J&J's Xarelto Approved for 8th Indication, Venous Thromboembolism

The U.S. Food and Drug Administration (FDA) approved Janssen Pharmaceutical's Xarelto (rivaroxaban) for the prevention of venous thromboembolism (VTE), or blood clots, in acutely sick patients in hospitals who are at risk for blood clots but who are not at high risk of bleeding.

This is the eighth U.S. indication for Xarelto. Six of those indications are for the treatment, prevention and reduction in the risk of VTE recurrence in a range of patient populations.

“Acute medical illness” is a term used to describe serious but common medical conditions. About seven million in the U.S. are hospitalized annually with diagnoses that fall within this broad term. They are at increased risk of blood clots, and that risk extends for up to three months after leaving the hospital. In fact, about 80% of these blood clots happen within the six weeks after being discharged.

Current medical guidelines recommend that acutely ill medical patients who are at risk of VTE be given anticoagulants, usually injectable drugs, while still in the hospital. But, routine use of coagulants outside the hospital is not recommended.

“Preventing blood clots is a critical priority for physicians treating patients with acute medical illnesses, which is why Janssen is pleased that the FDA approved the use of Xarelto to address this often fatal, yet preventable condition,” said James List, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development. “Rather than facing daily injections with older anticoagulants, patients now have a new oral treatment option that will help prevent blood clots, both in the hospital and after hospital discharge.”

These results are part of an extensive clinical trial program of Xarelto. The Phase III clinical program includes the MAGELLAN and MARINER trials. MAGELLAN data was published in 2013, which looked at Xarelto in preventing VTE in hospitalized patients with acute medical illness and restricted mobility. This trial began with the patients’ hospital stay and continued through post-hospital discharge. That trial met two co-primary efficacy endpoints, with Xarelto showing non-inferiority to enoxaparin, a heparin formulation.

The company then ran a post-hoc analysis of MAGELLAN with five more criteria that excluded patients who were at high risk for bleeding because of active gastroduodenal ulcer, recent bleeding, active cancer, severe bronchiectasis or pulmonary cavitation, or dual antiplatelet therapy. This established a promising benefit-risk profile for VTE prevention with Xarelto.

The Phase III MARINER trial was similar, and the data was published in 2018, with the focus on prevention of VTE or VTE-related death after hospital discharge. Xarelto did not decrease the composite endpoint of VTE and VTE-related death, but it did significantly decrease symptoms of VTE with a good safety profile.

Both of these trials are part of the EXPLORER clinical research program for Xarelto. EXPLORER is a collaborative program between Janssen and Bayer. By the time EXPLORER finished more than 275,000 patients had participated.

“With this new approval, Xarelto as an oral-only option now has the potential to change how acutely ill medical patients are managed for the prevention of blood clots, both in the hospital and for an extended period after discharge,” said Alex C. Spyropoulos, Professor of Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health at Lenox Hills Hospital, New York, New York. “The Phase III clinical studies in this high-risk patient group show us that Xarelto at the 10mg dose is an effective and safe option to help prevent blood clots.”

In the first quarter of 2019, Xarelto brought in $542 million, which was a drop of 6%. J&J indicated at the time that the decline was caused by more discounts for Medicare patients by up to 70%.