Positive data from XENTION's XEN-D0103 phase 1 trial on AF

Mar 20 2012

XENTION LTD, the Cambridge-based biopharmaceutical company specialising in the discovery and development of ion channel-modulating drugs, reported positive data today from a phase 1 trial of XEN-D0103 administered orally. The drug, a selective inhibitor of the cardiac potassium channel Kv1.5, was well tolerated and demonstrated good pharmacokinetic (PK) properties. The results support the continuing development of XEN-D0103 for the treatment of atrial fibrillation (AF), a commonly encountered and potentially serious cardiac arrhythmia in which the atria of the heart beat in a rapid and irregular manner, resulting in reduced cardiac output and increased risk of stroke.

The phase 1 clinical trial, which was conducted in the UK, studied single and multiple ascending oral doses of XEN-D0103 in healthy volunteer subjects in three parts. The study evaluated the safety and pharmacokinetics of various doses and also the effects of food. XEN-D0103 was well tolerated with a good PK profile and no significant food, gender or age related effects were observed. No significant adverse events were reported.

Importantly, a detailed ECG (electrocardiogram) analysis of data collected from the first cohort of 30 healthy volunteers indicated that XEN-D0103 had no effect on the QTcF interval. This absence of any detectable effect on QTcF, confirming the atrial selectivity of XEN-D0103, is an important safety attribute for a new atrial fibrillation drug, since many current antiarrhythmic drugs can lead to significant QT-interval prolongation and further arrhythmia problems.

Tim Brears, Chief Executive Officer of Xention commented, "We are very pleased to report these positive phase 1 data, specifically the observations that XEN-D0103 may have a much safer profile than current antiarrhythmic drugs, many of which have significant side effects. The potential market for XEN-D0103 is significant with one in four adults over the age of 40 developing AF in their lifetimes and approximately three million patients suffering atrial-fibrillation-related strokes each year. We are now preparing for the initiation of phase 2 efficacy trial of XEN-D0103 in patients with atrial fibrillation".

XEN-D0103 is the lead product of Xention's portfolio of atrial fibrillation drugs. In addition to targeting Kv1.5, Xention is also conducting research on inhibition of the acetylcholine-activated potassium channel IKACh (Kir3.1/3.4) and highly potent and selective IKACh antagonists are currently under evaluation in preclinical models. The ion channels Kv1.5 and IKACh represent two of the most exciting targets for novel atrial fibrillation therapies, and Xention is at the forefront in developing effective drug modulators of these channels.