The race to get a new class of oral anticoagulants onto the market may be being led by Bayer and Johnson & Johnson’s rivaroxaban but Bristol-Myers Squibb and Pfizer’s apixaban may not be too far behind.
B-MS has just presented positive Phase II data at the International Society on Thrombosis and Haemostasis meeting in Geneva for apixaban, a new, direct-acting inhibitor of coagulation Factor Xa, which was evaluated in patients with confirmed deep vein thrombosis. 520 patients were allocated into one of three groups – apixaban 5mg and 10mg twice a day or 20 mg once-daily – while a fourth control group received low molecular weight heparin or fondaparinux followed by an open-label vitamin K antagonist such as warfarin.
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 (pulmonary emboli). Rates of the incidents were 6% for patients on 5mg of apixaban, 5.6% for 10mg and 2.6% for the 20 mg. The rate was 4.2% for the control group and Harry Buller, lead investigator on the study and chairman of the department of vascular medicine at the Academic Medical Center in Amsterdam, said the differences among treatment groups were not clinically relevant.
The safety measure examined bleedings and the rates were 8.6% for the 5mg apixaban group, 4.5% for 10mg, 7.3% for 20 mg and 7.9% for the control group. These differences were not clinically relevant either, Dr Buller noted, adding that there were no adverse events, including no sign of liver toxicity. He went on to state that the drug can be given as the sole treatment in a fixed dose and “appears to be a very attractive alternative to standard therapy in patients with DVT”.
Though effective at alleviating clotting, many anticoagulants come with serious drawbacks as heparin drugs have to be injected or given intravenously, while warfarin is notoriously difficult to regulate. However, apixaban is an oral drug that does not need regular monitoring or dose adjustments and is one of the new anticoagulants, like Xarelto (rivaroxaban), that hope to avoid the problems that AstraZeneca’s clotbuster Exanta (ximelagatran) suffered last year. It was withdrawn from the global market after patient safety data threw up a single case of serious liver injury.
B-MS spokesman Jeffrey Macdonald told PharmaTimes World News that Phase III trials are now underway for apixaban, for preventing venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. The company, which signed a development deal worth up to $1 billion for the drug with Pfizer in April, plan to file for US approval in the second half of 2009.
Bayer may file rivaroxaban at the end of this year and believes its once-a-day dose could give an advantage over apixaban, which will likely be given twice a day and Mr Macdonald would not comment on whether being second to market is a major problem for B-MS. He added that the firm is concentrating for the moment on clinical matters and believes that there is a large market for apixaban.