Case Study 1: Next-Generation Oral Anticoagulants

Oral anticoagulants (blood thinners) are widely used to prevent and treat venous thrombosis (blood clots in the legs) and to prevent strokes in people with a common rhythm disturbance of the heart called atrial fibrillation.  Indeed, in our aging population, atrial fibrillation has emerged as one of the most common chronic heart conditions that frequently leads to strokes and heart failure.  For decades, the gold-standard oral anticoagulant has been warfarin (often marketed under the brand name Coumadin).  Warfarin is cheap, effective and, if used correctly, safe.  So why is there interest in a next-generation drug?  The problem with warfarin is that its correct administration presents a huge burden to the patient.  Warfarin interacts with a very long list of other drugs commonly prescribed to older patients, including antibiotics, statins, and non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen), as well as many herbs and even foods.  This makes frequent monitoring of bleeding times vital, with frequent dose adjustments.  If this is not done correctly, patients are at risk of blood clots and strokes (blood "too thick") or bleeding and haemorrhages (blood "too thin").

For these reasons, there has been a large discovery and development effort in the pharma industry to develop 2nd-generation oral anticoagulants that can replace warfarin.  These drugs interact with the same or similar targets in the coagulation pathway as warfarin, but have completely different chemical structures.  Just as AngioDesign is doing with the design of its next-generation ACE inhibitors, the design of these next-generation oral anticoagulants was in many cases achieved through rational drug design.  These development efforts have borne fruit, and in recent years several next-generation oral anticoagulants have come onto the market (e.g. dabigatran, rivaroxaban, apixaban, and edoxaban) and are rapidly taking market share from the gold-standard drug, warfarin.  These newer drugs have been shown to be as effective as warfarin, and in some cases more effective, but have significant advantages in terms of ease of use and safety and are quickly becoming blockbusters.  Therefore, despite the fact that warfarin is a cheap generic with decades of experience in the clinic, the 2nd-generation oral anticoagulants are changing clinical practice because of clear advantages in convenience and safety (Stambler, 2013; Cheng & Barillari, 2014).