Wyeth and Zealand seek to still irregular beating heart

Wyeth has begun first-in-man trials for an oral drug designed to calm an irregular heart beat, triggering a milestone payment to its partner on the project, Denmark-based Zealand Pharma.

ZP1609 (GAP-134) is the first ever first orally available 'gap junction modifier' and has shown pharmacological effects in animal models of both ventricular and atrial arrhythmias.

The drug is the second compound to enter clinical trials from an extensive collaboration on gap junction modifiers.

The other, rotigaptide (ZP123) is currently in Phase II trials and, according to Zealand, is expected to be the first drug that specifically modifies this target.

An irregular heart beat, caused when the ventricle chamber of the heart loses their coordinated beat, can be life-threatening.

Patients who suffer from an acute heart attack (myocardial infarction), have a particularly high risk of developing ventricular arrhythmia and the companies envisage their products being given to these patients to try and prevent the onset of arrhythmia.

Gap-junctions are specialised pores that ensure the coordinated transmission of electrical impulses from cell-to-cell, which is essential for synchronised contraction.

This spreading of electrical impulses is scrambled following a heart attack and these drugs attempt to correct that by modifying gap-junction communication.

Zealand Pharma entered into a development and license agreement with Wyeth in 2003 to co-develop gap junction modifiers for the treatment of cardiovascular diseases.

In 2004, the collaboration was expanded by an R&D agreement, and in 2005, a third agreement between the two companies was signed.

Under the 2005 agreement, Zealand granted Wyeth rights to the unique Zealand compound library for novel compounds with potential gap junction modifying properties.

It was from this library that the two companies identified ZP1609, a small modified dipeptide.

Zealand specialises in taking peptides and then adjusting them to increase their persistence in the human body through preventing enzymatic digestion and also enable them to be used in tablet form.

GlaxoSmithKline (GSK) was developing a gap junction blocker for epilepsy, migraine and neuropathic pain (simply called 406725), but the project seems to have been scrapped as it is no longer appears on the pharma heavyweight's pipeline.