Bayer begins Phase I study with GIRK4 inhibitor for atrial fibrillation
Berlin: Bayer has announced initiation of a Phase I clinical trial with BAY 3670549, an investigational highly selective G-protein-coupled inwardly rectifying potassium channel 4 (GIRK4) inhibitor, which has the potential to help control the electrical activity of heart cells in patients with atrial fibrillation (AFib).
"This investigative approach for rapid cardioversion to normal sinus rhythm is aiming to enable immediate treatment without the need for anesthesia/sedation and electrical shock and to significantly reduce the patients’ time spent in hospital," the company stated in a release.
The first-in-human dose escalation study in a randomized, double-blind, placebo-controlled, group-comparison design will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of BAY 3670549 in healthy participants. AFib is the most common type of cardiac arrhythmia (irregular heart rhythm), affecting more than 60 million people worldwide, and a significant risk factor for stroke and heart failure.
“Initiating clinical development of our investigational GIRK4 inhibitor marks an important milestone of our ambition transforming atrial fibrillation treatment with a fast-acting, effective and well tolerated first-line pharmacological therapy for acute cardioversion, alleviating the burdens of electrical cardioversion on patients, physicians and healthcare systems”, said Andrea Haegebarth, Ph.D., Global Head of Research and Early Development for Cardiovascular, Renal, Immunology at Bayer’s Pharmaceuticals Division. “We look forward to advancing the program through clinical development, which will strengthen Bayer’s cardiovascular portfolio and advance research efforts to the benefit of a broad patient population in need for novel and better medicines.”
The current gold standard to treat acute AFib episodes is electric cardioversion (ECV). This is an effective but resource-intensive and logistically challenging procedure, which is normally scheduled in advance and typically requires sedation or even anesthesia to safely deliver an electrical shock to the patient and restore the heart to its normal sinus rhythm. On the other hand, currently available anti-arrhythmic drugs (AADs), which are commonly used for the management of symptomatic AFib, can’t be applied to broad patient populations due to a number of contraindications (such as for patients with structural heart disease) and safety risks, including abnormal heart rhythms and sudden death. Additionally, they show limited, short-term efficacy, require close monitoring and bear the risk of serious side effects.
Investigational GIRK4 inhibitor (BAY 3670549) is derived from Bayer’s strategic research alliance with the Broad Institute.
AFib is one of the most common sustained cardiac rhythm disorders (arrhythmias). It results from rapid, disorganized electrical signals in the upper chambers (atria) of the heart, causing them to quiver and contract quickly and irregularly. As a result, the atria do not empty completely, and blood does not flow properly, causing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke.
The prevalence of AFib continues to increase globally. Projection studies show that the number of people with AFib will rise to 15.9 million in 2050 in America and 17.9 million in 2060 in Europe. People with AFib are 5 times more likely to suffer a stroke than people without AFib. AFib-related strokes are also associated with a 50% likelihood of death within one year.
