neladenoson (BAY 1067197) / Bayer - LARVOL DELTA

Pharmacological Insights Into Safety and Efficacy Determinants for the Development of Adenosine Receptor Biased Agonists in the Treatment of Heart Failure. (PubMed, Front Pharmacol) - "We compare this agent with the well-characterized, pan-adenosine receptor (AR) agonist NECA, capadenoson, and the AR biased agonist VCP746, previously shown to be safe and cardioprotective in pre-clinical models of heart failure. The failure of neladenoson to reach primary endpoints in clinical trials suggests that AR-mediated cAMP inhibition may be a poor indicator of effectiveness in chronic heart failure. This study provides additional information that can aid future screening and/or design of improved AR agonists that are safe and efficacious in treating heart failure in patients."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double-blind, placebo-controlled trial. (PubMed, Eur J Heart Fail) - P2 | "In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function."

Clinical • Journal • P2b data • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

More Purinergic Receptors Deserve Attention as Therapeutic Targets for the Treatment of Cardiovascular Disease. (PubMed, Am J Physiol Heart Circ Physiol) - "The P2YR antagonists such as clopidogrel, ticagrelor and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome...The partial A1R agonist neladenoson and the AR agonist regadenoson have been applied in cardiovascular medicine...The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Heart Failure • Hypertension • Metabolic Disorders

Study to Assess the Safety of BAY1067197 in Stable Heart Failure Patients on Standard Therapy Including ß-blocker (clinicaltrials.gov) - P1/2; N=10; Active, not recruiting; Sponsor: Bayer; Recruiting -> Active, not recruiting

Enrollment closed • Acute Coronary Syndrome • Biosimilar • Heart Failure

Study on the Safety of Neladenoson Bialanate, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug Given as a Single Oral Dose of 10 mg Immediate Release Tablet in Participants With Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight (clinicaltrials.gov) - P1; N=18; Terminated; Sponsor: Bayer

Clinical • New P1 trial

Study on the Safety of Neladenoson Bialanate, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug Given as a Single Oral Dose in Participants With Liver Impairment and Healthy Participants Matched for Age-, Gender-, and Weight (clinicaltrials.gov) - P1; N=22; Terminated; Sponsor: Bayer

New P1 trial

Effect of Neladenoson Bialanate on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. (PubMed, JAMA) - P2; "In light of these findings, novel approaches will be needed if further development of neladenoson for the treatment of patients with HFpEF is pursued. ClinicalTrials.gov Identifier: NCT03098979."

Biomarker • Clinical • Journal

"Neladenoson not beneficial in #HFpEF #CardioTwitter @HFpEF https://t.co/RmgKC5FriI" (@GoHealio)

Neladenoson not beneficial in HFpEF (Healio) - "Sanjiv J. Shah, MD, and colleagues sought to determine whether neladenoson improved exercise capacity, physical activity, cardiac biomarkers and quality of life in patients with HFpEF, and to find an optimal neladenoson dosage leading to significant improvement....'HFpEF is common, is increasing in prevalence, is associated with high morbidity and mortality and lacks effective therapies,' Shah..."

Media quote

"PANACHE: Neladenoson unsuccessful in improving walking distance in HFpEF - #CardioTwitter #ACC19, @HFpEF, @ACCinTouch, @JJheart_doc, @HannaGaggin, @MassGeneral, @HarvardMed https://t.co/0q4eeNijsf" (@CardiologyToday)

Video: PANACHE | ACC.19 (American College of Cardiology) - "Dr. Peter Block interviews presenter Dr. Sanjiv Jayendra Shah regarding PANACHE: Neladenoson Bialanate in HFpEF."

Interview • Video

PANACHE: Neladenoson unsuccessful in improving walking distance in HFpEF (Healio) - "'This is the first randomized controlled trial of a partial adenosine A1 receptor agonist in HF with preserved ejection fraction,' Sanjiv J. Shah, MD...'While there was a good safety profile at 20 weeks, there were slight decreases in renal function and heart rate,' Shah said during the presentation....The take-home message from this is that this study, like many of the other studies in HFpEF necessarily indicates that we may need to take a step back and ask just who we are treating when we say that they have 'HFpEF.' It is increasingly clear...what drug is going to be the relevant challenge."

Media quote

Safety and Efficacy of Neladenoson Bialanate, a Partial Adenosine A1 Receptor Agonist, in Patients with Heart Failure and Preserved Ejection Fraction: Results from the PANACHE Randomized Controlled Trial (ACC 2019) - "Abstract embargoed at this time."

Clinical • Late-breaking abstract