With a new indication in preventing venous thromboembolism, Johnson & Johnson and Bayer AG appear to be succeeding with their goal of positioning their once-daily Factor Xa inhibitor Xarelto (rivaroxaban) to have the broadest label of the novel oral anticoagulants.

[Editor’s Note: This article was updated to correct the generic name of Xarelto to rivaroxaban.]

In addition to stroke prevention in atrial fibrillation, novel anticoagulants have been positioned for a range of indications related to venous thromboembolism. This includes deep vein thrombosis, which in turn can cause pulmonary embolism and cut off the blood supply to the lungs.

Xarelto competes with Boehringer Ingelheim GMBH’s first-to-market direct thrombin inhibitor Pradaxa (dabigatran) and Bristol-Myers Squibb Co./Pfizer Inc.’s Factor Xa inhibitor Eliquis (apixaban); both drugs are taken twice daily.

J&J/Bayer have been looking to differentiate Xarelto as a drug that would be used across indications and medical specialties Also see "Janssen Looks To Differentiate Anticoagulant Xarelto With Broad Label" - Pink Sheet, 2 April, 2012..

On Nov. 20, Xarelto drug became the first novel oral anticoagulant cleared to treat deep vein thrombosis and pulmonary embolism and reduce the risk of recurrent DVT and PE events. The label expansion followed positive results in the EINSTEIN program presented at the American College of Cardiology meeting in March, which indicated similar efficacy against warfarin but a better safety profile. Xarelto had become the only novel oral anticoagulant approved for this indication in Europe in December 2011. The drug’s first approval was in Europe in October 2008, for VTE prevention after surgery (see chart).

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Bayer reported third quarter global Xarelto sales of €81 million ($103 million).

“Given the positive developments during the first nine months, we’re confident of exceeding our original sales target of €250 million to €270 million for the full year of 2012,” Marijn Dekkers, chairman of the management board, said during a third-quarter earnings call.

Xarelto has gained acceptance in the market despite competition with Pradaxa, a drug that has proven superior efficacy for stroke reduction. This is due to a number of reasons, including Xarelto’s once-daily dosing and variety of indications. And the downsides of Pradaxa have played a role, notably the increased risk of GI bleeding flagged in Pradaxa labeling and the non-significant myocardial infarction increase, said Decision Resources analyst Eamonn O’Connor (see related story, Also see "Eliquis Poised To Wake Up U.S. Oral Anticoagulant Market" - Pink Sheet, 24 December, 2012.).

Every year, some 900,000 people have a VTE episode in the U.S. and ease of administration could put Xarelto in a good position compared to the cumbersome injectable standard of care, which involves five to ten days of treatment with Sanofi’s now-generic low-weight molecular heparin Lovenox (enoxaparin), followed by three to six months of therapy with a vitamin K antagonist such as warfarin. For this indication, Xarelto is taken twice daily for 21 days, followed by once-daily dosing for the rest of the treatment period. In pivotal trials the mean treatment duration was about 200 days.

Other companies are testing novel anticoagulants in this indication, but Xarelto is the first to market Also see "Janssen Looks To Differentiate Anticoagulant Xarelto With Broad Label" - Pink Sheet, 2 April, 2012..

In a Nov. 5 note on Johnson & Johnson, UBS Investment analyst Rajeev Jashnani observed that the indication provides a nice market opportunity for Xarelto, with 150 million to 200 million warfarin doses administered annually.

Xarelto also is being positioned for an indication in reducing risk of cardiovascular events in patients with acute coronary syndromes, which includes acute conditions such as chest pain associated with heart attack, But the filing was subject to a “complete response” letter in June, due to missing data in the supporting ATLAS trial Also see "Xarelto Label Expansion Plans Slowed By FDA “Complete Response” On ACS Claim" - Pink Sheet, 22 June, 2012..

Xarelto’s broader label spanning atrial fibrillation, DVT/PE and possibly acute coronary syndrome “should help sustain growth despite competition from Eliquis, which has shown a compelling profile in a-fib,” Jashnani wrote.

Eliquis Also In Position For New VTE Indication

In general, physicians gain comfort with a drug that is approved for a broad range of indications, commented O’Connor, but once approved, Eliquis is nevertheless expected to dominate the market for preventing stroke in atrial fibrillation, based on the data showing it is safer and more efficacious for preventing events than warfarin.

Eliquis is also in development for VTE treatment and long-term prevention. At the recent American Society of Hematology meeting, Pfizer and Bristol reported positive results from the AMPLIFY-EXT trial in this setting ([A#14121206004]). The study design was unusual compared to trials of other novel anticoagulants in that two doses were tested and compared – 2.5 mg and 5 mg twice daily. Both doses proved to be highly effective for preventing events and bleeding rates were similar to placebo.

Flexibility in dosing could provide a competitive advantage. Bristol’s Jack Lawrence, who headed Eliquis development, said that the results from AMPLIFY-EXT reinforce the companies’ decision to dose the drug twice a day. Following the ARISTOTLE study, in which the drug showed significantly less bleeding compared to warfarin, it provides another example of a very favorable balance of efficacy and safety, he said.

A second VTE study, AMPLIFY, is ongoing. The companies declined to comment on timing for a filing pending the outcome of this trial.

Xarelto Takes Lead In Exploiting VTE Market Opportunity

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