Study: Bayer, Johnson & Johnson's Xarelto prevents blood clots, raises bleeding risk

Study results released Tuesday suggested that although Bayer and Johnson & Johnson's experimental drug Xarelto (rivaroxaban) worked as well as standard treatment of sanofi-aventis' Lovenox (enoxaparin) at preventing venous thromboembolism (VTE) in hospitalised patients, the agent was associated with higher bleeding rates. Commenting on the data, which were presented at the ACC annual meeting, lead author Alexander Cohen noted that "we did not see a consistently positive benefit-risk balance with [Xarelto] use, and thus further analysis is required to identify which groups of patients...may derive benefit from" VTE prevention with the oral anti-coagulant.

The MAGELLAN trial randomised 8100 patients with limited mobility because of acute medical illnesses to receive Xarelto for 35 days or Lovenox for 10 days, followed by placebo for the remainder of the study. Results demonstrated that after 10 days, 2.7 percent of patients in both groups had a VTE or died as a complication of one. After 35 days, 4.4 percent of patients who took Xarelto developed a VTE, compared with 5.7 percent of patients in the other group.

However, results indicated that after 10 days, bleeding that required medical care occurred in 2.8 percent of patients who received Xarelto, versus 1.2 percent of those taking Lovenox. Further, after 35 days, the bleeding risk was 4.1 percent with Xarelto, compared with 1.7 percent for the Lovenox group. Johnson & Johnson's vice president of cardiovascular development Peter DiBattiste said the company was now trying to identify patients who may be at higher risk for bleeding to help control the unwanted effects. "We have demonstrated efficacy and we want to understand better how the risks and benefits play out," he added.

DiBattiste noted that although the drugmaker had previously suggested it would seek approval of Xarelto for use in hospitalised patients based on the study results, the company would further analyse the new data before making final plans. However, Frank Misselwitz, head of Bayer’s cardiovascular unit, remarked that when the trial was designed three years ago, they considered it a "blue-sky scenario" to think all patients would require Xarelto, adding that "this was quite a realistic outcome that only certain patients would require it." He noted that the findings didn’t affect the company's forecast that the product will bring in more than 2 billion euros ($2.8 billion) in annual sales.

Xarelto has been on the market in Europe since its approval in 2008 for the prevention of venous blood clots in patients undergoing hip or knee replacement surgeries. In January, the companies said they had made regulatory filings in Europe and the US seeking approval of Xarelto for the prevention of stroke in patients with atrial fibrillation (AF), and Bayer also filed for European approval of the agent as a treatment for deep vein thrombosis (DVT), for the prevention of recurrent DVT and pulmonary embolism (PE). In addition, Johnson & Johnson filed its reply to an FDA complete response letter for further information on the drug for the prevention of DVT and PE in patients undergoing total hip or total knee replacement surgery.

Commenting on the MAGELLAN trial, Wells Fargo analyst Larry Biegelsen said the study had low expectations, partly because of the potential for higher bleeding rates seen with Xarelto. The analyst noted that the acute medically ill population represents a $1.2 billion to $1.8 billion market opportunity for Xarelto, although he didn't include these figures in his sales projections. Still, that analyst predicts that sales in the US could top $1.5 billion in 2015, assuming approval this year for AF and prevention of DVT.

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