Atrial Fibrillation on the Rise: Challenges and Opportunities for Safer Treatment Options

Atrial Fibrillation (AF) is the most common type of cardiac arrhythmia, affecting an estimated 4.5 million people in Europe alone.

AF mostly affects the elderly population, impacting an estimated 5–10% of people over the age of 70. An ageing population is a key contributor to the rise in AF prevalence, which, in the EU and US combined is predicted to affect 25 million patients by 2030.

AF is associated with an impaired quality of life, an increased rate of hospitalization, and an increased risk of stroke and death. AF-related strokes are currently estimated to account for up to 20% of all strokes. The expected rise in AF patients will also cause a major increase in the economic burden of AF patients.

AF patients are often treated with antiarrhythmic drugs as well as anticoagulants to prevent stroke, but invasive ablation techniques such as pulmonary vein isolation are also used as a treatment in some patients. Antiarrhythmic pharmacological treatments include:

• “Acute cardioversion” of AF, aimed to bring the heart back to its normal rhythm (sinus rhythm)
• “Maintenance therapy”, a chronic drug therapy aimed at maintaining sinus rhythm and preventing the recurrence of AF.

These existing drug therapies generally have a limited effect and are associated with the risk of serious adverse events, hence, there is a considerable patient need for developing better and safer drugs.

Acesion Pharma’s Breakthrough: SK Channel Inhibition Offers New Hope for Atrial Fibrillation Treatment

A Novo Seeds portfolio company, Acesion Pharma ApS, develops more efficacious and safe drugs for the treatment of AF. Acesion Pharma aims to achieve this through novel drugs that inhibit SK ion channels, which are relevant for regulating heart rhythm.

In March of 2023, Acesion announced positive Phase 2 data where clinical proof of mechanism for SK channel inhibition was achieved — increasing the prospects of a mechanism that could be the first new drug approach to AF in 20 years. Subsequently to these Phase 2 data, the Company published compelling pre-clinical data for its second-generation oral SK channel inhibitor, developed for chronic oral maintenance treatment to prevent AF recurrence, in May of this year.

We spoke to Acesion’s CEO, Anders Gaarsdal Holst, MD, PhD, and Partner, Jørgen Søberg Petersen of Novo Holdings, to find out about the Company, its recent data, and the outlook for the future.

Anders Gaarsdal Holst, Acesion’s CEO

What is Acesion’s vision?

Acesion Pharma will develop more efficacious and safe drugs for the treatment of Atrial Fibrillation (AF), the most common type of cardiac arrhythmia.

What advances does Acesion bring to addressing this unmet medical need?

Existing drug therapies generally have a limited effect and are associated with risk of serious adverse events. However, Acesion’s science is based on the novel concept of treating Atrial Fibrillation (AF) by inhibiting the SK channels. SK channels are ion channels present in the heart where they are relevant for regulating the heart rhythm. Acesion and others have generated data showing that inhibiting these channels results in antiarrhythmic effect while avoiding the safety issues of the existing therapies, namely a risk of causing life-threatening cardiac rhythm disturbances (proarrhythmia). This is the first new pharmacological approach to treating AF in the last 20 years.

How does AP31969 differ from current available treatments on the market?

AP31969 is a molecule that besides being a potent SK inhibitor is also optimised for removing a lot of the barriers that the existing drugs have for their use. We have ensured that it has a low risk of drug-drug interaction as AF patients are often on a lot of other medications. In essence, what we are aiming for with this molecule is to make it safer for patients and easier to prescribe for the physicians and with this, opening up a much more widespread use of drugs to treat AF.

What does the preclinical data mean for Acesion?

The preclinical data generated has shown that AP31969 has a low risk of proarrhythmia with robust differentiation compared to existing drugs. This indicates that AP31969 has an improved cardiac safety profile and provides us with confidence in our plans to progress to a phase 1 trial.

What’s next for Acesion? What are the upcoming milestones we can we expect to see from Acesion in the next 12 months?

Upon the positive preclinical results, Acesion has completed toxicology studies for AP31969 in preparation for the phase 1 trial we anticipate to begin within this year (2023).

What is the potential impact of Acesion’s lead therapeutic in Atrial Fibrillation?

With the numbers suffering from AF 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. Acesion’s 2nd generation molecule shows great potential for this novel class of compounds for the treatment of chronic AF and will hopefully be able to expand the use of pharmacological therapy for AF.

Jørgen Søberg Petersen, MD, PhD, MBA, Partner at Novo Holdings

What excites you about Acesion Pharma?

Acesion is developing a new, novel approach to treating AF, a condition forecast to affect 25 million people in the US and EU in 2030. These impressive, first-in-class, clinical proof-of-concept data for its second-generation asset significantly de-risks the Company’s SK channel inhibitor program — the first new approach to treating AF in 20 years.

What does the future look like for patients with AF?

Currently, drug therapy for AF is cumbersome and associated with the risk of serious side effects. However, if Acesion succeeds with developing AP31969, this will be a gamechanger as it will be easier for physicians to prescribe these drugs to treat their AF patients.

What made Acesion stand out?

Acesion’s technology is based on basic research initiated in 2008 at University of Copenhagen and drug discovery and chemistry insights from the Company NeuroSearch. This provided Acesion with a strong scientific foundation along with a fantastic management team, which we saw great potential in.

What was Novo Holdings’ role in the start of the Company?

Novo Holdings initially invested in Acesion in December 2011 and remains the largest shareholder. In addition to capital, Novo Holdings has consistently provided access to professional guidance and know-how, which has been critical for the successful development and transformation of Acesion from a start-up to a fully integrated biotech company.