Acesion Pharma has early clinical evidence that its new approach to treating atrial fibrillation works. In a phase 2 clinical trial, recipients of the biotech’s first-in-class ion channel inhibitor experienced a return to normal heart rhythm, boosting the prospects of a mechanism that could be the first new approach to afib in 20 years.
Copenhagen-based Acesion is trying to treat afib by inhibiting SK ion channels that are involved in the regulation of heart rhythm. Genomewide association studies have found links between genes encoding subtypes of the channel and afib, and animal models have shown that inhibiting SK can convert abnormal heart rhythms and stop them from happening in the first place.
To test whether the approach works in humans, Acesion, which lists Novo Holdings among its investors, ran a phase 2 clinical trial of the SK ion channel inhibitor AP30663 in 63 people with a current episode of afib. Participants received one of two intravenous doses of the drug candidate or placebo.
In the 90 minutes after infusion, more than half of recipients of the highest, 5-mg/kg dose converted to sinus rhythm—the characteristic rhythm of a healthy heart—compared to none of their counterparts in the placebo group, causing the study to hit its primary endpoint. The conversion rate in the low-dose cohort, which received 3 mg/kg, was lower than in the high-dose arm but still significantly higher than in the placebo group.
Today, physicians restore normal heart rhythm through electrical or chemical cardioversion. When giving an energy shock to restore sinus rhythm, physicians give an anesthetic or sedative. To avoid that, some physicians may try the less traumatic chemical conversion first, but it can fail and cause more dangerous abnormal heart rhythms.
In the phase 2 clinical trial, no patients suffered serious adverse events or ventricular arrhythmias, a key safety concern with existing afib treatments. Acesion saw a transient increase in the ECG QTc interval compared to placebo at both doses. The increase was, at worst, comparable to the effects of currently available drugs, according to the biotech.
Acesion attributed the QT effect to off-target inhibition of the hERG ion channel. The biotech has tried to eliminate the effect with its second-generation molecule, which is designed to have higher specificity and is in development as an oral drug for chronic maintenance treatment to prevent afib recurrence.
The chronic maintenance treatment indication is much larger than the cardioversion population covered by the phase 2 clinical trial. Acesion plans to start a phase 1 clinical trial of its chronic candidate in the second half of the year.