Stockholm, SE (August 31, 2010) — Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), announced today that the investigational, oral anticoagulant rivaroxaban successfully demonstrated non-inferiority compared to the standard of care1 for the prevention of recurrent venous thromboembolism (VTE) in patients with acute symptomatic deep vein thrombosis (DVT), with a comparable safety profile. Data from the pivotal Phase 3 EINSTEIN-DVT clinical trial were presented today during a Hot Line session at the European Society of Cardiology (ESC) Congress in Stockholm, Sweden.
“Results from EINSTEIN-DVT could transform the way physicians treat deep vein thrombosis,” said lead investigator Harry R. Büller, M.D., Academic Medical Center in Amsterdam, Netherlands, who presented the results. "While the current standard of care is effective when well-controlled, it is often associated with significant drawbacks for patients and physicians. A novel single-drug approach such as oral rivaroxaban could potentially provide an effective and well-tolerated, simple, fixed-dose regimen for the treatment of deep vein thrombosis as a replacement for current standard therapy."
In the study, oral rivaroxaban demonstrated non-inferiority for the primary efficacy outcome, defined as the cumulative incidence of symptomatic recurrent DVT and non-fatal or fatal PE, in patients with acute symptomatic DVT compared with the current standard of care of enoxaparin followed by a vitamin K antagonist (VKA)1, [2.1% vs. 3.0%, respectively (p <0.0001 for non-inferiority)]. Rivaroxaban also demonstrated similar results compared to the standard of care for the principal safety outcome measuring a composite of major and non-major clinically relevant bleeding events2,3 [8.1% in both treatment groups, (p=0.77)]. Treatment emergent cardiovascular-related outcomes4 were low in both treatment groups (0.7% vs. 0.8% in the rivaroxaban and enoxaparin/VKA arms, respectively), and there was no signal of serious liver injury observed in either group. Rivaroxaban was well tolerated in the study, and discontinuation rates related to adverse events were low and similar in both treatment groups.
This is the sixth Phase 3 trial in the ongoing rivaroxaban global development program that has demonstrated either non-inferiority (EINSTEIN-DVT) or superiority (RECORD 1-45, 6, 7, 8 and EINSTEIN-EXTENSION9).
According to research reported in the journal Circulation, approximately two million Americans have a DVT episode each year10. DVT may have burdensome and costly consequences such as pulmonary embolism, venous hypertension, ulceration, an increased risk of recurring clots and post-thrombotic syndrome.
About EINSTEIN Program
EINSTEIN is a global program of three Phase 3 clinical trials evaluating the safety and efficacy of rivaroxaban in the treatment and/or prevention of a recurrent, symptomatic VTE in patients with acute symptomatic DVT or PE, with a planned total enrollment of almost 9,000 patients.
The multinational EINSTEIN-DVT study compared the safety and efficacy of oral rivaroxaban – administered at 15 mg twice-daily for three weeks followed by 20 mg once-daily – with standard therapy [overlap therapy with enoxaparin and vitamin K antagonist (VKA)1]. More than 3,400 patients with acute symptomatic DVT in the deep veins of the knee or thigh, but without any symptoms of PE, were enrolled and received treatment for three, six or 12 months of therapy.
EINSTEIN-EXT evaluated 1,197 patients who had previously completed six to 12 months of treatment with a VKA for an acute episode of VTE (the collective term for DVT and PE) or have participated in the Phase 3 EINSTEIN-DVT or EINSTEIN-PE trials, in which they were treated with either rivaroxaban or a VKA, for the same time duration. Upon enrolling in EINSTEIN-EXT, patients were randomized to receive either 20 mg of rivaroxaban dosed once-daily or placebo and were evaluated for an additional six or 12 months. Results from EINSTEIN-EXT were presented at the annual meeting of the American Society of Hematology, in December 2009.
EINSTEIN-PE, which is ongoing, compares rivaroxaban to overlap therapy with enoxaparin and VKA in the treatment of almost 4,000 patients with acute symptomatic PE, for the prevention of recurrent VTE.
Rivaroxaban is a novel oral anticoagulant being evaluated for the prevention and treatment of a broad range of disorders in which blood clotting plays a major role. In clinical studies, the compound has shown no requirement for routine anticoagulation monitoring, and limited risk for food and drug interactions. The extensive program of clinical trials evaluating rivaroxaban makes rivaroxaban the most studied oral, direct Factor Xa inhibitor in the world today. More than 65,000 patients are expected to enroll in the rivaroxaban clinical development program. Rivaroxaban is being developed jointly by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., which is part of the Johnson & Johnson family of companies, and Bayer HealthCare AG.
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from J&JPRD and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 3, 2010. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither J&JPRD nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)
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1. Comparator dosing : Enoxaparin 1.0 mg/kg twice daily with oral vitamin K antagonist (VKA) treatment until the international normalized ratio (INR) was ≥ 2.0 on 2 consecutive measurements (minimum 5 days with at least 4-5 day overlap), followed by VKA for 3, 6, or 12 months (as determined by investigator).
2. Major bleeding was defined as overt bleeding associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cell or whole blood, or bleeding that occurs in a critical site or contributes to death.
3. Clinically relevant non-major bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, an unscheduled contact with a physician, cessation of study treatment, or associated with discomfort for the patient such as pain, or impairment of activities of daily life.
4. Cardiovascular-related outcomes were defined as ST segment elevation myocardial infarction (STEMI), unstable angina, TIA, ischaemic stroke, Non-ST elevation MI (NSTMI) and non-CNS systemic embolism.
5. Eriksson BI. N Engl J Med 2008; 358: 2765-2775.
6. Kakkar AK. Lancet 2008; 372: 1-9.
7. Lassen MR. N Engl J Med 2008; 358: 2777-2786.
8. Turpie A. Lancet 2009; 373: 1673-80.
9. Büller, Harry. Once-Daily Oral Rivaroxaban Versus Placebo in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism. The Einstein-Extension Study. 51st ASH Annual Meeting and Exposition, New Orleans, LA, December 8, 2009.
10. Weitz JI. Management of venous thromboembolism: present and future. Circulation. 2004 Aug 31;110(9 Suppl1):I2.