Findings to be presented at Annual Scientific Session of the American College of Cardiology (ACC) about an additional potential reversal strategy for and real-world safety performance of XARELTO

RARITAN, N.J., March 2, 2015 -- Full results from a Phase 3 study examining Portola Pharmaceutical's developmental compound andexanet alfa found it rapidly and significantly reversed the blood thinning (anticoagulant) effects of XARELTO (rivaroxaban). These results, from the first part of the ANNEXA-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXa Inhibitors – Rivaroxaban) study, will be presented at the 64th Annual Scientific Session of the American College of Cardiology (ACC) on March 16, 2015. Additional findings to be presented at the meeting include new 24-month results from an ongoing, five-year, observational study of people with non-valvular atrial fibrillation taking XARELTO, which showed the rates and patterns of major bleeding in routine clinical practice were generally consistent with those observed in Phase 3 clinical trials used to approve the medicine for this indication.

Janssen and its development partner, Bayer HealthCare, previously entered into a second clinical collaboration agreement with Portola to initiate the Phase 3 study to evaluate Portola's investigational Factor Xa inhibitor agent, andexanet alfa, in reversing the blood thinning effect of XARELTO, should the need arise. This clinical collaboration will be in effect through completion of the Phase 3 study with XARELTO and any potential U.S. and EU regulatory approval of andexanet alfa. The second part of the Phase 3 ANNEXA-R study, evaluating a continuous infusion of andexanet alfa, is ongoing.

Specifically, this first part of the ANNEXA-R study found andexanet alfa, when administered as an intravenous bolus dose, significantly reversed the anti-clotting effect of XARELTO. In the randomized, double-blind, placebo-controlled study, a total of 41 healthy adults age 50 to 75 were given XARELTO 20 mg once daily for four days to steady state. On day four, participants were randomized in a 2:1 ratio to receive either an 800 mg intravenous dose of andexanet alfa or placebo. Efficacy was evaluated using biomarker endpoints, with anti-Factor Xa levels as the primary endpoint. Secondary endpoints included plasma levels of unbound XARELTO and thrombin generation levels. All primary and secondary endpoints were met with statistical significance (p<0.0001). Andexanet alfa was well tolerated with no serious or severe adverse events reported.

These findings add to existing published research examining reversal measures for blood thinners:

Prior research on potential reversal options for XARELTO include a Phase 2 study published in the Journal of Thrombosis and Haemostasis, which showed prothrombin complex concentrate, or PCC, partially reversed the blood thinning effect of XARELTO in healthy people. In the study, 35 adults were treated with 20 mg of XARELTO twice daily for four days. On the fifth day, an intravenous dose of PCC (either three-factor or four-factor) or a single control dose of saline was given. The PCCs (both three-factor and four-factor) were found to partially reverse the anti-clotting effect of XARELTO.

Vitamin K, a common reversal option for patients taking warfarin, can take up to 24 hours to reverse the anticoagulant effect of warfarin. Notably, stopping treatment with XARELTO may allow for patients to return to near-normal levels of coagulation within 24 hours.

"Patients taking blood thinners are doing so to treat or help prevent life-threatening blood clots from forming in their body. If the need arises to stop this effect, andexanet alfa may add to current reversal strategies for XARELTO," said Paul Burton, M.D., Ph.D., Vice President, Medical Affairs, Janssen. "Stopping treatment with XARELTO may allow for patients to return to near-normal levels of coagulation within 24 hours. In addition, the use of prothrombin complex concentrate, or PCC, has been observed to partially reverse the anticoagulant or blood thinning activity of XARELTO in healthy people."

Real-World Safety Data Also to be Presented at ACC

At ACC on March 15, 2015, Janssen will also present new, confirmatory, real-world safety data of people with non-valvular atrial fibrillation (NVAF) taking XARELTO. Specifically, 24-month results from an ongoing, five-year, observational study of people with NVAF found the rates and patterns of major bleeding in routine clinical practice were generally consistent with those observed in Phase 3 clinical trials used to approve XARELTO for this indication.

"We are pleased with these findings that reaffirm the safety profile of XARELTO," said Dr. Burton. "With studies completed in over 85,000 patients and ongoing post-marketing studies that will include more than 74,000 patients, we continue to provide real-world data to equip doctors with the information that they need to optimize care for people taking XARELTO."

In this study, researchers reviewed health records of people with NVAF using once-daily XARELTO. Of the 39,052 people taking XARELTO, 970 experienced a major bleeding event, which translated into an incidence rate of 2.89 per 100 person-years. Incidence rate was calculated using a person-time approach: the total number of people experiencing major bleeding divided by the number of years of all people receiving XARELTO (expressed in 100-year increments).

About XARELTO (rivaroxaban)

XARELTO works by blocking the blood clotting Factor Xa. XARELTO does not require routine blood monitoring. XARELTO has a broad indication profile and is approved for six indications that include:

To reduce the risk of strokes and blood clots in patients with atrial fibrillation not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO and warfarin compare in reducing the risk of stroke.

To treat patients with deep vein thrombosis (DVT).

To treat patients with pulmonary embolism (PE).

To reduce the risk of recurrence of DVT or PE following an initial six-month treatment for acute venous thromboembolism.

To reduce the risk of blood clots in the legs and lungs of patients who have just had knee replacement surgery.

To reduce the risk of blood clots in the legs and lungs of patients who have just had hip replacement surgery.

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Pharmaceuticals, Inc. is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.