart failure e and peripheral arterial disease (PAD). information, please visit www.arcabio.com. "data-reactid =" 20 "> ARCA biopharma is dedicated to the development of genetically targeted therapies for cardiovascular diseases through a precision medicine approach to drug development. -blocker and light vasodilator under development for treatment atrial fibrillation potential in heart failure patients with a mean ejection fraction, ARCA has identified common genetic variations that, in his opinion, predict a patient's response to Gencaro, giving him the potential to To be the first The Gencaro development program has been FDA-approved Fast Track and ARCA is also developing thiol-substituted isosorbide mononitrate (AB171), as a genetically targeted treatment for heart failure and heart failure. Peripheral Arterial Disease (PAD) For more information, please visit www.arcabio.com.

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