Press Releases

RIDGEFIELD, Conn., Dec. 6 /PRNewswire/ -- Boehringer Ingelheim today announced results from the RE-COVER(TM) study investigating dabigatran etexilate (150 mg BID), a direct thrombin inhibitor (DTI),(2) compared to dose-adjusted warfarin in patients with acute VTE. Results of the trial were presented at the 51st American Society of Hematology Annual Meeting and simultaneously published online in the New England Journal of Medicine.(1)

Dabigatran etexilate met the primary outcome of the trial, six month incidence of recurrent symptomatic VTE and related deaths, and was non-inferior to dose-adjusted warfarin in patients with acute VTE (2.4 percent versus 2.1 percent).(1) There were 37 percent fewer patients treated with dabigatran etexilate (71) who experienced major or clinically relevant non-major bleeds versus patients treated with warfarin (111).(1) The percentage of patients experiencing major bleeds was 1.6 in the dabigatran etexilate group and 1.9 in the warfarin group.(1) The number of patients with any bleeding was 29 percent lower in the group treated with dabigatran etexilate.(1)

Among adverse events with an incidence of at least three percent, dyspepsia was the only one that was more common between treatment arms (2.9 percent in the dabigatran etexilate group versus 0.6 percent in the warfarin group).(1) There were 115 patients in the dabigatran etexilate group (9.0 percent) and 86 patients in the warfarin group (6.8 percent) who had an adverse event that led to discontinuation of the study drug (HR, 1.33; 95 percent CI, 1.01 to 1.76; P=0.05).(1)

"The standard of care for patients with VTE is anticoagulation," said Dr. Janet Schnee, clinical program director, Boehringer Ingelheim Pharmaceuticals, Inc. "It is encouraging to see that the results of this study suggest that dabigatran etexilate has the potential to be an alternative treatment for VTE."

Venous thromboembolism is a condition which includes deep vein thrombosis (DVT) and its potentially fatal acute complication pulmonary embolism (PE). The condition results from the formation of blood clots that block the flow of blood in the veins, most frequently occurring in the legs (DVT). Clots that become dislodged from affected veins can migrate to and obstruct the blood vessels that supply the lungs (PE). Venous thromboembolism is the third most common cause of cardiovascular death after myocardial infarction and stroke.(1)

Current guidelines recommend treating acute, clinically documented VTE with a parenteral heparin preparation for at least five days followed by oral anticoagulation with a vitamin K antagonist, such as warfarin.(3)

"We are committed to improving the treatment options for patients with thromboembolic diseases," said Wa'el Hashad, vice president, Cardiovascular and Metabolics Marketing, Boehringer Ingelheim Pharmaceuticals, Inc. "The RE-COVER study results suggest dabigatran etexilate could potentially provide a convenient treatment option for patients with VTE."

In total, four trials involving 8,900 patients are exploring dabigatran etexilate in VTE: RE-COVER(TM) and RE-COVER(TM)II in acute VTE and RE-MEDY(TM) and RE-SONATE(TM) in prevention of secondary VTE.(1,4,5,6)

About RE-COVER(TM)(1)

RE-COVER(TM) is a global, phase III, randomized, double-blind, double-dummy, parallel-group study comparing the efficacy and safety of oral dabigatran etexilate (150 mg BID) to warfarin (target INR 2.0-3.0) for six months of treatment of acute symptomatic VTE, following initial treatment with a parenteral anticoagulant approved for this indication. The study involved 2,539 patients. The primary efficacy endpoint was a composite of recurrent symptomatic VTE and deaths related to VTE.

About VTE

Venous thromboembolism refers to blood clots (thrombi) which originate in the veins, and includes DVT and its potentially fatal acute complication PE. Pulmonary embolism is a leading cause of in-hospital death, accounting for approximately 10 percent of all hospital deaths.(7)

About dabigatran etexilate

Dabigatran etexilate is an investigational oral DTI,(2) being studied in the prevention and treatment of acute and chronic thromboembolic diseases.(4,5,6,8,9,10,11,12,13,14) Dabigatran etexilate is not approved by the FDA. Dabigatran etexilate is approved and marketed as Pradaxa® in 40 countries outside the U.S. for the primary prevention of venous thromboembolic events (blood clots) in patients who have undergone elective total hip or elective total knee replacement surgery.

About the dabigatran etexilate clinical trial program

RE-COVER(TM) is part of Boehringer Ingelheim's clinical trial program evaluating the efficacy and safety of dabigatran etexilate. (4,5,6,8,9,10,11,12,13,14) In addition to RE-COVER, the development program encompasses studies in:

    --  Primary prevention of VTE in patients undergoing elective total hip and
        knee replacement surgeries (10,11,14)

    --  Treatment of acute VTE (4)

    --  Secondary prevention of VTE (5,6)

    --  Prevention of atherothrombotic events in patients with acute coronary
        syndrome(9)

    --  Stroke prevention in atrial fibrillation (13)

About Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and approximately 41,300 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of US $17 billion (11.6 billion euro) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

References

(1) Schulman S, et al. "Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism." New England Journal of Medicine. 2009; 361.

(2) Di Nisio M, et al. "Direct Thrombin Inhibitors." New England Journal of Medicine. 2005; 353: 1028-40.

(3) Kearon C, et al. Antithrombotic Therapy for Venous Thromboembolic Disease. CHEST. 2008; 133: 454S-545S.

(4) ClinicalTrials.gov. "A Phase III, Randomised, Double Blind, Parallel-Group Study of the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism, Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00680186?term=dabigatran+etexilate&rank=7. Accessed on: August 25, 2009.

(5) ClinicalTrials.gov. "A Randomised, Multicenter, Double-Blind, Active Controlled Study to Investigate the Efficacy and Safety of Dabigatran Etexilate, 150 mg b.i.d Administered Orally (Capsules) for 18 Months, Compared to Warfarin Tablets p.r.n. (Target INR) for the Secondary Prevention of Venous Thromboembolism." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00329238?term=dabigatran&rank=12. Accessed on: January 28, 2009.

(6) ClinicalTrials.gov. "Twice-Daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long-Term Prevention of Recurrent Symptomatic Proximal Venous Thromboembolism in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00558259?term=dabigatran&rank=1. Accessed on: April 15, 2009.

(7) Sandler DA, et al. "Autopsy Proven Pulmonary Embolism in Hospital Patients: Are We Detecting Enough Deep Vein Thrombosis?" Journal of the Royal Society of Medicine 1989; 82: 203-205.

(8) Connolly SJ, et al. "Dabigatran versus Warfarin in Patients with Atrial Fibrillation." New England Journal of Medicine.2009; 361: 1139-51.

(9) ClinicalTrials.gov. "RandomizEd Dabigatran Etexilate Dose Finding Study in Patients With Acute Coronary Syndromes Post Index Event With Additional Risk Factors for Cardiovascular Complications Also Receiving Aspirin and Clopidogrel: Multi-Centre, Prospective, Placebo Controlled, Cohort Dose Escalation Study (RE-DEEM)." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00621855?term=dabigatran&rank=11. Accessed on: January 28, 2009.

(10) Eriksson BI, et al. "Dabigatran Etexilate Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Hip Replacement: a Randomized, Double-Blind, Non-Inferiority Trial." The Lancet. 2007; 370: 949-956.

(11) The RE-MOBILIZE Writing Committee. "Oral Thrombin Inhibitor Dabigatran Etexilate vs North American Enoxaparin Regimen for Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery." The Journal of Arthroplasty. 2009; 24: 1-9.

(12) ClinicalTrials.gov. "A Phase III Randomised, Parallel Group, Double-Blind, Active Controlled Study to Investigate the Efficacy and Safety of Orally Administered 220 mg Dabigatran Etexilate Capsules (110 mg Administered on the Day of Surgery Followed by 220 mg Once Daily) Compared to Subcutaneous 40 mg Enoxaparin Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Arthroplasty Surgery. (RE-NOVATE II)." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00657150?term=dabogatran&rank=7. Accessed on: January 28, 2009.

(13) ClinicalTrials.gov. "RELY-ABLE Long Term Multi-center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation Who Completed RE-LY Trial and a Cluster Randomised Trial to Assess the Effect of a Knowledge Translation Intervention on Patient Outcomes." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00808067?term=dabigatran&rank=10. Accessed on: July 23, 2009.

(14) Eriksson BI, et al. "Oral Dabigatran Etexilate vs. Subcutaneous Enoxaparin for the Prevention of Venous Thromboembolism After Total Knee Replacement: the RE-MODEL Randomized Trial." Journal of Thrombosis and Haemostasis. 2007; 5: 2178-2185.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

NEW ORLEANS, Dec. 6 /PRNewswire-USNewswire/ -- Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured. Sometimes, however, clots form on the inside of vessels without an obvious injury or do not dissolve naturally, a potentially life-threatening situation requiring treatment. Research presented today at the 51st Annual Meeting of the American Society of Hematology reveals that the practice of using the anticoagulants aspirin and heparin with the hope of preventing clots in placental blood vessels is ineffective for preventing unexplained, recurrent miscarriages. Two other studies look at treatments for venous thromboembolism, a common and sometimes deadly clotting disorder.

"Anticoagulants are one of the most common types of medications in use today and help prevent and treat a wide variety of health conditions," said Bradford S. Schwartz, MD, moderator of the press conference highlighting this research and Professor of Medicine and Biochemistry, and Dean of the University of Illinois College of Medicine at Urbana-Champaign. "That's why it's so critical that studies examining both newer formulations and old standbys, like aspirin, provide practitioners with the most up-to-date evidence to ensure that they are being used appropriately and that the best option is chosen for each individual patient."

This press conference will take place on Sunday, December 6, at 8:00 a.m.

Dabigatran Etexilate Versus Warfarin in the Treatment of Venous Thromboembolism

[Abstract #1]

A new study provides welcome news for patients with a common clotting disorder known as venous thromboembolism (VTE). According to the Venous Disease Coalition, 1 million Americans experience VTE every year, which occurs when an abnormal clot forms in a vein and restricts the flow of blood, causing pain and swelling. In some cases, the clot may detach from its point of origin and travel through the heart to the lungs, causing a potentially fatal condition known as a pulmonary embolism.

Currently, patients with VTE are treated with a blood thinner known as warfarin, which has many burdensome interactions with other medications and foods and requires frequent monitoring of the dosage. However, this study shows that an oral drug called dabigatran etexilate, which does not have these disadvantages, is as safe and effective as warfarin for combating VTE.

To compare the two drugs, an international team of researchers conducted a randomized, double-blind trial of 2,539 patients with acute VTE. For six months, roughly half of the patients in the trial (1,274) were given a fixed dose of 150 mg of dabigatran etexilate twice daily, while the other half (1,265 patients) were given warfarin once daily in doses adjusted to an International Normalized Ratio (INR) of 2.0 to 3.0. INR is a blood test needed to monitor the effects of warfarin therapy to ensure an adequate, yet safe, dose is taken; in this study, the test was performed, on average, every 11 days.

The improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.2 percent of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 207 patients experienced bleeding (including 20 patients with major bleeding) versus 280 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups.

"We are excited by these findings and feel that they will change the standard of care for venous thromboembolism, which affects a large number of our patients," said lead study author Sam Schulman, MD, Professor of Medicine, Thrombosis Service, McMaster Clinic and Hamilton General Hospital in Ontario, Canada. "This study found that dabigatran is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner."

Dr. Schulman will present this study during the Plenary Scientific Session on Sunday, December 6, at 2:00 p.m. in Hall F.

Aspirin and Aspirin Combined With Low-Molecular-Weight Heparin in Women with Unexplained Recurrent Miscarriage: A Randomized Controlled Multicenter Trial (ALIFE Study)

[Abstract #488]

Recurrent miscarriages are extremely traumatic and stressful for women, and, according to the American Society for Reproductive Medicine, the cause is unknown in more than 50 percent of cases.(1) Though treatments to avoid these tragedies remain elusive, some practitioners suspect that abnormal clots in the blood vessels that nourish the placenta are responsible for many recurrent miscarriages, and thus they have increasingly used aspirin and low-molecular-weight heparin to prevent further miscarriages, even though evidence to support their use is not available. Both medications are blood thinners and are used to prevent clots in the placenta that could cut off the supply of nutrients to a growing baby, or to decrease the risk of other pregnancy complications that might be causing the miscarriages.

To test the effectiveness of these controversial treatments, a team of researchers from the Netherlands conducted a multicenter, randomized clinical trial of 364 women between the ages of 18 and 42 who were attempting to conceive or were less than six weeks pregnant. The women had previously experienced at least two unexplained miscarriages by the 20th week of pregnancy. Because the researchers were focused on miscarriages with unexplained causes, women with previous venous or arterial thromboembolism (clotting disorders), endocrine disorders, or other indications for anticoagulant treatment during pregnancy were excluded from the study.

"The study clearly demonstrates that aspirin combined with heparin and aspirin alone do not prevent recurrent, unexplained miscarriages and that we should not needlessly put these women through the inconvenience and risks associated with these blood-thinning medications," said lead study author Stef P. Kaandorp, MD, research fellow in the Department of Obstetrics and Gynecology at the Academic Medical Center in Amsterdam. "These results are extremely important because they will likely change the way some women at high risk for another miscarriage have been treated."

During the study, three treatment groups were compared: aspirin and nadroparin (a low-molecular-weight heparin), aspirin alone, and placebo. Oral medication was administered once a day beginning on the day of inclusion in the study through 36 weeks of gestational age, or until miscarriage, ectopic pregnancy, or premature delivery. Patients on the oral regimens received either placebo pills or 100 mg of calcium carbasalate (a salt formulation of aspirin equivalent to 80 mg of aspirin). Women who were to receive low-molecular-weight heparin received subcutaneous injections once a day of 2,850 international units of nadroparin from six weeks of gestational age through 12 hours before delivery.

The intention-to-treat analysis of the study showed that the live birth rate did not differ significantly among the three treatment groups: 54.5 percent of those in the aspirin and nadroparin group had a live birth (67 women), compared with 50.8 percent in the aspirin group (61 women), and 57 percent of the placebo group (69 women). Side effects, most notably skin reactions, also occurred more often in women assigned to the aspirin and nadroparin group.

Dr. Kaandorp will present this study during an oral session on Monday, December 7, at 3:00 p.m. in Room 275-277.

Once-Daily Oral Rivaroxaban Versus Placebo in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism, the EINSTEIN-Extension Study [Abstract #LBA-2]

Venous thromboembolism (VTE), a condition in which a blood vessel is blocked by a clot, is a common and potentially life-threatening disorder. In the United States, there are more than 200,000 new cases of VTE that occur annually.(2) Treatment for acute VTE typically consists of an anticoagulant, such as a vitamin K inhibitor, for a period of six to 12 months. Following this, the decision to continue the treatment to prevent future clots is controversial. Long-term use of vitamin K inhibitors carries the risk of serious side effects, such as major bleeding, and requires regular laboratory monitoring to optimize the dose while reducing these risks. As an alternative, the safety and efficacy of rivaroxaban, an oral anticoagulant that does not require continued monitoring and dose adjustment, was studied for long-term therapy and found to be safe and effective.

Researchers enrolled 1,197 patients in a double-blind trial involving 280 study sites in 28 countries. Prior to enrollment, the study participants had completed six to 12 months of anticoagulant treatment for acute VTE and were randomized to receive either 20 mg of rivaroxaban once daily (602 patients) or placebo (594 patients) for an additional six to 12 months.

Treatment with rivaroxaban was found to be both safe and effective. Only eight patients (1.3 percent) on rivaroxaban showed signs of recurrent VTE events, compared with 42 patients (7.1 percent) in the placebo arm. In the rivaroxaban arm, four patients (0.7 percent) experienced major bleeding, though none of these events were fatal or at a critical site. Non-major bleeding, such as a nose bleed, skin hematoma (a swelling of blood), or blood in the urine, occurred in 32 patients (5.4 percent) taking rivaroxaban. In the placebo arm, there were no incidences of major bleeding, though seven patients (1.2 percent) experienced non-major bleeding. After the study medication was stopped, six symptomatic recurrent VTE events occurred in each group during a one-month observational period.

"The results of this study are very compelling," said lead study author Harry R. Buller, MD, Ph.D., Professor of Medicine in the Department of Vascular Medicine at the Academic Medical Center in Amsterdam. "For these patients in danger of having another VTE event, rivaroxaban lowered their risk by 82 percent without significantly increasing their risk of major bleeding. This once-daily pill provides the clinician with a simple option for patients in whom continued anticoagulant treatment is indicated."

Dr. Buller will present this study in the Late-Breaking Abstracts Session on Tuesday, December 8, at 7:30 a.m. in Hall F.

American Society of Hematology 51st Annual Meeting

The study authors and press program moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on preventing complications and improving outcomes in transplantation, advances in diagnosing and treating leukemia and myeloproliferative disorders, developments in cancer care and quality of life, and new trends and treatment options for sickle cell disease. For the complete annual meeting program and abstracts, visit www.hematology.org/2009abstracts. Up-to-date annual meeting information can also be obtained by following ASH on Twitter at ASH_hematology.

The American Society of Hematology (www.hematology.org) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology. ASH provides Blood: The Vital Connection (www.bloodthevitalconnection.org), a credible online resource addressing bleeding and clotting disorders, anemia, and cancer. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.

(1) American Society for Reproductive Medicine. Patient's Fact Sheet on Recurrent Pregnancy Loss. Available at: http://www.asrm.org/Patients/FactSheets/recurrent_preg_loss.pdf.

(2) American Heart Association. Venous Thromboembolism and Pulmonary Embolism - Statistics. Available at: http://www.americanheart.org/downloadable/heart/1200598191688FS29VTE08.pdf. Accessed November 24, 2009.

SOURCE American Society of Hematology

Late-Breaker Data Presented at Annual Meeting of the American Society of Hematology

NEW ORLEANS--(BUSINESS WIRE)-- Johnson & Johnson Pharmaceutical Research and Development, L.L.C. (J&JPRD), announced today that results from the Phase III EINSTEIN-Extension (EXT) clinical trial of the novel oral anticoagulant rivaroxaban showed a significant reduction in the risk of recurrent symptomatic venous thromboembolism (VTE), compared to placebo, in patients who have been treated for a previous deep vein thrombosis (DVT) or pulmonary embolism (PE). The rate of major bleeding was low. The findings were reviewed at today's press briefing during the 51st Annual Meeting of the American Society of Hematology (ASH), and will be fully presented as part of the late-breaker session of the general meeting at 7:30 AM CST, Tuesday, December 8th.

To be eligible for enrollment in EINSTEIN-EXT, patients had to have previously completed six to 12 months of treatment with a vitamin K antagonist (VKA) for an acute episode of VTE or have participated in the ongoing Phase III 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.

Rivaroxaban was well tolerated. Patients treated with rivaroxaban showed a highly statistically significant relative risk reduction (RRR) of 82% in the recurrence of a symptomatic VTE1 versus those treated with placebo [1.3% vs. 7.1%, (p<0.0001), respectively].

"The results from EINSTEIN-EXT highlight the potential clinical benefit of extending prophylaxis for an additional six or 12 months beyond the currently recommended treatment duration," said Harry R. Buller, M.D., Academic Medical Center in Amsterdam. "This study could help transform the way physicians treat patients who have previously suffered a DVT or PE. Currently, up to 10% of patients who are treated adequately, according to today's recommended guidelines, still experience a recurrence within 12 months of the initial event."

Rates of major bleeding,3 the primary safety endpoint, were low and not statistically significantly different between the two groups [0.7% vs. 0.0%, (p=0.11) for the rivaroxaban and placebo arms, respectively].

A secondary endpoint measuring the composite of major and clinically relevant non-major bleeding4 showed a statistically significant difference between the two groups [6.0% vs. 1.2%, (p<0.001) in the rivaroxaban and placebo arms, respectively]. No cases of serious liver injury were reported in either group. Liver safety results included: ALT >3x ULN + T Bili >2x ULN: 0.0%5 in both groups; ALT >3x ULN: 1.9% in the rivaroxaban arm and 0.5% of patients in the placebo arm. There were no differences in cardiovascular-related events between the two treatment groups.

The abstract (LBA-2) is available at: http://ash.confex.com/ash/2009/webprogram/Paper25669.html

About EINSTEIN Clinical Trials

Approximately two million cases of DVT and nearly 600,000 cases of PE are reported each year in the United States.6 EINSTEIN is a global program of three clinical trials in approximately 8,000 patients with acute, symptomatic deep vein thrombosis (EINSTEIN-DVT, enrollment complete) or pulmonary embolism (EINSTEIN-PE, enrollment ongoing). In these two programs, patients received oral rivaroxaban 15 mg twice-daily for three weeks, followed by oral rivaroxaban 20 mg once-daily, compared with initial enoxaparin treatment followed by a VKA.

The EINSTEIN-EXT study compared the safety and efficacy of rivaroxaban to placebo in the secondary prevention of recurrent symptomatic venous blood clots by prolonging preventive treatment by six or 12 months beyond a previously completed regimen of six or 12 months of therapy. The study enrolled approximately 1,200 patients from 28 countries around the world with symptomatic DVT or PE, which is collectively referred to as VTE.

Update on Complete Response for VTE Prevention Post Total Knee and Hip Replacement Surgery

Following discussions with the U.S. Food and Drug Administration, J&JPRD is continuing to work with its partner, Bayer HealthCare, to provide additional information from the RECORD study sites, and data from ongoing studies, to adequately address issues raised in the Complete Response letter received in May 2009. Based on those discussions, J&JPRD has decided it will not submit its complete response to the FDA seeking approval of rivaroxaban for the prevention of DVT and PE in patients undergoing hip or knee replacement surgery by the end of 2009.

Postponing the complete response until these requirements are fully addressed provides the greatest opportunity for successfully bringing rivaroxaban through the regulatory process. An updated filing strategy will be communicated following completion of these ongoing discussions.

About Rivaroxaban

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 a rapid onset of action with a predictable dose response and high bioavailability, 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 and 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 December 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. Neither Johnson & Johnson nor J&JPRD, undertake to update any forward-looking statements as a result of new information or future events or developments.)

Notes/References

1. Secondary prevention of recurrent symptomatic VTE is defined as a composite of recurrent DVT, non-fatal PE, fatal PE, and unexplained death for which PE cannot be ruled out.

2. Semin Nucl Med. 2001 Apr;31 (2):90-101.

3. 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.

4. Clinically relevant but non-major bleeding was defined as bleeding not meeting the criteria for major bleeding but is associated with medical intervention.

5. ALT >3x ULN + T Bili >2x ULN = Levels of alanine aminotransferase (ALT) greater than three times the upper limit of normal (ULN) plus Total Bilirubin greater than two times the ULN

6. Gerotziafas GT. CurrOpin PulmMed.2004; 10:356-365.

    Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

RIO DE JANEIRO, Dec. 6 /PRNewswire/ -- The traditional inauguration of the largest floating Christmas tree in the world according to the Guinness Book of Records - 85-meters-tall (equivalent to a 28-story building) - sponsored by Bradesco Seguros e Previdencia, gathered together thousands of people on Saturday in Rio de Janeiro, Brazil. The lighting of the tree is considered the city's third largest event after Carnival and New Year's Eve. An international reference for Christmas, which, according to the mayor's office, attracts nearly 80,000 visitors per day, the tree will remain on display until Epiphany Day, January 6, when it will be lit up for the last time.

(Photo: http://www.newscom.com/cgi-bin/prnh/20091206/SPSU001 )

The theme of this 14th consecutive edition of the Bradesco Seguros e Previdencia's Christmas Tree is "The Joyous Uniting of Our Best Wishes." The monument, which has been a focal point of Christmas celebrations in Brazil and abroad since 1996, was decorated for the first time with traditional Christmas garlands representing the full range of everybody's year-end holiday wishes.

The scenic tree once again was created by Brazilian designer Abel Gomes, who spared no inventiveness in order to provide its spectators a magnificent show of lights and colors: 11 sequential patterns, illuminated by 2.9 million miniature bulbs, 52 kilometers of illuminated strands and 1,600 strobes (small bulbs with a flashing, stroboscopic effect), producing a twinkling star effect.

The light and color display presented by the largest floating Christmas tree in the world is powered by biodiesel generators that help reduce carbon dioxide (CO2) emissions into the atmosphere. To optimize the use of fuel, a computerized telemetry system is used that activates the generators based on the requirements of the programmed lighting.

The CO2 emissions into the atmosphere caused by the set-up, exhibition and dismantling of the 2009 edition of the tree will be neutralized by the planting of trees.

    For more information:

    Vera Soares - Superintendent of Communication
    Phone: (5521) 2503-1808
    Cell phone: (5521) 9971-2379
    vera.soares@bradescoseguros.com.br

    Diferencial
    Cristina Guimaraes - Press Advisor
    Phone: 5511 3024 5887 / Cell phone: 5511 9307 6562
    cristinaguimaraes@diferencial-mkt.com.br

SOURCE Bradesco Seguros e Previdencia

BEIJING and SANTA CLARA, Calif., Dec. 6 /PRNewswire-FirstCall/ -- AsiaInfo Holdings, Inc. (Nasdaq: ASIA) ("AsiaInfo" or "the Company") and Linkage Technologies International Holdings Limited ("Linkage"), leading providers of software solutions and IT services for the telecommunications industry in China, today jointly announced that they have signed a definitive agreement to merge, forming AsiaInfo-Linkage, Inc. ("AsiaInfo-Linkage"). The transaction will leverage both AsiaInfo's and Linkage's leading market positions and complementary customer bases to provide a robust, full-service offering to telecom operators.

Under the terms of the agreement, Linkage shareholders will receive US$60 million in cash and approximately 26.8 million AsiaInfo shares upon closing of the transaction. Based on the closing price of AsiaInfo's stock on December 4, 2009, the combined company would have a market value of over US$1.8 billion. Post-transaction, Linkage's legacy shareholders will own approximately 35.8% of AsiaInfo-Linkage with AsiaInfo's legacy shareholders owning approximately 64.2%. The transaction is expected to be accretive to non-GAAP earnings per share in 2010.

Upon completion of the transaction, AsiaInfo-Linkage will have over 8,000 employees, of which approximately 7,000 are engineers dedicated to project delivery and research and development. The combined company will also have 34 patents and an additional 27 patents pending approval in China and the United States.

"We are creating the pre-eminent software solutions provider in China's telecommunications industry," said Mr. Steve Zhang, AsiaInfo's president and chief executive officer. "The combined company's expanded service offering, extensive base of highly skilled engineers, world class R&D capabilities and complementary customer bases will enable us to better service and anticipate our customers' needs. Going forward, we will leverage our products and services which range from system implementation and maintenance services to high-value consulting in order to capitalize on China's fast-growing telecom software industry. In addition to growing our business domestically, the merged company will explore new revenue drivers by looking abroad."

"This is a very exciting development and milestone for our company and an important move that will benefit China's telecom software industry," commented Mr. Libin Sun, Linkage's chairman and chief executive officer. "For more than 10 years, AsiaInfo and Linkage have developed innovative products, built strong relationships with all three telecom operators in China and have delivered strong financial results. In fact, from 2006 to 2008, Linkage's total revenues and net income grew at compounded annual growth rates of approximately 37.4% and 36.5%, respectively. With common business strategies and a plan to fully integrate our management teams and internal systems, I am confident that we will be able to quickly identify business opportunities and realize value for our shareholders."

Upon closing, Mr. Steve Zhang, AsiaInfo's president and chief executive officer, will become president and chief executive officer of AsiaInfo-Linkage. AsiaInfo-Linkage's board of directors will comprise of nine members, consisting of six members from AsiaInfo's board and three members appointed by Linkage's board. Mr. Libin Sun, Linkage's chairman and chief executive officer, will serve as AsiaInfo-Linkage's executive co-chairman and Mr. James Ding, AsiaInfo's chairman, will serve as AsiaInfo-Linkage's co-chairman.

The merger has been approved by both companies' boards of directors and is subject to customary closing conditions including the receipt of any regulatory approvals and the approval of AsiaInfo's shareholders. The transaction is expected to close by the end of the first quarter or early in the second quarter of 2010.

BofA Merrill Lynch and The Hina Group acted as financial advisors and DLA Piper and Han Kun Law Office acted as legal advisors to AsiaInfo in connection with the transaction. Barclays Capital served as financial advisor and Latham & Watkins and Global Law Office served as legal advisers to Linkage.

Conference Call Details

AsiaInfo management will hold a conference call at 5:00 a.m. Pacific Time / 8:00 a.m. Eastern Time on December 7, 2009 (9:00 p.m. Beijing/Hong Kong Time on December 7, 2009). Management will discuss the merger in more detail and answer questions from analysts and investors.

The dial-in numbers for the conference call are as follows:

U.S. Toll Free: +1-888-830-9551

China Toll Free Number (China Netcom): 10800-852-1039

China Toll Free Number (China Telecom): 10800-152-1039

Hong Kong and International: +852-3002-1675

The passcode for the conference call is 67339161.

A replay of the call will be available until 8:00 a.m. Eastern Time on December 22, 2009 by dialing one of the following numbers:

U.S. Toll Free: +1-617-213-4164

Hong Kong and International: +852-3011-4542

The passcode for the replay of the conference call is 67339161.

Additionally, a PowerPoint will be posted under the investor relations section of the company's website which can be downloaded and used to follow along on the call.

About AsiaInfo Holdings, Inc.

AsiaInfo Holdings, Inc. (Nasdaq: ASIA) is a leading provider of high-quality software and customer solutions to many of China's largest enterprises. In addition to providing software and customer solutions to China's telecom carriers, the Company also offers a wide range of security products and services to small, medium and large sized Chinese enterprises across multiple vertical industries.

Organized as a Delaware corporation, AsiaInfo began operations in the United States in 1993. The Company moved its major operations to China in 1995 and played a significant role in the construction of the national Internet backbones and provincial access networks for all of China's major national telecom carriers, including China Telecom, China Mobile and China Unicom. Since 1998, AsiaInfo has continued to diversify its product offerings and is now a major provider of enterprise software solutions in China.

For more information about AsiaInfo, please visit http://www.asiainfo.com.

Linkage Technologies International Holdings Limited

Linkage Technologies International, based in Nanjing, China, was founded in 1997 and is a leading provider of software solutions and IT services for the telecom industry in China. The company develops and implements Business Support Systems ("BSS"), Operation Support Systems ("OSS") and Business Intelligence Systems ("BI") for all three operators in China.

For more information about Linkage, please visit http://www.lianchuang.com.

Cautionary Note Regarding Forward-Looking Statements

The information contained in this press release is as of December 6, 2009. We assume no obligation to update any forward-looking statements contained in this press release as a result of new information or future events or developments. This press release contains forward-looking information about future performance, revenue and cost synergies, cross-selling opportunities and other anticipated outcomes of the business combination of AsiaInfo Holdings and Linkage Technologies. Among the factors that could cause actual results to differ materially are the following: the anticipated timing of filings and approvals relating to the proposed business combination; the satisfaction of other closing conditions; the expected timing of the completion of the acquisition; the ability to successfully integrate the products, services and employees of AsiaInfo and Linkage; the ability to successfully develop and market new products and services, and the uncertainty of whether our products and services will achieve market acceptance or result in revenue growth; and the continued performance or market growth of the combined company's products and services. A further list and description of these risks, uncertainties, and other matters can be found in AsiaInfo's Annual Report on Form 10-K for the fiscal year ended December 31, 2008, and in our periodic reports on Forms 10-Q and 8-K filed with the United States Securities and Exchange Commission and available at www.sec.gov.

ASIAINFO HOLDINGS INTENDS TO FILE A PROXY STATEMENT WITH THE SECURITIES AND EXCHANGE COMMISSION (THE "SEC") RELATING TO ASIAINFO'S SOLICITATION OF PROXIES FROM THE SHAREHOLDERS OF ASIAINFO FOR USE AT A SPECIAL MEETING OF SHAREHOLDERS. ALL ASIAINFO SHAREHOLDERS ARE URGED TO READ THE PROXY STATEMENT FILED WITH THE SEC CAREFULLY IN ITS ENTIRETY WHEN IT BECOMES AVAILABLE BECAUSE IT WILL CONTAIN IMPORTANT INFORMATION. SHAREHOLDERS WILL BE ABLE TO OBTAIN FREE COPIES OF THE PROXY STATEMENT FILED WITH THE SEC BY ASIAINFO AT WWW.ASIAINFO.COM, AND THROUGH THE WEB SITE MAINTAINED BY THE SEC AT WWW.SEC.GOV.

For investor and media inquiries, please contact:

In China:

Sheryl Zhang
AsiaInfo Holdings, Inc.
Tel: +86-10-8216-6039
Email: ir@asiainfo.com

Justin Knapp
Ogilvy Financial, Beijing
Tel: +86-10-8520-6556
Email: asia@ogilvy.com

In the United States:

Ms. Jessica Barist Cohen
Ogilvy Financial, New York
Tel: +1-646-460-9989
Email: asia@ogilvy.com

SOURCE AsiaInfo Holdings, Inc.