Finerenone (Kerendia®), a first-in-class, orally administered, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA), is being developed by Bayer HealthCare Pharmaceuticals for the treatment of diabetic kidney disease (DKD) and heart failure (HF), including chronic HF (CHF). Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors. Finerenone has been approved in the USA to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage renal disease (ESRD), cardiovascular death, nonfatal myocardial infarction (MI), and hospitalization for HF in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). Finerenone is undergoing regulatory assessment in the EU and in China. A phase III trial is investigating finerenone in patients who have HF with preserved ejection fraction.

Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of heart failure. Neladenoson bialanate maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist. Of particular importance in this clinical development is the potential influence of concomitant use of β-blockers as they have the potential to increase the risk of AV conduction abnormalities with A1R agonist treatment. Two small phase 2a pilot studies evaluating the short-term safety of neladenoson bialanate in patients with HFrEF pretreated with β-blockers have recently completed, and the results are pending (ClinicalTrials.gov identifiers: NCT02040233 and NCT01945606). In a small phase 1 trial in healthy volunteers pretreated with the β-blocker metoprolol succinate, a single 50 mg oral dose of neladenoson bialanate administered together with metaprolol succinate was found to be well tolerated. Notably, no higher degree AV block, prolongation of the PR interval, or relevant decreases in heart rate or systemic blood pressure were observed.

BAY-86-9596 (D-18F-FMT, or O-18F-fluoromethyl-D-tyrosine) was developed as an agent not only for tumor detection but also for monitoring early-phase response to radiation therapy by positron emission tomography (PET). This drug participated in clinical trials for patients with inflammation and solid tumors, but further information about trials is not available.

Ribuvaptan (BAY 868050) is a vasopressin receptor antagonist that has been developed for treatment of heart failure. No information on current use is available.

FLORILGLUTAMIC ACID F-18 is a radioactive L-glutamate derivative and a tumor-specific positron emission tomography (PET) tracer. Orphan designation (EU/3/16/1632) was granted by the European Commission to Piramal Imaging GmbH, Germany, for FLORILGLUTAMIC ACID F-18 for the diagnosis of hepatocellular carcinoma. Currently, it is in phase II trial as a PET tracer in early lung cancer in patients with lung nodules.

Sematilide (CK-1752) was developed as a novel class III antiarrhythmic agent for the arrhythmia treatment. Sematilide blocks the inward rectifier potassium channel (IK1). The further development of the drug was discontinued.

Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of heart failure. Neladenoson bialanate maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist. Of particular importance in this clinical development is the potential influence of concomitant use of β-blockers as they have the potential to increase the risk of AV conduction abnormalities with A1R agonist treatment. Two small phase 2a pilot studies evaluating the short-term safety of neladenoson bialanate in patients with HFrEF pretreated with β-blockers have recently completed, and the results are pending (ClinicalTrials.gov identifiers: NCT02040233 and NCT01945606). In a small phase 1 trial in healthy volunteers pretreated with the β-blocker metoprolol succinate, a single 50 mg oral dose of neladenoson bialanate administered together with metaprolol succinate was found to be well tolerated. Notably, no higher degree AV block, prolongation of the PR interval, or relevant decreases in heart rate or systemic blood pressure were observed.

Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of heart failure. Neladenoson bialanate maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist. Of particular importance in this clinical development is the potential influence of concomitant use of β-blockers as they have the potential to increase the risk of AV conduction abnormalities with A1R agonist treatment. Two small phase 2a pilot studies evaluating the short-term safety of neladenoson bialanate in patients with HFrEF pretreated with β-blockers have recently completed, and the results are pending (ClinicalTrials.gov identifiers: NCT02040233 and NCT01945606). In a small phase 1 trial in healthy volunteers pretreated with the β-blocker metoprolol succinate, a single 50 mg oral dose of neladenoson bialanate administered together with metaprolol succinate was found to be well tolerated. Notably, no higher degree AV block, prolongation of the PR interval, or relevant decreases in heart rate or systemic blood pressure were observed.

Sematilide (CK-1752) was developed as a novel class III antiarrhythmic agent for the arrhythmia treatment. Sematilide blocks the inward rectifier potassium channel (IK1). The further development of the drug was discontinued.