AP30663 achieved proof of mechanism with first-in-class SK channel inhibition compound in atrial fibrillation – primary endpoint met: 99.9% probability of superiority over placebo
AP31969, a novel compound being developed for sinus rhythm maintenance in atrial fibrillation, commences dosing in phase 1
Copenhagen, Denmark, 13 December 2023 – Acesion Pharma (“Acesion” or “the Company”), a biotech company pioneering first-in-class novel therapies for atrial fibrillation (“AF”), the most common cardiac arrhythmia, today announces the publication of data in Nature Medicine with the full results from its Phase 2 proof-of-concept trial of AP30663, a first-in-class SK ion channel inhibitor for conversion of AF to normal sinus rhythm. As previously announced, the trial met its primary endpoint, thereby demonstrating the first ever proof mechanism for SK channel inhibition as a novel treatment for AF.
AP30663 Phase 2 trial results
In the trial, patients with a current episode of AF lasting for seven days or less were randomized to receive an intravenous infusion of 3 or 5 mg/kg of AP30663 or placebo. The primary endpoint of the trial was cardioversion from AF to sinus rhythm within 90 min from the start of the intravenous infusion, analysed using Bayesian statistics.
The primary endpoint occurred in 42% (5 of 12), 55% (12 of 22) and 0% (0 of 25) of patients treated with 3 mg/kg AP30663, 5 mg kg/1 AP30663, or placebo, respectively. Both doses demonstrated more than 99.9% probability of superiority over placebo, surpassing the prespecified 95% threshold. No ventricular arrhythmias were observed, and adverse event rates were comparable between active and placebo group. The results are now published in the high-impact journal Nature Medicine (https://www.nature.com/articles/s41591-023-02679-9).
AP31969 Phase 1 trial initiated
In addition to the publication of the above phase 2 trial results, the company has also successfully dosed the first healthy volunteer subjects in a phase 1, first-human-dose, clinical trial of AP31969, an oral first-in-class SK ion channel inhibitor designed to maintain sinus rhythm in patients suffering from AF.
The phase 1 trial is planned to consist of two parts: single ascending dose and multiple ascending dose. In addition, the effect of food on the absorption of the compound will be investigated. Results from the trial are expected in Q3 2024.
AP31969 is being developed for chronic oral maintenance treatment to prevent AF recurrence (maintain sinus rhythm) and has shown strong pre-clinical efficacy combined with a promising safety profile.
Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer of Acesion, said “We are pleased that Nature Medicine has recognised the importance of our AP30663 results for conversion of AF to sinus rhythm and accepted them for publication in their prestigious journal. Based on this achievement of clinical proof-of-mechanism, and enabled by our recent successful Series B financing, we have now also moved our oral SK inhibitor AP31969 into clinical development. Through this study, we will learn about the safety, as well as the pharmacokinetics of AP31969 and it is an important step towards addressing the large unmet need within atrial fibrillation.”
AF is the most common type of cardiac arrhythmia and is forecast to affect 25 million people in the US and EU by 2030. Existing drug therapies for AF are associated with the risk of 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. With AP31969, Acesion is aiming to develop a safer alternative.
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For additional information please contact:
Anders Gaarsdal Holst, MD, PhD, Chief Executive Officer
Tel: +45 5240 5266
Optimum Strategic Communications
Mary Clark, Nick Bastin, Hana Malik
Nick Bastin – +44 (0) 79 3150 0066
Hana Malik – +44 (0) 78 5228 8062
About Acesion Pharma
Acesion builds on 20 years of know-how with development of small-molecule SK inhibitors and is the world leader in the field of SK channel inhibition, being the only company able to identify and progress SK channel inhibitors into clinical trials. 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 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’s AP30663 IV is a short acting conversion therapy that has completed a phase 2 trial proving the value of this first-in-class mechanism in AF and thereby de-risking Acesion’s broader SK inhibitor pipeline. Acesion’s oral program with lead candidate AP31969 is designed and engineered using in house knowhow to optimise for, and meet, very high hurdles in both efficacy and particularly safety where existing treatments fall short of patient needs. Acesion Pharma is backed by Novo Holdings, Canaan, Alpha Wave Ventures, Global BioAccess Fund, Wellcome Trust, Broadview Ventures and FC Capital.
About atrial fibrillation (AF)
AF is the most common type of cardiac arrhythmia mainly affecting the elderly population. Lifetime risk for development of AF is estimated at more than one in three. It is forecast to affect 25 million people in the US and EU by 2030. 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.