Biotech Values

[DewDiligence]

Bayer, JNJ Report Phase-2 Xarelto Data in ACS

[The companies made the decision in August to advance Xarelto to phase-3 for ACS (#msg-31857009), but the phase-2 data were not reported until now. The primary endpoint—a composite of all-cause death, MACE, and TVR—missed statsig with p=0.10; however, the secondary endpoint of all-cause death and MACE (without TVR) was statsig with p=0.03. Only the lower two doses—2.5mg and 5mg BID—will be tested in phase-3.

Xarelto (rivaroxaban) is an oral FXa inhibitor that is already approved in the EU for VTE prevention (#msg-30972846). If eventually approved in all indications where it is being tested, Xarelto figures to be the largest-selling drug Bayer has ever had (including aspirin). JNJ is handling the commercialization in the US (#msg-31073048).]

http://biz.yahoo.com/bw/081110/20081110005560.html

›Results Presented as Late-Breaker at American Heart Association Meeting

Phase III Study Expected to Initiate in December 2008

Monday November 10, 8:59 am ET

NEW ORLEANS--(BUSINESS WIRE)--Findings from the Phase II ATLAS ACS TIMI 46 study of rivaroxaban, a novel, investigational, oral anticoagulant, were presented today as a late-breaking clinical trial at the American Heart Association’s Scientific Sessions 2008 in New Orleans by C. Michael Gibson, M.D., director of the TIMI Data Coordinating Center, Harvard Medical School. Results from this Phase II study support advancing rivaroxaban into a pivotal Phase III trial for the secondary prevention of acute coronary syndrome (ACS).

As a Phase II dose-finding study, the ATLAS ACS TIMI 46 trial was designed to explore the safety and efficacy of rivaroxaban at escalating total daily doses, ranging from 5 mg up to 20 mg. Rivaroxaban was administered at once-daily and twice-daily intervals, assessing eight different dosing regimens in total. Nearly 3,500 patients were enrolled, and all patients received standard antiplatelet therapy of low-dose aspirin and, at the physician’s discretion, a thienopyridine, such as clopidogrel. Patients were then randomized to additionally receive either rivaroxaban or a placebo for six months.

“This was a robust study that achieved its main objective of establishing the preferred dosing scenario for further evaluating rivaroxaban in a large Phase III clinical trial of ACS patients,” said Dr. Gibson. “The additional benefit of rivaroxaban over placebo in this study, given on a background of standard antiplatelet therapy, highlights the unmet medical need of this patient population.”

Safety was evaluated by measuring clinically significant bleeding, defined as a composite of TIMI major bleeding, TIMI minor bleeding and any reported bleeding event requiring medical attention. As expected, rivaroxaban-treated patients exhibited higher rates of bleeding versus placebo when administered on a background of antiplatelet therapy, and there was a significant dose trend (p<0.001). However, no study arm was halted due to increased bleeding. Rates of clinically significant bleeding were:

Placebo: 3.3%, rivaroxaban 5 mg: 6.1%, 10 mg: 10.9%, 15 mg: 12.7%, 20 mg: 15.3%. Overall, 82% of the clinically significant bleeding events were not defined as TIMI major or TIMI minor. No evidence of drug-induced liver injury was seen in the study.

The primary efficacy endpoint was death, myocardial infarction (MI), stroke or severe recurrent ischemia requiring revascularization. Rivaroxaban was associated with an observed 21% Relative Risk Reduction (RRR) for the primary efficacy endpoint (p=0.1) and a 31% RRR against the secondary endpoint of death, MI or stroke (p=0.028), demonstrating a consistent trend for efficacy across doses. The study was not powered to demonstrate significance in the composite efficacy endpoint.

Though not statistically significant due to the small sample size, the two doses selected for further evaluation in the pivotal Phase III program - 2.5 mg and 5 mg dosed twice daily - showed an observed 46% RRR in the composite efficacy endpoint of death, MI or stroke when dosed in addition to aspirin, and an observed 45% RRR when dosed in combination with aspirin and a thienopyridine. Rates of TIMI major bleeding were 1.2% for each stratum. The complete ATLAS ACS TIMI 46 presentation can be accessed at http://www.timi.org.

ATLAS ACS TIMI 51

The global Phase III study, ATLAS ACS TIMI 51, is expected to begin in December 2008 with a potential enrollment of up to 16,000 patients. As in the Phase II study, all patients will receive standard care antiplatelet therapy and will then be randomly assigned to take either rivaroxaban at doses of 2.5 mg or 5 mg, or placebo, twice daily for at least six months. The primary efficacy endpoint will be a composite of cardiovascular death, MI or stroke. The primary safety endpoint will be TIMI major bleeding events not associated with coronary artery bypass graft (CABG) surgery. A study overview will be accessible at www.clinicaltrials.gov.

“ACS is a chronic, life threatening condition requiring daily therapy. While well-established therapies exist, there is a need for additional treatment options that could help improve patient outcomes. We look forward to initiating this pivotal study,” said study chairman Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and chairman of the TIMI Study Group.

About ACS

ACS is a very common and life-threatening result of coronary heart disease. It occurs when a coronary artery is blocked by a blood clot, reducing blood supply to the heart. ACS events include MI, commonly known as heart attack, and unstable angina (a very serious condition that indicates a heart attack could soon occur). Despite improvements in standard care, the AHA reports 1.4 million unique hospitalizations occurred in the U.S. in 2005 due to ACS. Nearly 40% of patients who experience one of these attacks will die in the future as a result, and up to 30% of patients who leave the hospital after an ACS event are re-admitted within the first six months.

Rivaroxaban is being developed jointly by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. and Bayer HealthCare AG.

About Rivaroxaban

The extensive clinical trial program supporting rivaroxaban makes it the most studied oral, direct Factor Xa inhibitor in the world today. More than 60,000 patients are expected to be enrolled into the rivaroxaban clinical development program, which will evaluate the product in the prevention and treatment of a broad range of blood-clotting disorders. If approved by the FDA, Ortho-McNeil, a Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. will commercialize rivaroxaban in the U.S.‹