Xarelto in long-term clot prevention study

Bayer has launched a trial of its anticoagulant Xarelto in long-term, secondary prevention of blood clots.

The EINSTEIN CHOICE study will investigate Xarelto (rivaroxaban) 10 mg and 20 mg once daily for the long-term, secondary prevention of venous blood clots following acute deep vein thrombosis (DVT) and pulmonary embolism (PE).

If Bayer and its US marketing partner Johnson & Johnson can prove the value of Xarelto in long-term use in these patients, it could help it extend its lead over rival novel anticoagulants, and expand its market.

But Xarelto and its rivals – Boehringer Ingelheim's Pradaxa and Pfizer and BMS' Eliquis - are coming up against resistance from doctors reluctant to use these new oral agents instead of the tried-and-tested treatments, warfarin and aspirin. One reason for this is their high cost, but another is a number of safety concerns, including bleeding risk.

Boehringer's Pradaxa is currently suffering under suspicion of its bleeding risk, including an FDA review, plus thousands of US lawsuits alleging links to severe or fatal bleeding. Bayer and J&J are keen to exploit this weakness and demonstrate a strong safety profile for Xarelto. Bayer and J&J's drug has also suffered its own setbacks, however – in January an FDA committee voted unanimously to reject Xarelto as a treatment for acute coronary syndrome (ACS), saying the data presented was inadequate.

One of the aims of the new Xarelto trial is to see if a lower 10mg dose can provide all the protective benefits of a higher 20 mg dose, but with lower risk of bleeding.

An earlier trial of Xarelto at 20 mg once daily suggested a significant reduction in symptomatic DVT and PE in patients who previously completed 6 or 12 months of anticoagulation treatment. EINSTEIN CHOICE will include around 2,850 patients across the globe, comparing Xarelto at doses of 10 mg or 20 mg to aspirin at 100 mg in patients who have already taken anticoagulants for 6-12 months.

"If anticoagulant therapy is stopped after 6 to 12 months in patients with unprovoked venous thromboembolism, the risk of recurrence is about 10% at one year. Nonetheless, many physicians stop warfarin treatment after six months and may switch patients to aspirin because of the inconvenience of warfarin management and fears about the risk of bleeding," said Jeffrey Weitz, Professor and Deputy Chair Research, Department of Medicine, McMaster University, and Executive Director of the Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada and Co-Chair of the EINSTEIN CHOICE Steering Committee

Bayer and J&J are working on another way of enhancing safety – developing an antidote to reverse the effect of the drug, working with a firm called Portola, which has a candidate in currently phase 2.

Links

Resounding FDA 'no' for new Xarelto indication