Acesion Pharma announced positive pre-clinical data for AP31969 today (May 15) and said its second-generation oral SK channel inhibitor was developed for chronic oral maintenance treatment to prevent AF recurrence.
The company said it aims to develop a novel drug for AF that solves the major concern with existing drugs; a high-risk of life-threatening cardiac arrhythmia, also known as proarrhythmia.
It said that to refine drug proarrhythmia risk prediction; regulators, academics, and industry have collaborated on developing pre-clinical models with this specific purpose.
AF is the most common type of treated heart arrhythmia - when the heart beats too slowly, too fast, or in an irregular way.
When a person has AF, the normal beating in the upper chambers of the heart - the two atria is irregular, and blood doesn’t flow as well as it should from the atria to the lower chambers of the heart - the two ventricles. AFib may happen in brief episodes, or it may be a permanent condition.
It was reported that in two such models, AP31969 has demonstrated a low risk of proarrhythmia with robust differentiation to existing drugs, which have a high risk of proarrhythmia, tested in the same models.
Further results from pre-clinical studies, Acesion said, showed that AP31969, tested at expected supratherapeutic doses across two in-vivo large animal models, has no prolongations of the corrected QT interval, a well-established marker of proarrhythmia risk.
The researchers said that in addition to its promising cardiac safety profile, AP31969 has demonstrated good oral pharmacokinetic properties across different animal species and a low-risk of causing drug-drug interactions, another significant issue with existing drugs.
AP30663, Acesion’s first-in-class SK ion channel inhibitor for conversion of AF to normal sinus rhythm, recently demonstrated robust efficacy in patients with AF. AP31969 has shown strong and similar efficacy to AP30663 in two animal models, supporting that efficacy can be expected to be shared across the two compounds.
Finally, AP31969 has recently completed the toxicology studies required by regulatory authorities, ahead of the phase 1 trial which Acesion plans to start in H2 2023.
Anders Gaarsdal Holst, chief executive officer of Acesion, said: “With a growing number of patients suffering from atrial fibrillation, there is a significant need for treatment. Unfortunately, all existing drugs have major safety issues that endanger patients.
“Acesion’s positive pre-clinical results support that AP31969 has the potential to solve these issues and greatly broaden the use of pharmacological treatment within atrial fibrillation. We are excited to continue the development of AP31969 with a phase 1 clinical trial and look forward to the continued progress we will make in the coming year.”
The company said that pre-clinical studies have shown pronounced antiarrhythmic effects in the atria while avoiding effects on the ventricles, the major chambers of the heart and the source of most safety issues with existing drugs, when inhibiting the SK channels.
Further, it said, the SK channel has strong genetic validation with genes encoding the SK channels having one of the strongest associations to AF in human genome-wide association studies.
