Real-World XALIA Data Confirm Safety and Efficacy Profile of Xarelto for DVT

December 7, 2015—Janssen Pharmaceuticals, Inc. and its development partner, Bayer HealthCare, announced the presentation and publication of results from their real-world XALIA study showing that, in people with deep vein thrombosis (DVT), the rates of major bleeding and recurrent blood clots for the companies’ Xarelto (rivaroxaban) in routine clinical practice were generally consistent with those observed in phase 3 research. Patients taking Xarelto also had shorter lengths of hospital stays than those given standard anticoagulation. 

The prospective study was presented at the 2015 American Society of Hematology (ASH) annual meeting and simultaneously published online ahead of print by Walter Ageno, MD, et al in The Lancet Hematology. The ASH 2015 meeting convened December 5–8 in Orlando, Florida.

In the companies’ announcement, XALIA Principal Investigator Prof. Alexander G. G. Turpie, MD, commented, “On average, every 37 seconds someone in the Western world dies from a venous blood clot, so it is important we understand the effectiveness and safety of available treatment options for these potentially life-threatening blood clots. The real-world insights from XALIA confirm the positive benefit-risk profile of rivaroxaban for the treatment of DVT that was observed in the phase 3 EINSTEIN-DVT study, signaling that the medicine is performing as expected in patients that physicians typically see in everyday clinical practice." Prof. Turpie is from McMaster University and Hamilton Health Sciences in Hamilton, Ontario.

Sponsored by Janssen and Bayer HealthCare, XALIA (XA inhibition with rivaroxaban for long-term and initial anticoagulation in venous thromboembolism) was a phase 4, prospective, noninterventional, observational study of patients with DVT, or DVT with concomitant pulmonary embolism (PE), treated with Xarelto or standard anticoagulation. Standard anticoagulation was considered initial treatment with heparin, low-molecular-weight heparin, or fondaparinux, typically overlapping with and followed by warfarin.

According to the companies, the study evaluated the safety and effectiveness of Xarelto, taken once daily, for the treatment of DVT in routine clinical practice as compared to standard anticoagulation. The primary outcome was the incidence of adverse events (major bleeding, recurrent blood clots, and all-cause mortality). Healthcare resource utilization, including length of stay, was also evaluated. A propensity score analysis was completed to address differences in baseline characteristics and help correct any selection bias. 

The XALIA investigators enrolled a total of 5,142 patients, ≥ 18 years of age, in 21 European countries. Of these patients, 4,768 were included in the primary analysis. For the propensity score analysis, which was prespecified in the protocol, 4,515 patients were included (2,505 in the Xarelto group and 2,010 in the standard anticoagulation group). Patients were enrolled between June 2012 and March 2014 and followed for at least 12 months. The study was requested by the European Medicines Agency (EMA), with the protocol developed with and approved by the EMA, noted the companies.

Key XALIA findings (from the propensity score analysis) included the following for Xarelto versus standard anticoagulation: 

•    Major bleeding, 0.8% versus 2.1% (hazard ratio [HR], 0.77; confidence interval [CI], 0.4–1.5; P = .44). There were no fatal bleeding events in the Xarelto group; two fatal bleeding events occurred in the standard anticoagulation group. In EINSTEIN-DVT, major bleeding occurred in 0.8% of patients taking Xarelto and there was one fatal bleeding event.

•    Recurrent blood clots, 1.4% versus 2.3% (HR, 0.91; CI, 0.54–1.54; P = .72). In EINSTEIN-DVT, recurrent blood clots occurred in 2.1% of patients taking Xarelto.

•    All-cause mortality, 0.4% versus 3.4% (HR, 0.51; CI, 0.24–1.07; P = .07). In EINSTEIN-DVT, all-cause mortality occurred in 2.2% of patients taking Xarelto.

As hospitalization for blood clots remains a major health care cost, the study also examined hospital admissions and found them to be shorter in duration for patients treated with Xarelto, compared to those receiving standard anticoagulation with mean length of hospital stay of 5 versus 7.7 days (geometric means ratio, 0.66; CI, 0.61–0.72).

The companies advised that methodological and other differences between the studies limit the ability to directly compare results of XALIA to the pivotal phase 3 study EINSTEIN-DVT, which was used by regulatory authorities worldwide to approve Xarelto. EINSTEIN-DVT was published in The New England Journal of Medicine (2010;363:2499-2510).

In November 2012, Janssen announced that the US Food and Drug Administration approved the new indications for Xarelto for the treatment of DVT and/or PE, and to reduce the risk of recurrence of DVT and PE following initial treatment.