AASLD 2011 news - 肝病学会2011新闻

StephenW

http://www.marketwatch.com/story/promedior-announces-presentation-of-preclinical-data-at-aasld-demonstrating-that-pentraxin-2-suppresses-liver-fibrosis-2011-11-02
Promedior Announces Presentation of Preclinical Data at AASLD Demonstrating that Pentraxin-2 Suppresses Liver Fibrosis                                Promedior's First-in-Class Pentraxin-2 Therapeutic, PRM-151, Represents a Promising New Mechanism for Treating a Wide Range of Fibrotic Diseases                                                                                                  
                                             
                           

   

                                                       

                           

MALVERN, Pa., Nov 02, 2011 (BUSINESS WIRE) --Promedior,       Inc., a clinical stage biotechnology company developing novel therapies       to treat fibrotic, inflammatory and neovascular diseases, today       announced that data from preclinical studies of Serum Amyloid P       (Pentraxin-2) will be presented at the Annual Meeting of the American       Association for the Study of Liver Diseases (AASLD 2011), being held       November 4-8, 2011, in San Francisco, CA. The data to be presented       highlight the efficacy and utility of Pentraxin-2 in suppressing       fibrosis and providing a clear hepatoprotective effect in independent       models of liver fibrosis. In liver fibrosis, Pentraxin-2 inhibits the       activation of monocytes, fibrocytes and hepatic stellate cells.       Promedior's lead product, PRM-151, is a recombinant form of the       naturally circulating human protein Pentraxin-2, which has been shown to       regulate the cell populations that control fibrosis, inflammation and       pathologic neovascularization.

Promedior宣布肝病学会临床前数据表明Pentraxin- 2抑制肝纤维化的呈报
Promedior的第一级Pentraxin- 2治疗，PRM -151，表示一个有前途的新机制，治疗范围广泛的纤维化疾病

宾夕法尼亚，MALVERN，2011年11月02，（美国商业资讯） - Promedior公司，开发新的疗法来治疗肝纤维化，炎症和新生血管性疾病的临床阶段的生物技术公司，今天宣布，血清淀粉样P的临床前研究的数据（Pentraxin -2）将发表在美国协会肝病（AASLD2011年）被关押在加利福尼亚州旧金山，11月4-8日2011年，研究年度会议。对提交的数据突出Pentraxin- 2的疗效和抑制纤维化的效用，在肝纤维化的独立模型提供一个明确的保肝作用。 Pentraxin-2在肝纤维化，抑制单核细胞，成纤维细胞和肝星状细胞的活化。 Promedior的主导产品，PRM- 151，是一个自然循环的人类蛋白质Pentraxin- 2，这已被证明，以调节控制纤维化，炎症和病理性新生血管形成的细胞群的重组形式。

StephenW

http://www.prnewswire.com/news-releases/jennerex-to-present-final-survival-data-from-randomized-phase-2-clinical-trial-of-jx-594-in-advanced-liver-cancer-at-american-association-for-the-study-of-liver-diseases-annual-meeting-133061643.html
Jennerex to Present Final Survival Data From Randomized Phase 2 Clinical Trial of JX-594 in Advanced Liver Cancer at American Association for the Study of Liver Diseases Annual Meeting


-- Randomized Phase 2 Clinical Data to be Presented in Late-Breaking Oral Session --

SAN FRANCISCO, Nov. 2, 2011 /PRNewswire/ -- Jennerex, Inc., a private clinical-stage biotherapeutics company focused on the development and commercialization of first-in-class targeted oncolytic products for cancer, today announced that final data from its Phase 2 randomized clinical trial in advanced liver cancer patients will be presented on Monday, November 7, 2011 at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) taking place November 4-8, 2011 in San Francisco, California.  These data, evaluating multi-dose administration of JX-594 in U.S., Korean and Canadian patients with advanced liver cancer, were selected for an oral presentation in the late-breaking oral session of the conference.

The presentation details are as follows:

Abstract Title: "A Randomized, Controlled Phase 2 Clinical Trial of JX-594, a Targeted Multi-Mechanistic Oncolytic Poxvirus, in Patients with Advanced Hepatocellular Carcinoma: Final Data." (Abstract #LB1)
Presenter: Tony Reid, M.D., Ph.D., professor of medicine, hematology/oncology, director of clinical investigation, and the tumor growth, invasion and metastasis program, Moores UCSD Cancer Center at the University of California, San Diego
Session: Late-Breaking Oral Session, November 7, 2011, 2:45 p.m. PT

JX-594: A Multi-Mechanistic Approach To Targeting Cancer

JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: 1) the lysis of cancer cells through viral replication, 2) the shutdown of the blood supply to tumors through vascular targeting and destruction, and 3) the stimulation of the body's immune response against cancer cells, i.e., active immunotherapy. Phase 1 and Phase 2 clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients (over 120 treated to date).

JX-594 is the most advanced product candidate from Jennerex's proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform.  SOLVE takes advantage of the natural attributes of poxviruses as well as their ability to be genetically engineered to produce safe, therapeutic viruses that can infect solid tumors both systemically and locally.  The vaccinia poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells. JX-594 was engineered to enhance this natural safety and cancer-selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack.

Jennerex出示2期随机JX - 594在美国商会中晚期肝癌的临床试验中肝病研究年度会议的最后生存资料


- 随机2期的最新口腔会议提交的临床数据 -

旧金山，2011年11月2，/新华美通/ - Jennerex公司，私人临床阶段生物疗法公司主要集中在第一级针对癌症溶瘤产品的开发和商品化，今天宣布，从它的最终数据第2阶段随机晚期肝癌患者的临床试验将在肝病研究协会第62届年会（AASLD）发生年11月4-8，2011年在旧金山，2011年11月7日（星期一），加利福尼亚州。这些数据，评估多剂量管理JX - 594在美国，韩国和加拿大的晚期肝癌患者，被选定为后期打破会议的口头会议的口头介绍。

演示文稿的详细信息如下：

摘要标题：“一个随机的，受控的第2期临床试验的JX - 594，有针对性的多机理的溶瘤痘病毒晚期肝癌患者，最终的数据” （摘要＃LB1）
主讲人：托尼里德，医学博士，哲学博士，医学教授，血液/肿瘤，临床研究主任，肿瘤的生长，侵袭和转移的方案，摩斯伦在加州大学圣迭戈分校的加州大学圣迭戈分校癌症中心
会议：最新发布的口腔会议，2011年11月7日，下午2:45 PT

JX - 594：一个多机理的针对癌症的方法

JX - 594是一种专有的工程，其目的是选择目标和摧毁癌细胞的溶瘤病毒。 JX - 594可通过三个多样化的机制行动攻击癌症：1）通过病毒复制裂解肿瘤细胞2）通过血管靶向和破坏肿瘤供血关闭，和3）对人体的刺激对癌细胞的免疫反应，即主动免疫。阶段1和阶段2在多种类型的癌症的最新临床试验表明，JX - 594的交付或者直接到肿瘤或全身，导致肿瘤缩小和/或坏死，由患者（120余种治疗的最新）耐受性良好。

JX - 594是从Jennerex的专有求解™（选择性溶瘤牛痘工程）平台上最先进的候选产品。求解需要痘病毒的自然属性，以及他们的能力，以基因工程生产安全，治疗病毒能够感染固体肿瘤系统和当地的优势。痘苗病毒痘病毒JX - 594株骨干已在亿万人民的安全使用，作为一个世界性的疫苗接种计划的一部分。这株自然目标由于在肿瘤细胞中常见的遗传性缺陷的癌细胞。 JX - 594的设计，以提高删除其胸苷激酶（TK）基因，从而使细胞的TK依赖自然的安全性和选择性癌，癌细胞持续高水平表达。为了提高产品的功效，JX - 594的设计也表达的免疫原性的GM - CSF的蛋白。 GM - CSF的补充候选产品的肿瘤细胞裂解，导致级联导致肿瘤坏死，肿瘤血管关闭和持久的抗肿瘤免疫攻击的事件。

StephenW

台灣肝病研究權威、中央研究院生命科學組院士，也被網友暱稱「台灣肝帝」的台灣大學醫學院教授陳定信，因為傑出的貢獻，成為美國肝病學會（ＡＡＳＬＤ）公布二○一一年「傑出臨床教育家∕導師獎」得主。陳定信以畢生心血培育無數肝病臨床醫生的傑出貢獻獲得殊榮，是台灣之光的又一例。陳定信將於十一月六日出席在美國舊金山舉辦的ＡＡＳＬＤ年度大會接受頒獎。
ＡＡＳＬＤ成立於一九五○年，每年大會吸引各國超過七千五百名肝臟內外科醫生、病理及基礎研究或醫療護理人員與會，是全球肝病研究重要領導機構。
ＡＡＳＬＤ推崇陳定信從一九七五在台大醫學院任教開始，就鼓勵新進醫生進行臨床醫療與實驗室研究，為台灣栽培出超過九十位胃腸病與肝病臨床醫師，目前在各大教學醫院擔任要職，也有不少成為優秀的醫師科學家。此外，陳定信在廿七年前全力協助推動台灣新生兒接種Ｂ型肝炎疫苗，對公共健康政策影響深遠。
陳定信目前是台大特聘教授，專長肝臟學。長期投入Ｂ肝致病過程、肝炎併發症、肝癌早期診斷與治療。他對慢性Ｃ型肝炎研發的新合併療法，廣為各國使用。

StephenW

                                                                         

                        press release               

                               

                                        Nov. 5, 2011, 9:00 a.m. EDT                               

                                Gilead Announces Positive Five-Year Data Showing Effect of Viread(R) on Liver Fibrosis and Cirrhosis Caused by Chronic Hepatitis B                                -- New Long-Term Data Show No Development of Resistance --新的长期的数据显示没有耐药性的发展 -

                       
               
       
       
       
                                 
                                             
                           

   

                                                       

                           

SAN FRANCISCO, Nov 05, 2011 (BUSINESS WIRE) --Gilead Sciences, Inc.                                                                 GILD                        -0.05%                                 today announced new five-year data       from the open-label phase of two pivotal Phase 3 clinical trials       (Studies 102 and 103) evaluating the efficacy of Viread(R)       (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B       virus (HBV) infection among primarily treatment-naive patients. Results       show that Viread maintains long-term viral suppression of HBV and is       associated with a reduction in liver fibrosis and a reversal of       cirrhosis. Among patients in both studies, the majority (88 percent)       experienced an improvement in overall liver histology. Together, these       two studies represent one of the largest datasets evaluating the impact       of an oral antiviral therapy on histologic changes and showing a       reduction in liver fibrosis. These findings are being presented Monday,       November 7 at the 62nd annual meeting of the American Association for       the Study of Liver Diseases (The Liver Meeting 2011) in San Francisco.

旧金山，2011年11月05，（商业资讯） - Gilead Sciences公司，公司GILD-0.05％今天宣布，从两个关键的第三期临床试验阶段开放标签（研究102和103）的新的五年的数据评估Viread（R）（富马酸替诺福韦disoproxil）的功效，用于治疗慢性乙型肝炎病毒（HBV）感染主要治疗过的患者中。结果表明，Viread保持长期抑制乙肝病毒，并在降低肝纤维化和肝硬化的逆转。在这两项研究的患者中，多数（88％）经历了一个整体的肝脏组织学的改善。总之，这两个研究代表评价口服抗病毒药物治疗的组织学变化的影响，并呈现出减少肝纤维化的最大的数据集之一。正在提交这些调查结果，11月7日（星期一）在第62届美国肝病（肝会议2011年）在旧金山研究协会的年度会议。

                           

"We have long theorized that long-term antiviral therapy can not only       help chronic hepatitis B patients achieve and maintain virologic       suppression, but also help to improve clinical outcomes, including a       reduction in the risk of fibrosis or cirrhosis," said Patrick Marcellin,       MD, of Hopital Beaujon in Clichy, France, INSERM CRB3 and University of       Paris Denis Diderot, and the principal investigator of Study 102. "These       results represent an important advance in HBV therapy because they       elucidate Viread's potential to reduce or reverse signs of liver damage       in patients with chronic hepatitis B."                                                       

                           

Studies 102 and 103 were designed to compare Viread to Hepsera(R)       (adefovir dipivoxil) in a blinded manner over 48 weeks, among both       HBeAg-negative (Study 102) and HBeAg-positive (Study 103) patients with       compensated liver disease. Patients originally randomized to Hepsera in       both studies were switched to open-label Viread at 48 weeks and patients       randomized to Viread continued on open-label Viread.                                                       

                           

The data show that the majority of patients who received Viread       continuously for 240 weeks experienced sustained suppression of HBV DNA       (viral load) levels in the blood below 400 copies/mL (83 percent and 64       percent for Studies 102 and 103, respectively). Patients who were       randomized to Hepsera and rolled over to Viread at week 48 and received       Viread for a subsequent 192 weeks also maintained viral suppression (84       percent and 66 percent for Studies 102 and 103, respectively).                                                       

                           

Notably, among the 331 patients who had paired biopsies at both baseline       and week 240, 292 (88 percent) experienced an improvement in overall       liver histology, as measured by an improvement of at least two points in       Knodell necroinflammatory score without worsening in Knodell fibrosis       score. Of the 94 patients who had cirrhosis (Ishak fibrosis score greater-than or equal to  5)       at the start of therapy, 69 (73 percent) experienced regression of       cirrhosis and 68 (72 percent) had at least a two-point reduction in       Ishak fibrosis score.                                                       

                           

Among HBeAg-positive patients receiving Viread through 240 weeks (Study       103), the cumulative probability (estimated by Two-State Markov model)       of "s" antigen loss and seroconversion was 9 percent and 7 percent,       respectively. Additionally, no resistance to Viread emerged over 240       weeks of treatment.                                                       

                           

"Viral resistance is a significant challenge for physicians treating       patients with chronic hepatitis B," said Jenny Heathcote, MD, of the       University of Toronto, Canada, and the principal investigator for Study       103. "These five-year results are important in that they demonstrate       Viread's high genetic barrier to resistance, which is essential for the       long-term success of HBV therapy."                                                       

                           

Viread for HBV was approved by the U.S. Food and Drug Administration       (FDA) in 2008 and has since become the most-prescribed medicine for       chronic HBV in the United States. These five-year data have been       submitted to the FDA and to the European Medicines Agency for review and       potential inclusion in the Viread label.                                                       

                           

About Studies 102 and 103                                                       

                           

Studies 102 and 103 were both multi-center, randomized, double-blind       Phase 3 clinical trials comparing Viread to Hepseraamong       HBeAg-negative (Study 102; n=375) and HBeAg-positive (Study 103; n=266)       chronic hepatitis B patients with compensated liver disease. Patients       had HBV DNA above 100,000 copies/mL and elevated levels of alanine       aminotransferase (ALT, an enzyme that serves as a measure of liver       inflammation) upon study initiation. The majority of patients were       treatment-naive.                                                       

                           

Patients originally randomized to Hepsera in both studies rolled over to       open-label Viread treatment (n=196) at week 48, while patients       originally randomized to Viread continued open-label Viread (n=389). All       patients were asked to undergo liver biopsy at 48 weeks of treatment and       again at five years of treatment, and a total of 331 patients were       evaluated in the histology analysis.                                                       

                           

Seventy-two percent of patients in Study 102 and 50 percent of patients       in Study 103 achieved normalized ALT at week 240. Viread was       well-tolerated in both studies. The most commonly observed adverse       events were abdominal pain, nasopharyngitis, headache, influenza, back       pain and hypertension. Across both studies, 2.1 percent of patients who       received Viread for five years discontinued treatment due to an adverse       event and 0.9 percent of patients experienced a confirmed increase in       serum creatinine of at least 0.5 mg/dL or calculated creatinine       clearance less than 50 mL/min.                                                       

                           

Important Information About Viread for Chronic       Hepatitis B                                                       

                           

Viread (tenofovir disoproxil fumarate) is indicated for the treatment of       chronic hepatitis B in adults. The following points should be considered       when initiating therapy with Viread for the treatment of HBV infection:       This indication is based primarily on data from the treatment of       nucleoside-treatment-naive patients, and a smaller number of patients       who had previously received lamivudine or adefovir. Patients were adults       with HBeAg-positive and HBeAg-negative chronic hepatitis B with       compensated liver disease. Viread was evaluated in a limited number of       subjects with chronic hepatitis B and decompensated liver disease. The       number of patients in clinical trials who had lamivudine- or       adefovir-associated substitutions at baseline was too small to reach       conclusions of efficacy.                                                       

                           

Lactic acidosis and severe hepatomegaly with steatosis, including fatal       cases, have been reported with the use of nucleos(t)ide analogs,       including Viread, in combination with other antiretrovirals.                                                       

                           

Severe acute exacerbations of hepatitis have been reported in       HBV-infected patients who have discontinued anti-hepatitis B therapy,       including Viread. Hepatic function should be monitored closely with both       clinical and laboratory follow-up for at least several months in       patients who discontinue anti-hepatitis B therapy, including Viread. If       appropriate, resumption of anti-hepatitis B therapy may be warranted.                                                       

                           

New onset or worsening of renal impairment including cases of acute       renal failure and Fanconi syndrome has been reported with the use of       Viread. It is recommended to assess creatinine clearance (CrCl) before       initiating treatment with Viread and monitor CrCl and serum phosphorus       in patients at risk, including those who have previously experienced       renal events while receiving Hepsera. Administering Viread with       concurrent or recent use of nephrotoxic drugs should be avoided.                                                       

                           

Viread should not be used with other tenofovir-containing products       (e.g., Atripla(R), Complera(R), Truvada(R)).       Viread should not be administered in combination with Hepsera.                                                       

                           

Due to the risk of development of HIV-1 resistance, Viread should only       be used as part of an appropriate antiretroviral combination regimen in       HIV-infected patients with or without HBV coinfection. HIV antibody       testing should be offered to all HBV-infected patients before initiating       therapy with Viread.                                                       

                           

Decreases in bone mineral density (BMD) have been observed in       HIV-infected patients. It is recommended that BMD monitoring be       considered for patients with a history of pathologic fracture or who are       at risk for osteopenia. The bone effects of Viread have not been studied       in patients with chronic HBV infection. Cases of osteomalacia       (associated with proximal renal tubulopathy and which may contribute to       fractures) have been reported in association with the use of Viread.                                                       

                           

In controlled clinical trials in patients with chronic hepatitis B with       compensated liver disease, the most common adverse reaction (all grades)       was nausea, observed in 9 percent of patients taking Viread at week 48.       Other adverse reactions observed at week 48 in greater than 5 percent of       patients treated with Viread include abdominal pain, diarrhea, headache,       dizziness, fatigue, nasopharyngitis, back pain and skin rash.                                                       

                           

In HBV-infected patients with decompensated liver disease, the most       common adverse reactions (all grades) reported in greater-than or equal       to 10 percent of patients treated with Viread were abdominal pain (22       percent), nausea (20 percent), insomnia (18 percent), pruritus (16       percent), vomiting (13 percent), dizziness (13 percent), and pyrexia (11       percent).                                                       

                           

Coadministration of Viread with didanosine increases didanosine       concentrations. Use with caution and monitor for evidence of didanosine       toxicity (eg, pancreatitis, neuropathy). Didanosine should be       discontinued in patients who develop didanosine-associated adverse       reactions. In adults weighing >60 kg, the didanosine dose should be       reduced to 250 mg when it is coadministered with Viread. Data are not       available to recommend a dose adjustment of didanosine for patients       weighing <60 kg. Coadministration of Viread with atazanavir decreases       atazanavir concentrations and increases tenofovir concentrations. Use       atazanavir with Viread only with additional ritonavir; monitor for       evidence of tenofovir toxicity. Coadministration of Viread with       lopinavir/ritonavir increases tenofovir concentrations. Monitor for       evidence of tenofovir toxicity.                                                       

                           

The recommended dose for the treatment of chronic hepatitis B is 300 mg       once daily taken orally without regard to food. The dosing interval of       Viread should be adjusted and renal function closely monitored in       patients with moderate and severe renal impairment.                                                       

                           

The parent compound of Viread was discovered through a collaborative       research effort between Dr. Antonin Holy, Institute for Organic       Chemistry and Biochemistry, Academy of Sciences of the Czech Republic       (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical       Research, Katholic University in Leuven, Belgium.                                                       

                           

Please see full Prescribing Information for Viread, Complera, Truvada       and Hepsera (including BOXED WARNINGS).                                                       

                           

About Gilead Sciences                                                       

                           

Gilead Sciences is a biopharmaceutical company that discovers, develops       and commercializes innovative therapeutics in areas of unmet medical       need. The company's mission is to advance the care of patients suffering       from life-threatening diseases worldwide. Headquartered in Foster City,       California, Gilead has operations in North America, Europe and Asia       Pacific.                                                       

                           

Forward-Looking Statement                                                       

                           

This press release includes forward-looking statements, within the       meaning of the Private Securities Litigation Reform Act of 1995, that       are subject to risks, uncertainties and other factors, including the       risks that the FDA and the European Medicines Agency may not agree to       the inclusion of the five-year data in the Viread label. In addition,       the data may not impact physicians' decisions to prescribe Viread over       other existing or future HBV medications. In addition, as Viread is used       over longer periods of time by many patients with underlying health       problems, taking numerous other medicines, safety, resistance, drug       interaction or other issues may arise, which could reduce the market       acceptance of Viread. These risks, uncertainties and other factors could       cause actual results to differ materially from those referred to in the       forward-looking statements. The reader is cautioned not to rely on these       forward-looking statements. These and other risks are described in       detail in Gilead's Quarterly report on Form 10-Q for the quarter ended       June 30, 2011, as filed with the U.S. Securities and Exchange       Commission. All forward-looking statements are based on information       currently available to Gilead, and Gilead assumes no obligation to       update any such forward-looking statements.                                                       

                           

U.S. full prescribing information for Viread is available at  www.Viread.com    .                                                       

                           

U.S. full prescribing information for Hepsera is available at  www.Hepsera.com    .                                                       

                           

Complera, Hepsera, Truvada and Viread are registered trademarks of       Gilead Sciences, Inc. or its related companies.                                                       

                           

Atripla is a registered trademark of Bristol-Myers Squibb & Gilead       Sciences, LLC.                                                       

                           

For more information on Gilead Sciences, please visit the company's       website at  www.gilead.com           or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.                                                       

                           

SOURCE: Gilead Sciences, Inc.                                                       

                                            Gilead Sciences, Inc.         Susan Hubbard, 650-522-5715 (Investors)         Soleil Harrison, 650-522-5283 (Media)        

StephenW

Patients at Risk for Hepatitis B Are Not Adequately Screened Before Receiving Chemotherapy Leading to the Preventable Reactivation of Hepatitis B Infection乙型肝炎风险的患者在接受化疗，导致预防乙肝病毒感染再激活之前没有充分检查.

                                Presented: Monday, November 7, 3:45 pm                                                                                                  
                                             
                           
                           

SAN FRANCISCO, Nov. 7, 2011 /PRNewswire via COMTEX/ --By examining 70,737 patients through institutional databases and medical charts, researchers at The University of Texas MD Anderson Cancer Center determined that only 20 percent of patients with newly diagnosed cancer who had hepatitis B virus (HBV) risk factors were screened for HBV infection before starting chemotherapy. This amount of screening is inadequate, according to Jessica P. Hwang, MD, MPH, the lead author of the study, "I hope my study results will increase awareness among medical providers so that they will actively screen for hepatitis B viral infection to prevent poor outcomes for these patients after their chemotherapy."                                                       

                           

For patients with HBV infection, the danger is that their hepatitis B virus can be reactivated by chemotherapy. While those with reactivated HBV infection can be treated with antiviral therapy, initiating antiviral prophylaxis prior to chemotherapy can prevent reactivation. Using well-known HBV risk factors, a greater percentage of cancer patients with HBV infection can be accurately identified and successfully treated before starting chemotherapy.                                                       

                           

Unfortunately, reactivation is common and may have occurred in nearly 25 percent of all patients with HBV who were newly diagnosed with cancer and received chemotherapy. This reactivation of HBV infection is preventable with screening and antiviral prophylaxis prior to the onset of chemotherapy. The study's conclusion clearly states that screening and prophylactic treatment of HBV infection prior to chemotherapy could reduce mortality in cancer patients with HBV.                                                       

                           

"Reactivation is preventable and depends only on accurate screening and prophylaxis. For medical providers to practice effective screening, data-driven policies and strong collaboration among oncology and hepatology communities are essential," concludes Dr. Hwang.                                                       

                           

Abstract title:                                                       

                           

Reactivation of Hepatitis B Infection Among Patients with Cancer                                                       

                           

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in San Francisco, California, November 4 - 8, will bring together more than 8,000 researchers from 55 countries.                                                       

                           

A press room will be available from November 5 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.                                                       

                           

Press releases and all abstracts are available online at  www.aasld.org    .                                                       

                           

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit  http://www.XpressPress.com    .                                                       

                           

SOURCE  American Association for the Study of Liver Diseases (AASLD)                                                       

                            Copyright (C) 2011 PR Newswire. All rights reserved                    

StephenW

Health of Patients with Nonalcoholic Steatohepatitis Improved Through Treatment with Anti-CD3 Antibodies  Presented: Monday, November 7, 8:30 am  Share
  


      By American Association for the Study of Liver Diseases (AASLD)

        Published: Monday, Nov.  7, 2011 -  4:54 am

通过抗CD3抗体治疗非酒精性脂肪性肝炎患者的健康改进

更多：http://www.sacbee.com/2011/11/07/4035574/health-of-patients-with-nonalcoholic.html＃ixzz1d5WcFE5Q


                 SAN FRANCISCO, Nov. 7, 2011 --     /PRNewswire/ -- Nonalcoholic steatohepatitis (NASH) is a major cause of cirrhosis and is growing in incidence in the United States. By treating patients with NASH with orally administered anti-CD3 monoclonal antibodies, researchers at Hadassah Medical Center and NasVax Ltd in Israel were able to improve clinical biomarkers for insulin resistance as well as liver enzyme levels.
The presentation of the study at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (Monday, November 7), is on the results of a phase IIa blinded, placebo-controlled trial. Previous studies in animal models showed improvement in inflammation and autoimmunity. The purpose of this clinical trial was to determine safety and trends in clinical biomarkers and immune-modulation in patients with NASH.
The 36 subjects received one of three dosage levels of oral antibody immunotherapy or placebo once daily for 30 days, followed by an additional 30 days of observation. In addition to assessing a broad range of safety parameters, patients were tested for liver enzymes, glucose, lipid profile, oral glucose tolerance, serum cytokines, and regulatory T cells. Treatment was safe and very well tolerated, and no treatment-related adverse events were noted for any of the patients.   
         Because of the positive results of the study, lead researcher Dr. Mizrahi, said, "We think that these data are promising for the treatment of inflammatory diseases. The mechanism of action, which is the induction of regulatory T cells for the suppression of inflammation, is distinct from other therapies that have been investigated to date. Consequently we have intensified our effort to progress further clinical development in NASH and complete the ongoing Phase IIa trial in Hepatitis C."
Abstract title:
Oral administration of anti-C03 MAb to patients with NASH is safe, promotes regulatory T cells, decreases liver enzymes, and alleviates insulin resistance: Results of a phase IIA blinded placebo-controlled trial
Oral administration of anti-C03 MAb to patients with NASH is safe, promotes regulatory T cells, decreases liver enzymes, and alleviates insulin resistance: Results of a phase IIA blinded placebo-controlled trial
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in San Francisco, California, November 4 – 8, will bring together more than 8,000 researchers from 55 countries.
A press room will be available from November 5 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.
Press releases and all abstracts are available online at www.aasld.org.
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.
SOURCE  American Association for the Study of Liver Diseases (AASLD)        


Read more: http://www.sacbee.com/2011/11/07/4035574/health-of-patients-with-nonalcoholic.html#ixzz1d5WK2jSf

StephenW

Novartis presents alisporivir phase II data results at AASLD Congress
Basel
Monday, November 07, 2011, 15:50 Hrs  [IST]

Novartis presents 12-week results from its new phase II data of alisporivir at the Association for the Study of the Liver (AASLD) Congress in San Francisco, US.  The data shows that first-in-class DEB025 (alisporivir) may produce early viral elimination (or clearance) in interferon-free regimens (as monotherapy or with ribavirin), in previously untreated patients infected with the hepatitis C virus (HCV) genotypes 2 and 3. The company also presented new data on the compound's unique mode of action and high barrier to resistance in previously untreated patients infected with the HCV genotype 1.
诺华公司提出了12个星期的新阶段的alisporivir第二肝（AASLD）大会在美国旧金山，研究协会的数据结果。数据显示，第一级DEB025（alisporivir）可能会产生在以前未经治疗的患者与丙型肝炎病毒（HCV）基因型2感染的早期病毒消除干扰素疗法（或清除）（单药或与利巴韦林），和3。该公司还介绍了该化合物的独特模式的行动，并在以前未经治疗的患者感染丙型肝炎病毒基因型1的抵抗高阻隔新的数据。

Almost half the patients (49%) in the study on DEB025 plus ribavirin achieved viral clearance (negative HCV RNA) as early as week six. One third of patients (32%) receiving DEB025 alone also achieved viral clearance after six weeks. In addition, 97% of patients with viral clearance who continued to receive interferon-free DEB025 plus ribavirin maintained this viral clearance up to week 12. Achieving an early viral clearance is considered one of the most important predictors of sustained viral response, also known as viral cure. After genotype 1, genotypes 2 and 3 are the second most prevalent forms of HCV worldwide.

"Hepatitis C is difficult to treat and newly licensed direct-acting antivirals are not indicated for genotypes 2 and 3 patients, and may leave these patients without new treatment options and with no improvement in tolerability over interferon plus ribavirin, the standard of care", said Professor Jean-Michel Pawlotsky, Department Head of Virology at the Hôpital Henri Mondor, Créteil, France, and the study's principal investigator. "These positive results suggest that DEB025 may be a valuable future treatment option either alone or in combination regimens, providing physicians with flexibility in the treatment process along with favourable tolerability and a high barrier to resistance."

DEB025 is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the virus directly, DEB025 is a host targeting antiviral that targets host proteins essential for the replication of all types of HCV. As a result, DEB025 may offer an effective treatment option across HCV genotypes, with a high barrier to resistance.

"Hepatitis C remains a major public health problem with significant challenges of treatment resistance and poor tolerability," said John Hohneker, Global Head of Development for Integrated Hospital Care at Novartis. "Novartis is committed to providing healthcare professionals with innovative and effective treatments that can help them tackle this global epidemic."

More than 170 million people worldwide are infected with HCV, representing nearly 3% of the world's population. The hepatitis C virus causes serious liver disease, leading to cirrhosis, liver cancer and, in some cases, death.

A pivotal phase III study with DEB025 is ongoing to evaluate the efficacy and safety of DEB025 plus interferon and ribavirin in previously untreated HCV genotype 1 patients. Other phase II trials are ongoing in other patient populations, i.e., genotype 1 experienced patients.

Novartis licensed DEB025 from Debiopharm Group, an independent biopharmaceuticals company based in Switzerland, under an agreement that gives Novartis exclusive worldwide development, manufacturing and marketing rights (excluding Japan).
  

StephenW

Positive Interim Results from Interferon-Free Phase 2b SOUND-C2 Study with Boehringer Ingelheim's Two Investigational HCV Direct Acting Antivirals Presented at AASLD
Planned interim analysis shows up to 76 percent of patients achieved a viral response through 12 weeks of treatment with BI 201335 plus BI 207127 and ribavirin
干扰素- 2b期的声音C2与勃林格殷格翰的两个研究性丙型肝炎病毒直接作用于肝病学会主办抗病毒药物的研究正中期业绩
计划的初步分析显示，76％的患者达到201335加与BI BI的207127和利巴韦林治疗12周，一个病毒的反应

SAN FRANCISCO and RIDGEFIELD, Conn., Nov. 7, 2011 /PRNewswire via COMTEX/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced results from a planned interim analysis of a Phase 2b study, SOUND-C2, that showed the combination of two oral direct acting hepatitis C virus (HCV) compounds - the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127 with ribavirin (RBV) - was successful in reducing viral load below the lower limit of quantifiable levels at week 12 (viral response) in the majority of treatment-naive patients infected with chronic genotype-1 (GT1) HCV. None of the five study arms included treatment with interferon. These data were presented as a late-breaking poster at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, CA.

"Results from the planned interim analysis of SOUND-C2 are encouraging," said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. "They show that BI 201335 plus BI 207127 with ribavirin suppressed the hepatitis C virus to undetectable levels in the majority of patients in this study. We must now complete the study to confirm if this interferon-free regimen leads to a sustained viral response."

"BI is developing our dual oral direct acting antiviral treatment regimen with the goal of eliminating interferon from HCV treatment. We are excited by these interim results and look forward to final study outcomes," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We also are pleased to present other data from our hepatitis C virus portfolio that underscores our ongoing focus on real-world challenges faced by HCV patients, including traditionally difficult-to-treat populations."

The interferon-free oral combination therapy arms with BI 201335, BI 207127 and RBV showed high virologic response rates through week 12 across treatment arms. Viral suppression also was observed in the RBV-sparing arm but was lower than in the other arms at week 12.

76 percent of patients who received BI 201335 once daily (QD) plus BI 207127 twice daily (BID) with RBV achieved viral response through week 12.

70 percent of patients who received BI 201335 QD plus BI 207127 three times daily (TID) with RBV achieved viral response through week 12.

57 percent of patients who received BI 201335 QD plus BI 207127 TID without RBV achieved viral response through week 12.

Breakthrough occurred in 13 percent of patients in BI 201335 plus BI 207127 TID with RBV treatment groups (arms one - three) and in 21 percent of patients in the BI 201335 plus BI 207127 BID with RBV treatment group. Breakthrough occurred in 15 percent of patients in the group that did not receive RBV.

The most frequent adverse events (AEs) were asthenia, pruritus, rash, photosensitivity, jaundice, nausea, vomiting and diarrhea. Across all treatment groups, 6-12 percent of patients discontinued due to AEs.

Results from this open-label, randomized, Phase 2b study were presented as a late-breaking poster titled, "Virologic Response to an Interferon-Free Regimen of BI 201335 and BI 207127, with and Without Ribavirin, in Treatment-Naive Patients with Chronic Genotype-1 HCV Infection: Week 12 Interim Results of the SOUND-C2 Study," by Stefan Zeuzem. In the study, 362 treatment-naive GT1 HCV patients were randomized to receive either:

BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 16 weeks;

BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 28 weeks;

BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 40 weeks;

BI 201335 120 mg QD plus BI 207127 600 mg BID plus RBV for 28 weeks; or

BI 201335 120 mg QD plus BI 207127 600 mg TID without RBV for 28 weeks.

Other BI data being presented at the meeting include:

SILEN-C3: Treatment for 12 or 24 Weeks with BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin (P/R) in Treatment-Naive Patients with Chronic Genotype-1 HCV Infection (Abstract 36. D. Dieterich, et al. November 6, 4:15 p.m. - 4:30 p.m. PT)

Characterization of HCV NS3 Variants that Emerged During Virologic Breakthrough and Relapse from BI 201335 Phase 2 SILEN-C1 Study (Poster 1339. G. Kukolj, et al. November 7, 8:00 a.m. - 5:00 p.m. PT)

Treatment with the Second Generation HCV Protease Inhibitor BI 201335 Results in High and Consistent SVR Rates - Results from SILEN-C1 in Treatment-Naive Patients Across Different Baseline Factors (Abstract 226. M.S. Sulkowski, et al. November 8, 8:45 a.m. - 9:00 a.m. PT)

High Sustained Virologic Response Following Interferon-Free Treatment of Chronic HCV GT1 Infection for Four Weeks with HCV Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127 and Ribavirin, Followed by BI 201335 and PegIFN/Ribavirin - the SOUND-C1 Study (Abstract 249. S. Zeuzem, et al. November 8, 11:15 a.m. - 11:30 a.m. PT)

About Hepatitis C Virus

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease, transplant and failure that affects as many as 175 million people globally, with three to four million new infections occurring each year. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. Chronic HCV infection is the cause of an estimated 8,000 to 10,000 deaths annually in the United States. The majority - about 75 to 85 percent - of HCV cases will develop into chronic infection. It is estimated 20 percent of patients with chronic HCV will develop cirrhosis within 20 years of infection. The mortality rate after cirrhosis has developed is 2 - 5 percent per year.

About Boehringer Ingelheim in Hepatitis C Virus

Boehringer Ingelheim has a long-standing commitment to virology, including developing innovative therapies for HIV/AIDS and HCV. The company recognizes the significance of the HCV epidemic and continues to work on improving treatment and cure rates for diverse populations of HCV patients through its dedicated HCV treatment development program, called HCVerso(TM).

Boehringer Ingelheim is advancing BI 201335, an investigational oral HCV NS3/4A protease inhibitor that has the potential to improve cure rates as compared to PegIFN/RBV therapy. A multi-study Phase 3 trial program currently is underway to evaluate BI 201335 combined with PegIFN/RBV in both treatment-naive and -experienced patients with chronic genotype-1 HCV.

Boehringer Ingelheim also is developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has the potential to eliminate interferon from HCV treatment when combined with BI 201335 and RBV. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, with and without RBV, are currently underway.

About Boehringer Ingelheim Pharmaceuticals, Inc.

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 145 affiliates and more than 42,000 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.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus .

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

StephenW

press release               
Nov. 8, 2011, 11:00 a.m. EST                                Phase IIIb Comparison of BARACLUDE(R) (entecavir) Monotherapy Versus BARACLUDE Plus Tenofovir Combination Shows No Statistical Difference Between Study Arms  96-week study in a population of nucleos(t)ide-naive patients with chronic hepatitis B (CHB) infection
第IIIb期BARACLUDE的（R）（恩替卡韦）单药治疗对战BARACLUDE的加替诺福韦组合的对比表明之间没有统计差异研究组核苷（酸）IDE天真与慢性乙型肝炎（CHB）感染患者的人口在96周的研究.

         
                                  
                                             
                           

   

                                                        

                           

SAN FRANCISCO, Nov 08, 2011 (BUSINESS WIRE) ----Data presented at the American Association for the Study of Liver Diseases congress in San Francisco                                                        

                           

Bristol-Myers       Squibb Company                                                                 BMY                        -0.48%                                 today announced 96-week results from the       BE-LOW(TM) study, a Phase IIIb clinical trial comparing       BARACLUDE monotherapy (0.5mg once daily) with BARACLUDE (0.5mg once       daily) plus tenofovir (300mg once daily) in treatment-naive adult       patients with HBeAg-positive and HBeAg-negative chronic hepatitis B       (CHB) with compensated liver disease. In this study, no statistically       significant difference was observed between the two treatment arms in       the primary efficacy endpoint of HBV DNA <50 IU/mL (approximately 300       copies per mL)(1) at 96 weeks: 76.4% in the BARACLUDE       monotherapy arm and 83.2% in the BARACLUDE plus tenofovir arm       (p=0.0882). Overall, both study arms had similar safety profiles.       Serious adverse events (SAEs) in this study were reported in 6.6%       (12/182) of patients in the BARACLUDE monotherapy arm and in 7.1%       (14/197) of patients in the BARACLUDE plus tenofovir arm. These data       were reported today at the 62nd annual meeting of the American       Association for the Study of Liver Diseases (AASLD) in San Francisco,       California (Abstract #223, presented orally during the Presidential       Plenary Session on Viral Hepatitis).                                                        

                           

"In these 96-week data comparing entecavir monotherapy to combination of       entecavir plus tenofovir, we found that combination therapy did not       result in statistically significant difference in virologic response       compared to entecavir monotherapy. The BE-LOW study data confirmed the       results of previous studies showing limited or no benefit of combination       therapy compared to monotherapy for treatment-naive patients with       chronic hepatitis B," said principal investigator Anna Lok, MD, FRCP,       director of clinical hepatology and professor in the department of       internal medicine at the University of Michigan Medical School in Ann       Arbor.                                                        

                           

Study Results                                                        

                           

In this study, 379 nucleos(t)ide-naive patients with CHB were randomized       to receive either BARACLUDE (entecavir) 0.5 mg once daily (n=182) or       BARACLUDE 0.5 mg plus tenofovir 300 mg once daily (n=197). Key findings       at week 96 are:                                                        

                           

--        A comparable proportion of patients in both treatment arms achieved         the primary efficacy endpoint of HBV DNA <50 IU/mL at 96 weeks: 76.4%         (139/182) in the BARACLUDE monotherapy arm and 83.2% (164/197) in the         BARACLUDE plus tenofovir arm (p=0.0882).                                                        

                           

--        Among HBeAg-positive patients, the proportion achieving HBV DNA <50         IU/mL was 69.8% (88/126) in the BARACLUDE monotherapy arm versus 80.4%         (111/138) in the BARACLUDE plus tenofovir arm (p=0.0460). Further         analysis suggested that this difference could be accounted for by the         subset of patients with a high baseline viral load. Among those         HBeAg-positive patients with a baseline viral load <10(8)         IU/mL, 83% achieved HBV DNA <50 IU/mL in both treatment arms         (BARACLUDE monotherapy 39/47; BARACLUDE plus tenofovir 44/53; p=ns).         However, for those with a baseline viral load greater-than or equal to 10(8) IU/mL,         62% (49/79) of the patients in the BARACLUDE monotherapy arm and 78.8%         (67/85) of the patients in the BARACLUDE plus tenofovir arm achieved         HBV DNA <50 IU/mL.                                                        

                           

--        Among HBeAg-negative patients, the proportion achieving HBV DNA <50         IU/mL was 91.1% (51/56) in the BARACLUDE monotherapy arm versus 89.8%         (53/59) in the BARACLUDE plus tenofovir arm.                                                        

                           

Secondary efficacy endpoints measured in the study included alanine       aminotransferase (ALT) normalization, HBeAg seroconversion, and HBeAg       loss. ALT normalization was observed in 81.9% (149/182) of patients in       this study in the BARACLUDE (entecavir) monotherapy arm versus 69%       (136/197) in the BARACLUDE plus tenofovir arm. HBeAg seroconversion was       observed in 32.5% (41/126) of patients in the BARACLUDE (entecavir)       monotherapy arm versus 21.7% (30/138) in the BARACLUDE plus tenofovir       arm in this study.                                                        

                           

Two patients (1.1%) in the BARACLUDE monotherapy arm compared to five       patients (2.5%) in the BARACLUDE plus tenofovir arm discontinued       treatment prior to week 96. Patients who discontinued therapy prior to       week 96 were considered treatment failures.                                                        

                           

The overall adverse event profiles were similar across study arms. A       total of three deaths occurred among treated patients, all on the       BARACLUDE plus tenofovir arm: one due to bile duct tumor; one due to a       late-onset exacerbation of hepatitis which was associated with       breakthrough viremia while on continued treatment; and one due to       cardiac arrest. One patient (0.5%) in the BARACLUDE monotherapy arm and       two patients (1.0%) in the BARACLUDE plus tenofovir arm experienced on       treatment ALT flares, defined as >2 x baseline ALT and >10 x ULN. No       patients (0.0%) in either arm experienced off-treatment ALT flares. Six       patients (3.3%) in the BARACLUDE monotherapy arm and four (2.0%)       patients in the BARACLUDE plus tenofovir arm experienced serum       creatinine increase greater-than or equal to 0.3 mg/dL. A total of five malignancies occurred       among patients in the study: four (2.2%) patients in the BARACLUDE       monotherapy arm and one (0.5%) patient in the BARACLUDE plus tenofovir       arm. In the BARACLUDE monotherapy arm, there were three diagnoses of       hepatocellular carcinoma (two on-treatment and one off-treatment) and       one case of gastric cancer. In the BARACLUDE plus tenofovir arm there       was one case of breast cancer.                                                        

                           

Two patients (1.0%) in the BARACLUDE monotherapy arm and seven patients       (3.6%) in the BARACLUDE plus tenofovir arm experienced virologic       breakthrough. No recognized genotypic resistance mutations were observed       in either treatment arm.                                                        

                           

About The Study                                                        

                           

The BE-LOW study is an open-label, multicenter, Phase IIIb study of 379       nucleos(t)ide-naive patients with CHB. The patients were randomized 1:1       and treated with either BARACLUDE 0.5 mg once daily (n=182) or BARACLUDE       0.5 mg plus tenofovir 300 mg once daily (n=197). Nucleos(t)ide-naive,       HBeAg-negative CHB patient enrollment was capped at 30%. The primary       efficacy endpoint was the proportion of patients with HBV DNA <50 IU/mL       at week 96.                                                        

                           

About Chronic Hepatitis B                                                        

                           

Approximately 350 million people worldwide are chronically infected with       hepatitis B (approximately 5% of the world's population) and 75% of       these cases occur in the Asia-Pacific region. Most people with chronic       hepatitis B show no signs or symptoms, so many of those chronically       infected are unaware of their status. A blood test can diagnose chronic       hepatitis B. Patients should speak with their doctor about options       available for this condition.                                                        

                           

About BARACLUDE (entecavir)                                                        

                           

BARACLUDE, a nucleoside analogue discovered at Bristol-Myers Squibb, was       first approved by the U.S. Food and Drug Administration in March 2005       for use in adult chronic hepatitis B patients with compensated liver       disease. The initial approval was based on histologic, virologic,       biochemical, and serologic responses in nucleoside-treatment-naive and       lamivudine-resistant adult subjects with HBeAg-positive or       HBeAg-negative CHB infection and compensated liver disease. BARACLUDE is       also indicated for use for the treatment of chronic hepatitis B in adult       patients with decompensated liver disease based on virologic,       biochemical, serologic, and safety data.                                                        

                           

INDICATION and IMPORTANT SAFETY INFORMATION       about BARACLUDE (entecavir) Tablets:                                                        

                           

INDICATION                                                        

                           

BARACLUDE is indicated for the treatment of chronic hepatitis B virus       (HBV) infection in adults with evidence of active viral replication and       either evidence of persistent elevations in serum aminotransferases (ALT       or AST) or histologically active disease.                                                        

                           

The following points should be considered when initiating BARACLUDE       (entecavir):                                                        

                           

--        This indication is based on histologic, virologic, biochemical, and         serologic responses in nucleoside-treatment-naive and         lamivudine-resistant adult subjects with HBeAg-positive or         HBeAg-negative chronic HBV infection and compensated liver disease.                                                        

                           

--        Virologic, biochemical, serologic, and safety data are available from         a controlled study in adult subjects with chronic HBV infection and         decompensated liver disease.                                                        

                           

--        Virologic, biochemical, serologic, and safety data are available for a         limited number of adult subjects with HIV/HBV co-infection who have         received prior lamivudine therapy.                                                        

                           

IMPORTANT SAFETY INFORMATION                                                        

                           

WARNINGS: SEVERE ACUTE EXACERBATIONS OF HEPATITIS B, PATIENTS       CO-INFECTED WITH HIV AND HBV, and LACTIC ACIDOSIS AND HEPATOMEGALY                                                        

                           

--        Severe acute exacerbations of hepatitis B have been reported in         patients who have discontinued anti-hepatitis B therapy, including         entecavir. Hepatic function should be monitored closely with both         clinical and laboratory follow-up for at least several months in         patients who discontinue anti-hepatitis B therapy. If appropriate,         initiation of anti-hepatitis B therapy may be warranted.                                                        

                           

--        Limited clinical experience suggests there is a potential for the         development of resistance to HIV (human immunodeficiency virus)         nucleoside reverse transcriptase inhibitors if BARACLUDE (entecavir)         is used to treat chronic HBV infection in patients with HIV infection         that is not being treated. Therapy with BARACLUDE is not recommended         for HIV/HBV co-infected patients who are not also receiving highly         active antiretroviral therapy (HAART).                                                        

                           

--        Lactic acidosis and severe hepatomegaly with steatosis, including         fatal cases, have been reported with the use of nucleoside analogues,         alone or in combination with antiretrovirals.                                                        

                           

Warnings and Precautions                                                        

                           

--        Before initiating BARACLUDE (entecavir) therapy, HIV antibody testing         should be offered to all patients. BARACLUDE has not been studied as a         treatment for HIV infection and is not recommended for this use.                                                        

                           

--        Lactic acidosis with BARACLUDE use has been reported, often in         association with hepatic decompensation, other serious medical         conditions, or drug exposures. Patients with decompensated liver         disease may be at higher risk for lactic acidosis. BARACLUDE should be         suspended in any patient who develops clinical or laboratory findings         suggestive of lactic acidosis or pronounced hepatotoxicity.                                                        

                           

Adverse Reactions                                                        

                           

--        In clinical trials in patients with compensated liver disease, the         most common (greater-than or equal to 3%) adverse reactions of any severity with at least a         possible relation to study drug for BARACLUDE-treated subjects were         headache, fatigue, dizziness, and nausea. In these trials, the most         common adverse reactions of moderate to severe intensity (grades 2-4)         were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache,         dizziness, somnolence, and insomnia.                                                        

                           

--        In the decompensated liver disease trial, the most common adverse         reactions of any severity among patients treated with BARACLUDE,         regardless of causality, included: peripheral edema (16%), ascites         (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper         respiratory infection (10%). In this trial, 18% (18/102) of BARACLUDE         patients and 20% (18/89) of adefovir patients died during the first 48         weeks of therapy. The majority of those deaths were due to liver         related causes.                                                        

                           

Drug Interactions                                                        

                           

BARACLUDE is primarily eliminated by the kidneys, therefore       coadministration of BARACLUDE with drugs that reduce renal function or       compete for active tubular secretion may increase serum concentrations       of either entecavir or the coadministered drug. Patients should be       monitored closely when receiving BARACLUDE with other renally-eliminated       drugs.                                                        

                           

Pregnancy and Nursing Mothers                                                        

                           

--        There are no adequate and well-controlled studies of BARACLUDE         (entecavir) in pregnant women. BARACLUDE should be used during         pregnancy only if clearly needed and after careful consideration of         the risks and benefits.                                                        

                           

--        There are no studies on the effect of BARACLUDE on transmission of HBV         from mother to infant. Therefore, appropriate interventions should be         used to prevent neonatal acquisition of HBV.                                                        

                           

--        It is not known whether BARACLUDE is excreted into human milk;         however, many drugs are excreted into breast milk. Due to the         potential for serious adverse reactions in nursing infants from         BARACLUDE, risks and benefits should be considered when deciding         whether to discontinue breast-feeding or discontinue BARACLUDE in         nursing women.                                                        

                           

Pediatric Use                                                        

                           

--        Safety and effectiveness of BARACLUDE in pediatric patients below the         age of 16 years have not been established.                                                        

                           

Renal Impairment                                                        

                           

--        Dosage adjustment of BARACLUDE is recommended for patients with a         creatinine clearance <50 mL/min, including those on hemodialysis or         continuous ambulatory peritoneal dialysis.                                                        

                           

--        The safety and efficacy of BARACLUDE in liver transplant recipients         are unknown. Renal function must be carefully monitored both before         and during treatment with BARACLUDE in a liver transplant recipient         who has received or is receiving an immunosuppressant that may affect         renal function, such as cyclosporine or tacrolimus.                                                        

                           

Dosage and Administration                                                        

                           

BARACLUDE should be administered on an empty stomach (at least 2 hours       after a meal and at least 2 hours before the next meal).                                                        

                           

The recommended dose of BARACLUDE (entecavir):                                                        

                           

--        in nucleoside-naive adults and adolescents (16+ yrs) with compensated         liver disease is 0.5 mg once daily                                                        

                           

--        in adults and adolescents (16+ yrs) with compensated liver disease,         and refractory to lamivudine or with known lamivudine or telbivudine         resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or         rtV173L) is 1 mg once daily                                                        

                           

--        in adults with decompensated liver disease is 1 mg once daily                                                        

                           

The optimal duration of treatment with BARACLUDE for patients with       chronic HBV infection and the relationship between treatment and       long-term outcomes such as cirrhosis and hepatocellular carcinoma are       unknown.                                                        

                           

Additional Information                                                        

                           

BARACLUDE (entecavir) is not a cure for HBV. Patients should be advised       that treatment with BARACLUDE has not been shown to reduce the risk of       transmission of HBV to others through sexual contact or blood       contamination.                                                        

                           

Please see accompanying Full Prescribing Information, including Boxed       WARNINGS, or click       here.                                                        

                           

About Bristol-Myers Squibb                                                        

                           

Bristol-Myers Squibb is a global biopharmaceutical company whose mission       is to discover, develop and deliver innovative medicines that help       patients prevail over serious diseases. For more information, please       visit  http://www.bms.com           or follow us on Twitter at  http://twitter.com/bmsnews    .                                                        

                           

BARACLUDE(R) (entecavir) is a registered trademark of       Bristol-Myers Squibb.                                                        

                                    _________________        (1)    HBV DNA carries the genetic blueprint of the hepatitis B virus.               The number of HBV DNA "copies" found in a person's blood, or               "viral load," indicates how rapidly the virus is reproducing in               their liver. Low levels of HBV DNA, recognized as 300 copies per               milliliter or less, indicate an "inactive" hepatitis B infection.                                    

SOURCE: Bristol-Myers Squibb Company