The primary endpoint has been achieved in a Phase II trial of AP30663, a first-in-class SK ion channel inhibitor for conversion of atrial fibrillation (AF) to normal sinus rhythm.
Acesion Pharma enrolled 63 patients with a current episode of AF in the trial and tested two intravenous doses of AP30663, 3 and 5mg/kg, compared to placebo. The primary endpoint was the proportion of patients with AF conversion to sinus rhythm within 90 minutes of infusion start.
The proportion (conversion rate) for AP30663 5mg/kg exceeded 50% with no conversions observed for placebo and with a numerical dose-response between the 3 and 5mg/kg dose. The trial employed a Bayesian analysis and there was a probability (posterior probability) >99.9% of a true AF conversion rate greater than placebo for each of the two doses.
These results were supported by a traditional analysis of the primary endpoint, demonstrating highly significant P-values for each of the two doses compared to placebo.
The treatment was also well tolerated, with no serious adverse events (AEs) reported in the AP30663 groups.
Great unmet need
John Camm, Acesion SAB member and Emeritus Professor of Clinical Cardiology, St. George’s University of London, said: “With the numbers suffering from atrial fibrillation forecast to grow dramatically in the coming years, and with the many safety issues associated with currently available drugs, there is a great unmet need for safer AF treatments that can decrease the risk for patients, but also remove barriers for physicians wanting to keep their patients in sinus rhythm by treating them with an antiarrhythmic drug. This novel mechanism holds the promise to deliver on these aspects.”
In pre-clinical studies, inhibiting the SK channels has been shown to result in pronounced antiarrhythmic effects in the atria while avoiding effects on the ventricles, the major chambers of the heart.
Anders Gaarsdal Holst, Chief Executive Officer of Acesion, commented: “This clinical trial has proven the general mechanism of action of SK channel inhibition for treatment of atrial fibrillation. It further de-risks our pipeline of small molecule SK inhibitors, including AP31969, our ongoing second generation oral lead programme, which targets the much broader and chronic treatment indication of sinus rhythm maintenance and which is planned to start Phase I in H2 2023.”