* Drug seen as safe, effective for extended use-researchers
* Recurrence or death 3.8 pct for low dose; 4.2 pct for high
* Rate for placebo group was 11.6 percent
* Major bleeding extremely low with apixaban in year-long study
By Bill Berkrot
Dec 8 A new blood clot preventer from Pfizer Inc and Bristol-Myers Squibb Co reduced the risk of recurrence of clots in veins and lungs and death by 80 percent with no increase in major bleeding in a study testing extended use of the drug.
In the year-long trial of 2,486 patients who had been previously treated for the condition known as venous thromboembolism (VTE) the drug, apixaban, met the combined primary goal by significantly reducing the recurrence of blood clots and death from any cause compared with a placebo, according to data presented at the American Society of Hematology (ASH) meeting in Atlanta, Georgia.
The rate of recurrence or death was 11.6 percent in the placebo group compared with 3.8 percent for those who got 2.5 milligrams of apixaban and 4.2 percent for the 5 mg dose of the drug. The results were also published in the New England Journal of Medicine.
The incidence of major bleeding, always a concern with blood thinners, was extremely low in all three arms of the trial, researchers said - 0.5 percent for placebo, 0.2 percent for the low dose of apixaban and 0.1 percent for the higher dose.
"Usually when you have an effective antithrombotic you have to pay a price in terms of bleeding. This was not the case in this study," Dr. Giancarlo Agnelli, the study's principal investigator, said in a telephone interview.
"There was no evidence at all of increased major bleeding and this is extremely important because you are comparing an active drug with placebo," he said.
There was a slightly higher rate of clinically relevant nonmajor bleeding, such as nose bleeds that required medical attention, observed in patients taking the higher dose of apixaban at 4.2 percent compared with the low dose and placebo, researchers said.
Apixaban belongs to a new class of blood thinners that aim to replace decades old and difficult to use warfarin. The drug, which will be sold under the brand name Eliquis, is widely considered to be one of the most important new medicines for Pfizer and Bristol-Myers, both of which saw their top selling products lose patent protection in the past year.
AWAITING U.S. APPROVAL
It is approved in Europe and awaiting a U.S. approval decision for preventing blood clots and strokes in patients with atrial fibrillation - a type of irregular heart beat - and is also being tested against warfarin as a primary treatment for VTE with data expected next year.
A rival drug from Bayer and Johnson & Johnson called Xarelto is already approved for both conditions, but based on clinical data analysts have said they believe Eliquis is the best class.
An approval for extended use in VTE patients, during which they would take the drug for at least a year after initial treatment, could significantly boost future sales.
"The evidence is for one year. The next step would be to see whether this clinical benefit is extended after one year," Agnelli said.
VTE consists of deep vein thrombosis, typically blood clots in the legs, and pulmonary embolism, which are dangerous clots in the lungs. Clots that begin in the extremities can travel to the heart and lungs and can be fatal. VTE is typically treated with warfarin for three to six months.
After that, "there is quite a remarkable level of uncertainty about whether to extend or not," explained Agnelli, professor of internal medicine at the University of Perugia in Italy, who presented the data at the ASH meeting.
"Extended treatment might be clinically relevant because the recurrence rate after stopping treatment can be 10 percent in the first year," Agnelli said. "Reducing the recurrence of VTE means reduced hospitalization costs and in some cases fewer fatal events."
Physicians have been looking for alternatives to warfarin, which must be closely monitored to keep levels therapeutic but not toxic. The new drugs do not require monitoring or the dietary and lifestyle changes necessary with warfarin. But they still face an uphill battle as warfarin is far less expensive, and doctors have a comfort level using a drug that has been around for more than half a century despite the challenges.
Patients in the study had received treatment with warfarin for six to 12 months before starting the one-year extension trial that aimed to show further treatment could reduce recurrence rates and to see if the lower dose of apixaban was a viable option.
" It is quite clear that the lower dose is as effective as the higher. For the first time we showed that by reducing the dose of an antithrombotic agent in this clinical setting we can have the same efficacy with no major bleeding," Agnelli said.
"This is actually something that could change clinical practice," he added.