CAMBRIDGE, U.K.—Xention Ltd., a Cambridge-based biopharmaceutical company specializing in the discovery and development of ion channel-modulating anti-arrhythmic drugs, recently announced that the Phase 2 development of its lead atrial fibrillation (AF) program is underway.
In 2013, Xention entered into an agreement with Servier for the development and commercialization of XEN-D0103, reportedly a potent and selective oral modulator of the cardiac potassium channel Kv1.5, which was discovered and developed by Xention for the treatment of AF. Under the terms of the agreement, U.S. and Japanese rights to XEN-D0103 have been retained by Xention, while Servier has commercialization rights in all other territories of the world. Servier and Xention are undertaking a joint program of clinical development for XEN-D0103, including two Phase 2 clinical studies aimed at demonstrating the efficacy of the compound in AF.
The first of the planned Phase 2 studies (the XAPAF study) is being managed by Xention and is designed to assess the efficacy and safety of XEN-D0103 in patients with paroxysmal AF. The study is being undertaken at Eastbourne General Hospital, with Dr. Neil Sulke as principal investigator. The design is a double-blind, randomized, placebo-controlled, crossover trial in a total of 20 patients suffering from paroxysmal AF who also have implanted pacemakers, enabling continuous beat-to-beat monitoring of drug efficacy. Commenting on the study, Sulke said, “‘XEN-D0103 is a potent and selective blocker of the potassium channel Kv1.5, and this is the first time a highly selective Kv1.5 blocker is being assessed in patients with AF.”
“We are delighted to report that our partnership with Servier is progressing extremely well and that XEN-D0103 is being evaluated in the first of two planned studies in AF,” said Tim Brears, CEO of Xention.
As for that other study, Dr. Isabelle Tupinon-Mathieu, vice president of research and development and head of cardiovascular and metabolism therapeutic innovation at Servier, said: “We are pleased to announce that the second study, DIAGRAF-IKur, managed by Servier, is in the process of being approved by the competent authorities and should start in the near future.”
In addition to its Kv1.5 program, Xention is also developing antagonists of Kir3.1/3.4 (IKACh), a second promising target for AF. Both Kv1.5 and Kir3.1/3.4 (IKACh) are expressed only in the atria and represent what the companies call “exciting” targets for the development of atrial-selective therapeutics for the treatment of AF.
As noted by Xention, AF is the most common sustained cardiac rhythm disturbance, occurring in between 1 percent and 2 percent of the general population but increasing rapidly with age. It is estimated that more than six million Europeans suffer from this arrhythmia, and its prevalence is calculated to increase by more than twofold in the next 50 years as the population ages. AF confers a fivefold increased risk of stroke, and one in five of all strokes are attributable to AF. The ischemic strokes seen in association with the arrhythmia are often fatal, and those that survive are often left crippled by their stroke and likely to suffer recurrent strokes. Around 1 percent of the healthcare budget of Western European and North American countries is spent on the management of AF. “Thus,” Xention says, “this disease presents a rapidly growing social, medical and public health problem in need of urgent solution.”