AP30663 / Acesion - LARVOL DELTA

From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics. (PubMed, Eur Cardiol) - "Here, the molecular composition of smallconductance calcium-activated potassium channels and their complex regulation in AF as the basis for understanding the distinct mechanism of action of pore-blockers (apamin, UCL1684, ICAGEN) and modulators of calcium-dependent activation (NS8593, AP14145, AP30663) are summarised. Furthermore, the preclinical and early clinical evidence for the role of small-conductance calcium-activated potassium channel inhibitors in the treatment of AF are reviewed."

Journal • Review • Atrial Fibrillation • Cardiovascular

Inhibition of the K2 potassium channel in atrial fibrillation: a randomized phase 2 trial. (PubMed, Nat Med) - P2 | "AP30663, an inhibitor of the K2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown...K2 channel inhibition may be an attractive mechanism for rhythm control of AF that should be studied further in randomized trials. ClinicalTrials.gov registration: NCT04571385 ."

Journal • P2 data • Atrial Fibrillation • Cardiovascular • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A phase 1 trial of AP30663, a K 2 channel inhibitor in development for conversion of atrial fibrillation. (PubMed, Br J Clin Pharmacol) - "AP30663 in doses up to 8 mg/kg was associated with mild and transient infusion site reactions and an increase of the QTcF interval. Supplementary studies support that the QTc effect may be explained by an off-target inhibition of the I channel."

Journal • P1 data • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2 | N=66 | Completed | Sponsor: Acesion Pharma | Recruiting ➔ Completed | N=108 ➔ 66

Enrollment change • Trial completion • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Acesion Pharma | Trial completion date: Jul 2022 ➔ Apr 2023 | Trial primary completion date: Jun 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Acesion Pharma | Trial completion date: Apr 2022 ➔ Jul 2022 | Trial primary completion date: Mar 2022 ➔ Jun 2022

Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2; N=108; Recruiting; Sponsor: Acesion Pharma; Trial completion date: Jan 2022 ➔ Apr 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2; N=108; Recruiting; Sponsor: Acesion Pharma; Trial completion date: Aug 2021 ➔ Jan 2022; Trial primary completion date: Jul 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (clinicaltrials.gov) - P2; N=108; Recruiting; Sponsor: Acesion Pharma

Clinical • New P2 trial • Atrial Fibrillation • Cardiovascular

First Clinical Study with AP30663 - a K 2 Channel Inhibitor in Development for Conversion of Atrial Fibrillation. (PubMed, Clin Transl Sci) - "In healthy volunteers, no effect of AP30663 was observed on electrocardiographic parameters, other than a concentration-dependent effect on the corrected QT Fridericia's formula interval (+18.8 ± 4.3 ms for the highest dose level compared with time matched placebo). In conclusion, administration of AP30663, a novel K 2 channel inhibitor, was safe and well-tolerated systemically in humans, supporting further development in patients with AF undergoing cardioversion."

Clinical • Journal • Atrial Fibrillation • Cardiovascular

Inhibition of K2 Channels Decreased the Risk of Ventricular Arrhythmia in the Guinea Pig Heart During Induced Hypokalemia. (PubMed, Front Pharmacol) - "In comparison, the structurally and functionally different K2 channel inhibitors, ICA, AP14145, and AP30663 protected the heart from hypokalemia induced VF. These results support that K2 inhibition may be associated with a better safety and tolerability profile than dofetilide."

Journal • Atrial Fibrillation • Cardiovascular

Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man. (PubMed, Front Pharmacol) - "Moreover, AF associated SNPs in KCNN3 influence KCNN3 mRNA expression in human atrial tissue. These properties support continued development of AP30663 for treatment of AF in man."

Journal • Anesthesia • Atrial Fibrillation • Cardiovascular

Mechanisms Of Action Of The KCa2 Negative Modulator AP30663, A Novel Compound In Development For Treatment Of Atrial Fibrillation In Man (RHYTHM 2020) - "AP30663 is a novel negative allosteric modulator of KCa2-channels that concentration-dependently prolonged rodent AERP with minor effects on QT-interval under the present experimental conditions. Moreover, AF associated SNPs in KCNN3 influence KCNN3 mRNA expression in human atrial tissue. These properties support continued development of AP30663 for treatment of AF in man."

Anesthesia • Atrial Fibrillation • Cardiovascular

Inhibition Of KCa2 Channels Decrease The Risk Of Ventricular Arrhythmia In The Guinea Pig Heart During Hypokalemia (RHYTHM 2020) - "Hypokalemia was associated with an increased risk of VF, an effect that was exaggerated by dofetilide. In comparison, the structurally and functionally different KCa2 channel inhibitors, ICA, AP14145 and AP30663 protected the heart from hypokalemia induced VF. These results support that KCa2 inhibition may be associated with a better safety and tolerability profile than dofetilide."

Atrial Fibrillation • Cardiovascular

The K2 Channel Inhibitor AP30663 Selectively Increases Atrial Refractoriness, Converts Vernakalant-Resistant Atrial Fibrillation and Prevents Its Reinduction in Conscious Pigs. (PubMed, Front Pharmacol) - "Both a >30 ms increase of the AERP and conversion of AF occurred in different pigs at a free plasma concentration level of around 1.0-1.4 µM of AP30663, which was achieved at a dose level of 5 mg/kg. AP30663 has shown properties in animals that would be of clinical interest in man."

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