Acesion Pharma starts Phase 2 trial of AP31969 in patients with atrial fibrillation

AP31969 is a novel, first-in-class, oral SK ion channel inhibitor intended for rhythm control of atrial fibrillation and has recently completed Phase 1 in healthy volunteers

Phase 2 trial will assess the efficacy of AP31969 on atrial fibrillation burden and its safety profile using continuous cardiac rhythm monitoring

COPENHAGEN, Denmark, Jan. 6, 2026 /PRNewswire/ -- Acesion Pharma ("Acesion" or "the Company"), a biotech company pioneering treatments for atrial fibrillation ("AF"), the most common cardiac arrhythmia, today announces enrolment of the first patients in its randomized, double-blind, placebo-controlled, dose finding  Phase 2 clinical trial (NCT07267949), designed to assess the efficacy and safety of AP31969 in AF patients. The trial will enrol 200 patients across eight European countries, with anticipated completion by Q1 2027.

The primary efficacy endpoint in the trial is AF burden, defined as the percentage of time a participant is in AF. A key safety endpoint is the occurrence of proarrhythmia episodes in the ventricles of the heart. Ventricular proarrhythmia represents the key safety limitation of currently available antiarrhythmic drugs. To enable robust evaluation of these endpoints, participants will receive an implantable loop recorder, allowing for continuous 24/7 cardiac rhythm monitoring.

In 2025, Acesion successfully completed a phase 1 clinical trial of AP31969 in 92 healthy volunteers (NCT06066099). The trial included a single ascending dose (SAD) and a multiple ascending dose (MAD) part and was designed to evaluate safety, pharmacokinetics and effects on the QT interval (QTc). Prolongation of QTc is a well-established ECG marker of proarrhythmia risk. AP31969 demonstrated a favourable safety profile and pharmacokinetics suitable for chronic oral administration. Importantly, the trial demonstrated that clinically relevant effects of AP31969 on QTc could be ruled out, supporting a favourable safety profile of AP31969 with respect to proarrhythmia risk – a major concern with current antiarrhythmic drugs.

Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer of Acesion, said: "Advancing our oral lead compound AP31969 into a Phase 2 clinical trial marks an important milestone for Acesion. With the use of implantable loop recorders in the trial, we can precisely estimate AF burden efficacy, as well as understand the risk of proarrhythmia. Being able to robustly understand both the efficacy and the key safety parameter within a therapy class is unusual in a phase 2 cardiovascular trial and, if successful, will greatly de-risk Phase 3 development and accelerate AP31969's path to becoming the preferred treatment option for the increasing number of patients suffering from AF."

Acesion Pharma is a leading company in the development of novel therapies for AF with a focus on improving the everyday lives of millions of patients worldwide. With increasing disease incidence, the AF patient population in US and EU combined is expected to reach 25 million in 2030. Acesion has pioneered the development of SK ion-channel inhibitors, and AP31969 is positioned to become a future first-line option for AF treatment by addressing the major safety limitation of proarrhythmia associated with existing therapies.  

About Acesion Pharma

Acesion builds on 20 years of know-how within development of small-molecule SK inhibitors and is developing this novel mechanism for rhythm control of atrial fibrillation (AF).

In pre-clinical studies, inhibiting the SK channels has been shown to result in pronounced antiarrhythmic effects in the heart's atria while avoiding detrimental effects in the ventricles, the major chambers of the heart and the source of most safety issues with existing drugs. Furthermore, 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.

Acesion is the only company successfully progressing SK inhibitors into clinical trials and has demonstrated robust efficacy with its first-generation SK channel inhibitor AP30663 in pharmacological AF cardioversion (https://www.nature.com/articles/s41591-023-02679-9). Acesion's oral SK channel inhibitor AP31969, which is now being tested in a phase 2 trial, has been designed in-house to achieve AF efficacy without compromising on safety. AP31969 is as an oral chronic therapy positioned to become a future first-line option for AF treatment by addressing the major safety limitation of proarrhythmia associated with existing therapies. 

Acesion is backed by Novo Holdings, Canaan, Alpha Wave Ventures, Global BioAccess Fund, Wellcome Trust, Broadview Ventures and FC Capital.

https://www.acesionpharma.com/ 

About atrial fibrillation (AF)

AF is the most common type of cardiac arrhythmia. With increasing disease incidence, the patient population in US and EU combined is expected to reach 25 million in 2030. Lifetime risk for development of AF is estimated at more than one in three. AF is characterized by chaotic electrical activity in the upper chambers of the heart, the atria, resulting in an irregular and high heart rate. AF is associated with impaired quality of life, increased rate of hospitalization, and a five-fold increased risk of stroke. Increasing evidence suggests that patients with AF also face a higher risk of cognitive dysfunction and dementia.

Existing drug therapies for rhythm control of AF (antiarrhythmic drugs) are associated with risk of very serious cardiac or other adverse effects, resulting in a great need for safer drugs. Yet, there has been a lack of innovation and development with no new chronic AF drug approved for nearly 20 years.

A landmark New England Journal of Medicine published clinical trial has shown that rhythm control improves survival and long-term outcomes for AF patients, further underlining the need for safer ways to achieve this (https://doi.org/10.1056/NEJMoa2019422).