J&J, Bayer Aim to Expand Xarelto's Uses

Johnson & Johnson and Bayer AG announced plans Friday to launch clinical trials of the anticoagulant Xarelto against three new diseases in an ambitious bid to widen the market for a drug poised to exceed $1 billion in sales this year.

The initiative includes two studies to test the anticlotting agent in patients with acute coronary syndrome, a condition marked by unstable chest pain that often leads to a heart attack and accounts for 1.1 million hospital admissions annually in the U.S.

A previous major study of that condition yielded positive results, but the U.S. Food and Drug Administration has rejected three bids by the companies to approve Xarelto for ACS-related uses, most recently last March. The agency acted after advisory panels said flaws in the data left them uncertain about risks and benefits.

The companies are devising a new trial design in hopes of making a better case to the FDA. Xarelto is approved for ACS in 40 countries in Europe, Latin America and Asia.

The other two diseases being studied are stroke caused by a clot of unknown origin and peripheral artery disease, the accumulation of fatty deposits that can obstruct blood flow in the legs. Together with eight other Xarelto studies the companies have launched since March 2013, the findings could lead to a doubling to at least 12 as the number of approved indications for the drug.

That would enable J&J and Bayer to press their advantage in a burgeoning market for a new generation of anticlotting agents that have come on the market since 2010. Sales of Xarelto are currently outpacing rivals Pradaxa from Boehringer-Ingelheim GmbH and Eliquis from Pfizer Inc. and Bristol-Myers Squibb Co. in what analysts widely expect to be a multibillion-dollar category.

The companies announced the new studies in Barcelona in advance of the annual European Society of Cardiology Congress, which opens there Saturday.

"Blood clot formation represents a huge patient burden that goes across multiple different diseases," said Paul Burton, cardiovascular therapeutic area lead at J&J. "Many of these folks don't have any options."

Xarelto and its rivals are already approved in the U.S. and many global markets for such indications as stroke prevention in patients with atrial fibrillation and treatment and prevention of blood-clot related conditions called deep vein thrombosis and pulmonary embolism.

For patients with ACS or whose heart disease has been treated with a metal device called a stent, long-standing practice is to give aspirin and another drug such as clopidogrel, both of which inhibit the ability of blood platelets to clump together to form clots.

This "dual antiplatelet" strategy is effective, but still leaves a significant portion of patients at long-term risk of a subsequent heart attack or other serious outcome, said C. Michael Gibson, a Harvard cardiologist expected to have a key role in the studies.

Xarelto blocks generation of an enzyme called thrombin, another crucial contributor to clot formation that Dr. Gibson described as a "net that holds the clot together." Thrombin is "chronically turned up" in patients with ACS, he said, but current therapy does nothing to block it.

In the earlier Xarelto ACS study, the drug was added to the two-pronged attack on platelets. Heart attacks and other serious events were reduced but at an increased risk of major bleeding episodes.

The new ACS studies will combine Xarelto with just one antiplatelet drug in hopes of maintaining the benefit against heart attacks while reducing the bleeding risk.

"We believe that inhibiting both pathways is perhaps a better strategy than doubling up on the platelet," Dr. Gibson said.

J&J said which antiplatelet drug will be eliminated is still being determined. But dropping aspirin from the regimen is a logical option since it carries an increased bleeding risk in the stomach and intestinal track unrelated to cardiovascular disease.

The companies plan to conduct an initial study of up to 3,000 patients. If the data are positive, they would mount a second trial of more than 15,000 patients to determine the long-term effect of the regimen on serious heart events and bleeding risk.

Write to Ron Winslow at [e-mail]

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