Bristol, Pfizer anti-clot drug hits goals in trial

New York, July 8: An experimental anti-clotting medicine from Bristol-Myers Squibb Co and Pfizer Inc met its main effectiveness and safety goals in a mid-stage study, researchers said today, positioning it as a future option over current popular but problematic drugs.

Patients treated with apixaban, a pill, had comparable rates in two main measures to those on the standard of care, an injected therapy plus one drug from the class that includes the widely used warfarin. The measures included rates of blood clots and dangerous bleedings.

Though effective at alleviating clotting, many anticoagulant therapies come with serious drawbacks. Heparin drugs must be injected or given intravenously, and warfarin is notoriously difficult to regulate properly because of its interactions with food and other medicines.

Apixaban, meanwhile, is an oral drug that does not need regular monitoring or dose adjustments, making it a ''great alternative,'' said Dr Harry Buller, lead investigator on the study and chairman of the department of vascular medicine at the Academic Medical Center in Amsterdam.

''The search for new anticoagulants is not so much to beat them in terms of efficacy,'' Buller said. The reason for ''the whole explosion of anti-thrombotic agents (is) to make life easier for these patients,'' he said.

Buller was presenting the study's results today at the International Society on Thrombosis and Haemostasis meeting in Geneva.

Late-stage trials are already underway for apixaban, and the companies plan to file for US approval in the second half of 2009.

Apixaban is one of several pills being developed by drug makers that block the Factor Xa protein, which plays an early role in the chemical process leading to blood clots.

Researchers hope they also can be used by patients with atrial fibrillation, or irregular heartbeat, to prevent stroke.

Late-stage data on another Factor Xa drug from Bayer AG were set to be presented at the meeting today.

'DISASTER WITH EXANTA'

Excitement over Factor Xa drugs follows the downfall of Exanta, a once-promising anticoagulant from AstraZeneca Plc that had been associated with liver toxicity. Exanta blocked another clotting protein called thrombin.

''After the disaster with Exanta, people are really looking for new anticoagulants to fill that gap and to replace warfarin, and I think this step ... is very pleasant to see,'' Buller said of the apixaban clinical trial.

The 12-week Phase two study involved 520 patients who suffered a deep vein thrombosis, which is a clot that forms most frequently deep inside the leg.

There were three apixaban treatment groups: patients on five milligrams of the experimental drug twice a day; 10 mg twice a day; or 20 mg once a day. A fourth control group received an injectable anticoagulant plus warfarin or a similar drug.

The main efficacy measure involved the combined rate of incidents, including a new deep vein thrombosis or lack of improvement in the original DVT, and blood clots that progress to the lungs known as pulmonary emboli.

Rates of the incidents were 6 per cent for patients on 5 mg of apixaban, 5.6 per cent for the 10 mg, and 2.6 per cent for the 20 mg. The rate was 4.2 per cent for the control group. Buller said differences among treatment groups were not clinically relevant.

The main safety measure examined bleedings, the rates of which were 8.6 per cent for the 5 mg apixaban group, 4.5 per cent for the 10 mg, 7.3 per cent for the 20 mg, and 7.9 per cent for the control group. These differences were not clinically relevant either, Buller said.

There were no adverse events, including no sign of liver toxicity, he said.

Bristol-Myers and Pfizer agreed in April to develop and sell apixaban together. They are currently running two Phase 3 apixaban trials: one to prevent blood clots among surgical patients or those whose illness puts them at risk; a second to prevent stroke for patients with atrial fibrillation.

REUTERS >