Yesterday, Bristol Myers Squibb and Pfizer agreed to stop AVERROES, a late-stage clinical trial of an experimental blood thinner, early. It’s relatively rare for a trial to be stopped for positive reasons, but that is what happened here. An independent analysis concluded that the blood thinner, called apixaban, was more effective than aspirin at reducing strokes and blood clots anywhere outside of the brain in patients with atrial fibrillation, a common abnormal heart rhythm. Stroke is a major complication for patients that have this heart problem, and drug companies would like to find a more manageable way to reduce patients’ chances of having one.
Apixaban is one of a slew of potential new blood thinners in the pipeline that is an oral inhibitor of Factor Xa, a protease enzyme that sits at a key point in the body’s complicated blood coagulation cascade. Matthew Herper at Forbes recently broke down how another drug in this same class, Merck’s betrixaban, works.
One thing to keep in mind is that none of the 5600 patients in this study were taking warfarin, a decades-old blood thinner that’s still one of the gold standards for preventing stroke. For patients with atrial fibrillation, warfarin, a vitamin K antagonist that interferes with the coagulation cascade, is generally considered to be a more effective option than aspirin, which prevents blood platelet activation.
The patients in the AVERROES trial, BMS’s press release explains, were either unable to take or chose not to take warfarin. I can understand the perspective of the folks choosing not to go that route. Warfarin works, it’s cheap, and it’s also an oral medication, but it’s far from perfect. People who take it must be very carefully monitored by a physician, because other drugs and even foods in the diet can alter its effects in the body. And with blood thinners, you’re always walking a tightrope- too high a dose can lead to excessive bleeding. Also, some genetic differences can affect how well warfarin will work. Patients who have that genetic makeup might want to have another option that they can take in the form of a pill.
But apixaban is still an investigational agent- FDA has yet to approve it. The news in this trial was good news, but given the relative effectiveness of aspirin I’m not sure how surprising it really was to those following this field closely. To get a complete picture of what apixaban can do, it will be good to see what comes of the ongoing ARISTOTLE trial. That trial, like AVERROES, is a Phase III, randomized, double blind clinical trial in patients with atrial fibrillation. But instead of pitting apixaban against aspirin, it pits apixaban against warfarin. Stay tuned.
Leave a Reply