AASLD-New Data Analyses for VICTRELIS™ (boceprevir) will be Presented By Merck

Industry Updates: Sep 30, 2011

Merck Announces New Data Analyses for VICTRELIS™ (boceprevir) will be Presented at The American Association for the Study of Liver Diseases 2011 Annual Meeting

Source:biowire

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new analyses from Phase III studies of VICTRELIS (boceprevir), the company’s first-in-class, oral hepatitis C virus (HCV) NS3/4A protease inhibitor will be presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The meeting will be held Nov. 4-8 in San Francisco. Presentations will include results from the Phase III PROVIDE study, which evaluated the efficacy of VICTRELIS in combination with peginterferon alfa and ribavirin in adult patients with chronic HCV genotype 1 infection who had prior null response to treatment with peginterferon alfa and ribavirin alone.

More than 30 abstracts highlighting Merck medicines and investigational therapies for chronic HCV will be presented at AASLD, including four oral presentations and 14 posters for VICTRELIS. One poster has been selected as a Presidential Poster of Distinction.

New data also will be presented on the efficacy and safety of Merck's MK-5172, an investigational once-daily, second-generation oral HCV NS3/4A protease inhibitor, in patients chronically infected with HCV genotypes 1 and 3.

"Merck looks forward to sharing data with the scientific community at this year's AASLD to inform the continuing fight against chronic hepatitis C," said Roger J. Pomerantz, M.D., F.A.C.P., senior vice president, Infectious Diseases, Merck Research Laboratories.

The abstracts were published today and can be accessed on the AASLD website. For program information, please visit https://www.aasld.org.

Key presentations for VICTRELIS

Efficacy of Boceprevir in Patients with Null Responses to Peginterferon/Ribavirin:

The PROVIDE study. Vierling, J. et al. Poster 931. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall

Treatment-Naive Black Patients Treated with Boceprevir Combined with Peginterferon Alfa-2b + Ribavirin: Results from HCV SPRINT-2. McCone, J. et al. Poster 981. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m.

Analysis of Resistance-Associated Amino Acid Variants (RAVs) in non-SVR Patients Enrolled in a Retrospective Long-Term Follow-Up Analysis of Boceprevir Phase III Clinical Studies. Barnard, R.J.O. et al. Abstract #164. Oral Presentation: Monday, Nov. 7, 3:15 - 3:30p.m., Moscone West Convention Center, Rooms 2001-2003 and 2014-2016

Genotypic and Phenotypic Correlates of Resistance in HCV Genotype 1a and 1b Infected Patients Treated with Boceprevir Plus Peginterferon Alpha and Ribavirin. Ogert, R.A. et al. Poster 927. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall. Selected as a Presidential Poster of Distinction

Other key Merck presentations

IL28B genotype predicted for >/=1 log10 IU/mL reduction in serum HCV RNA after 4 weeks of peginterferon and ribavirin therapy: implications for the use of the lead-in strategy for DAA-based treatment regimens. Thompson, A.J. et al. Abstract #157. Oral Presentation: Monday, Nov. 7, 3:00 -3:15 p.m., Moscone West Convention Center, Rooms 2006-2008

Safety and Antiviral Activity of MK-5172, a Next Generation HCV NS3/4A Protease Inhibitor with a Broad HCV Genotypic Activity Spectrum and Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients. Petry, A. et al. Poster 346. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall

MK-5172, a Second-Generation HCV NS3/4A Protease Inhibitor, is Active against Common Resistance Associated Variants (RAVs) and Exhibits Cross-Genotype Activity. Graham, D. et al. Poster 370. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall

Indications and usage for VICTRELIS

VICTRELIS was approved by the U.S. Food and Drug Administration (FDA) on May 13 for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection:

  • VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
  • VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors. VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 logHCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 logHCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.
  • Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.

Important safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS.

VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).

Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. Dose reduction of VICTRELIS is not recommended.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Merck's global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov).

Please see Prescribing Information for VICTRELIS at

http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.

AASLD-New Data On BMS-790052 and BMS-650032 to be presented by Bristol-Myers Squibb


September 30, 2011 11:19 AM EDT


Bristol-Myers Squibb to Present New Data Demonstrating Company’s Leadership in Liver Disease at The Liver Meeting® / AASLD Annual Meeting

  • Oral presentation on BARACLUDE® (entecavir) reinforces continued clinical development commitment in hepatitis B
  • Oral presentations on hepatitis C investigational compounds BMS-790052 and BMS-650032 demonstrate advancement of robust pipeline
  • Breadth of data highlights Company’s commitment to pursuing research that aims to improve the management of liver disease

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) announced today that 22 abstracts on the Company’s research in liver disease have been accepted for presentation at The Liver Meeting® 2011, the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco, November 4 - 8. Bristol-Myers Squibb is advancing a portfolio of compounds that has the potential to address unmet medical needs for patients with liver disease, including BARACLUDE® (entecavir) for chronic hepatitis B (CHB), and the investigational compounds BMS-790052, BMS-650032 and PEG-Interferon lambda (Lambda) for hepatitis C (HCV) and brivanib for hepatocellular carcinoma (HCC).

Key presentations include an oral presentation on BARACLUDE monotherapy vs. combination therapy for CHB and two oral presentations of Phase II data on the Company’s investigational HCV direct-acting antivirals (DAAs). These presentations will highlight:

  • The first data from the BE-LOW study, a Phase IIIb comparative study of BARACLUDE plus tenofovir vs. BARACLUDE monotherapy in treatment-naïve adults with CHB
  • The first results from a Phase IIb study of the NS5A replication complex inhibitor BMS-790052 plus peginterferon alfa and ribavirin (alfa/RBV) in treatment-naive HCV genotype 1 and 4 patients, evaluating virologic response through 12 weeks on treatment (eRVR)
  • The first results of a Phase IIa study of the dual DAA regimen of BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected patients who have not responded to prior alfa/RBV therapy (null responders), evaluating sustained virologic response 12 weeks post-treatment (SVR12)

“Bristol-Myers Squibb is at the forefront of innovation in researching the treatment of liver diseases. In hepatitis C, where there remain considerable unmet medical needs, our goal is to increase treatment options for patients by developing a portfolio of compounds with different mechanisms of action,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data we are presenting at the Liver Meeting help to expand our understanding of the potential efficacy and safety profiles of these investigational compounds and support the recent initiation of a broad Phase III development program in HCV.”

The Company will also present new data that further describe the mechanistic and clinical profile of Lambda, and real-world data that add to the understanding of the prevalence of and current treatment patterns in HBV, HCV and HCC, including an oral presentation of data from the BRIDGE study in HCC. The BRIDGE study is designed to develop global understanding of HCC, including assessment of treatment by geography and etiology, and associated clinical outcomes.

The complete list of Bristol-Myers Squibb data presentations is below. Abstracts can be accessed on the AASLD website at http://aasld2011.abstractcentral.com/login.

Abstract Number Title Date/Time
Hepatitis B: BARACLUDE Clinical Data
Oral

#223

Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir (TDF) in nucleos(t)ide-naïve patients with chronic hepatitis B (CHB): the BE-LOW study Presidential Plenary III

Nov. 8

8:00 am PST

Hepatitis B: Outcomes Research / Real-World Data
Poster

#458

Real World Data on Long Term Treatment Initiation in patients with Chronic Hepatitis B: cohort observations in France, Germany, Poland, Romania and Turkey Nov. 5
Poster

#478

Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis Nov. 5
Poster

#481

Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Entecavir versus Tenofovir Nov. 5
Poster

#482

Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Oral Antivirals Recommended by Current Guidelines versus Oral Antivirals Not Recommended by Current Guidelines Nov. 5
Hepatitis C: Direct-Acting Antiviral Data
Oral

#LB-4

Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response (SVR12) in HCV Genotype 1b-Infected Null Responders Nov. 7

3:30 pm PST

Oral

#227

BMS-790052, A NS5A Replication Complex Inhibitor, Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naive HCV-Genotype 1 or 4 Patients: Phase 2b AI444010 Study Interim Week 12 Results Presidential Plenary III

Nov. 8

9:00 am PST

Poster #381 Evaluation of drug interaction potential of the HCV protease inhibitor BMS-650032 at 200mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers Nov. 5
Poster #LB-20 Combination Therapy of Treatment-Naïve and Nonresponder Patients with HCV Genotype 1 Infection with BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alfa-2a and Ribavirin Nov. 7
Poster #LB-22 BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alpha-2b and Ribavirin in Japanese Treatment-Naïve and Nonresponder Patients with Chronic HCV Genotype 1 Infection Nov. 7
Poster #1362 Single-Dose Pharmacokinetics of BMS-790052 in Subjects with Hepatic Impairment Compared With Healthy Subjects Nov. 7
Poster #1340 BMS-790052 Has No Effect on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Healthy Female Subjects Nov. 7
Hepatitis C: PEG-Interferon Lambda Data
Poster #376 The Effect of Pegylated Interferon Lambda on the Expression of Interferon Stimulated Genes in Whole Blood in Chronic Hepatitis C Patients in a Phase 2a Study Nov. 5
Poster #1058 Implementation of an HCV Model for Il-28B Genotype Treatment Duration Optimization and Cure Rate Maximization for Pegylated Interferon Lambda Nov. 6
Poster #1343 Pegylated Interferon Lambda Ameliorates Ribavirin (RBV)-Induced Anemia in HCV Patients by Maintaining Compensatory Erythropoiesis: Analysis of EMERGE Phase 2b Results through Week 12 Nov. 7
Poster #1344 Safety and Efficacy of Pegylated Interferon Lambda (peg-lambda) Compared to Pegylated Interferon α-2a (peg-alfa) in HCV-Infected Patients (G1/2/3) With Compensated Cirrhosis: EMERGE Phase IIB Efficacy and Safety Results through Week 12 Nov. 7
Poster #1363 Less severe flu-like symptoms with PEG-Interferon Lambda in Phase IIb Study of treatment-naive chronic hepatitis C (CHC) patients Nov. 7
Hepatitis C: Epidemiology / Real-World Data
Poster #412 Prevalence of HCV and Host IL28B Genotypes in China Nov. 5
Poster #1045 Adverse Events in Patients With Chronic Hepatitis C Treated With PegIFN-alfa and Ribavirin in Real-World Setting Nov. 6
Poster #1084 Virologic Response among Hepatitis C (HCV) Patients Treated in Clinical Practice Nov. 6
Poster #1736 Single nucleotide polymorphisms near IL28B and IL28A genes are associated with spontaneous seroclearance of HCV RNA in untreated patients with HCV infection Nov. 7
Hepatocellular Carcinoma: Outcomes Research
Oral

#267

Observations of Hepatocellular Carcinoma (HCC) Management Patterns from the Multinational HCC BRIDGE Study: First Overall Analysis of the North American Cohort Nov. 811:15 am PST

INDICATION and IMPORTANT SAFETY INFORMATION about BARACLUDE® (entecavir)

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:

  • This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naïve 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 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 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 (≥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 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:

  • in nucleoside-naïve 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

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 Full Prescribing Information, including boxed WARNINGS, available at www.BARACLUDE.com.

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.

Bristol-Myers Squibb CompanyMedia:Cristi Barnett, 609-252-6028cristi.barnett@bms.comorInvestors:John Elicker, 609-252-4611john.elicker@bms.com

Source: Bristol-Myers Squibb Company

AASLD-Vertex presentation of New Data; INCIVEK™and VX-222

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX - News) today announced that abstracts from its hepatitis C program, including two late-breaking posters from studies of INCIVEK™ (telaprevir) tablets and VX-222, were accepted for presentation at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 4-8, 2011.

New data, including sustained viral response (SVR, or viral cure) results, from a Phase 2 study evaluating short durations of 12- and 24-week regimens of VX-222 in combination with INCIVEK (in-SEE-veck), pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment will be presented for the first time. Additionally, new data from a Phase 2 study evaluating INCIVEK combination treatment in people co-infected with genotype 1 chronic hepatitis C and human immunodeficiency virus (HIV) will be presented at the meeting. All people in this study were new to hepatitis C treatment.

“INCIVEK combination therapy has successfully increased viral cure rates and shortened total treatment time for the majority of people with hepatitis C who are being treated for the first time, but we have more to do,” said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. “Our ongoing research is aimed at further improving treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations, including some without interferon, that may offer higher cure rates and shorter treatment times.”
The accepted abstracts are now available on the AASLD website at https://www.aasld.org/lm2011.

INCIVEK Oral Presentations
1. #31: “Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study.” November 6, 2011, 3:00 p.m. PDT.
2. #32: “Predictors of virologic response with telaprevir-based combination treatment in HCV genotype 1-infected patients with prior peginterferon/ribavirin treatment failure: post-hoc analysis of the Phase III REALIZE study.” November 6, 2011, 3:15 p.m. PDT.
3. #35: “Retreatment with telaprevir/Peg-IFN/RBV after a short exposure to telaprevir in Phase I studies: interim results from a Phase IIIb rollover trial (C219).” November 6, 2011, 4:00 p.m. PDT.
4. #248: “Follow-up of SVR Durability and Viral Resistance in Patients with Chronic Hepatitis C Treated with Telaprevir-Based Regimens: Interim Analysis of the EXTEND Study.” November 8, 2011, 11:00 a.m. PDT.
Vertex Late-Breaking Poster Presentations
1. #LB-8: “Telaprevir Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: 24-Week Treatment Interim Analysis.” November 7, 2011.
2. #LB-14: “VX-222/telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naïve Genotype 1 HCV Patients Treated for 12 Weeks: ZENITH Study, SVR12 Interim Analysis.” November 7, 2011.
Vertex Poster Presentations
1. #943: “Projections Using Decision-Analytic Modeling of Long-Term Clinical Value of Telaprevir for the Treatment of HCV Patients who had Failed Prior Peginterferon/Ribavirin Treatment.” November 6, 2011.
2. #1328: “Summary of Clinical Virology Findings from Clinical Trials of Telaprevir.” November 7, 2011.
3. #1331: “Different likelihood of achieving SVR on a telaprevir-containing regimen among null responders, partial responders and relapsers irrespective of similar responses after a peginterferon/ribavirin 4-week lead-in phase: REALIZE study subanalysis.” November 7, 2011. 4. #1368: “Impact of anemia and ribavirin dose reduction on SVR to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure in the Phase III REALIZE study.” November 7, 2011.
5. #1369: “Impact of insulin resistance on virologic response to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: post-hoc analysis of the REALIZE Phase III study.” November 7, 2011.
6. #2105: “Sustained Virologic Response Rates and Viral Resistance Profiles Were Similar in Patients Treated with a Telaprevir-Based Regimen Regardless of Liver Fibrosis Stage.” November 8, 2011.

About INCIVEK
INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.

Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic®.

About VX-222
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is being evaluated in a Phase 2 study in combination with INCIVEK and ribavirin, with and without pegylated-interferon. Vertex retains worldwide commercial rights to VX-222.

IMPORTANT SAFETY INFORMATION
Indication
INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9

Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding Vertex’s aim to further improve treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations that may offer higher cure rates and shorter treatment times. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, future scientific, clinical, competitive or other market factors may adversely affect the potential for INCIVEK-based therapies and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
(VRTX-GEN)

1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed March 21, 2011.
2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900. 3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed March 21, 2011.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.

AASLD-Acceptance of Four TMC435 Abstracts by Medivir

Medivir Announces Acceptance of Four TMC435 Abstracts for Presentation at the AASLD Meeting


~ Including a Late-breaking Oral Presentation of final analysis of the TMC435 phase 2b PILLAR study ~

30-Sep-11 Medivir AB (OMX: MVIR), a research-based speciality pharmaceutical company focused on infectious diseases, today announces that four abstracts related to its once daily (QD), oral investigational hepatitis C drug TMC435 have been accepted for presentation at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from November 4-8 in San Francisco, USA.The abstracts have been published today and can be accessed on the AASLD website http://www.aasld.org/ (http://www.aasld.org/). In accordance with the AASLD embargo policy, information from the abstracts and the accepted titles only are provided below. TMC435, an investigational hepatitis C NS3/4A protease inhibitor, is being jointly developed by Medivir and Tibotec Pharmaceuticals.At the AASLD meeting, in a Late Breaker Oral Presentation, the final analysis, including SVR24 data, from the phase 2b PILLAR study of TMC435 will be presented.

In this study, treatment-naive patients infected with HCV genotype 1 (G1) were dosed once daily for 24 or 48 weeks with 75mg or 150mg of TMC435 in combination with peginterferon α-2a (PegIFN) and ribavirin (RBV).

A 24 week duration was assigned if HCV RNA levels were <25 IU/mL detectable or undetectable at Week 4 and <25 IU/mL undetectable at Weeks 12, 16, and 20. In the control arm patients were treated for 48 weeks with PegIFN/RBV only.

The primary endpoint of the study was sustained virologic response (SVR) at Week 72.

Significantly higher response rates were observed with TMC435 compared to control.

In TMC435 arms, 79-86% of patients were eligible to complete treatment at Week 24. The incidence of discontinuations, adverse events (AEs, including rash, anemia and neutropenia) and serious AEs were similar in the TMC435 and control arms.

Mild, transient increases in direct and indirect bilirubin, not associated with increases in other hepatic parameters, were observed with TMC435 150 mg. TMC435 150 mg QD for 12 weeks is being pursued in the ongoing global phase 3 trials.

Additionally, there will be three poster presentations at the 2011 AASLD meeting.

The titles for the accepted Abstracts are as follows:Late Breaker Oral Presentation: Monday 7 Nov. 3:45pm:· LB-5.

“TMC435 in combination with peginterferon and ribavirin in treatment-naïve HCV genotype 1 patients: Final analysis of the PILLAR Phase IIb study.” M. Fried; M. Buti; G. J. Dore; R. Flisiak; P. Ferenci; I. M. Jacobson; P. Marcellin; M. P. Manns; I. Nikitin; F. Poordad; M. Sherman; S. Zeuzem; O. Lenz; M. Peeters; V. Sekar; G. De SmedtPoster Presentations:· 1329.

“TMC435 in combination with peginterferon alpha-2a/ribavirin in treatment-naïve patients infected with HCV genotype 1: virology analysis of the PILLAR study”. O. Lenz; B. Fevery; L. Vijgen; J. Verbeeck ; M. Peeters; M. Beumont; M. W. Fried; G. Picchio· 1354. “The pharmacokinetic interaction between the investigational HCV NS3/4A protease inhibitor

TMC435 and escitalopram”. M. Beumont-Mauviel; A. Simion; G. De Smedt; K. Spittaels; M. Peeters; V. Sekar· 1353. “The pharmacokinetic interaction between the investigational NS3-4A HCV protease inhibitor TMC435 and methadone”.

M. Beumont-Mauviel; G. . De Smedt; M. Peeters; S. H. Akuma; V. Sekar

For more information about Medivir, please contact:Medivir (http://www.medivir.se/) Mobile: +46 708 537 292 Rein Piir, CFO & VP Investor RelationsM:Communications

Medivir@mcomgroup.com (Medivir@mcomgroup.com)+44(0)20 7920 2330Europe: Peter Laing, Amber Bielecka, Claire DickinsonUSA: Roland Tomforde +1 212 232 2356About TMC435TMC435 is a highly potent, selective, safe once-daily (QD) investigational drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infection. TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-Acting Antiviral (DAA) agents in an all oral, IFN free regimen, with or without ribavirin (RBV).TMC435 has received “Fast Track” designation by the U.S. Food and Drug Administration (“FDA”) for the treatment of chronic hepatitis C (CHC) genotype-1 infection.



For additional information from these studies, please see http://www.medivir.com/ (http://www.medivir.com/) and http://www.clinicaltrials.gov/About Hepatitis CHepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The World Health Organization estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

About MedivirMedivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.Medivir’s first product, the unique cold sore product Xerese®/Xerclear®, was launched on the US market in February 2011. Xerese®/Xerclear®, which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia.

Rights in North America, Canada and Mexico were sold to Meda AB in June 2011. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.

For more information about Medivir, please visit the Company’s website: http://www.medivir.com/ (http://www.medivir.com/)http://www.medivir.com/

T.G.I.F Hepatitis News Ticker; Hep C Drugs:Bristol-Myers, Merck and Vertex

New On The Blog

AASLD- Abstracts To Be Presented At The Nov Meeting;

AASLD-Vertex presentation of New Data; INCIVEK™and VX-222
AASLD-New Data On BMS-790052 and BMS-650032 to be presented by Bristol-Myers Squibb
AASLD-Acceptance of Four TMC435 Abstracts by Medivir
AASLD-New Data Analyses for VICTRELIS™ (boceprevir) will be Presented By Merck

Hepatitis C patients likely to falter in adherence to treatment regimen over time
Galectin-inhibiting therapeutics to treat fibrosis, liver disease and cancer
Consider Hepatitis C Infection in Some Arthritis Patients
Liver Health and Wellness

Four Ways to Beat Hepatitis Fatigue
Fatigue is a problem frequently experienced by those with chronic hepatitis. Fortunately, there are several different kinds of approaches that can help mitigate fatigue.
by Nicole Cutler, L.Ac.
As the most common symptom of chronic hepatitis, fatigue is also one of the hardest ones to address. Likely because of the complex combination of cellular and chemical processes involved in producing energy, battling fatigue is best accomplished through a variety of different approaches....

Local towns among hot spots for high rates of HIV, Hep C
NEW GLASGOW – Local groups are claiming that the incidence of AIDS, HIV and Hepatitis C is increasing rapidly in Pictou County, primarily due to a rising number of intravenous drug users in the region.

Rayann Toner, executive director of the Pictou County Centre for Sexual Health, says that a study done by Caroline Ploems for Health Canada Population and Public Health Branch shows that there are six “hot spots” in mainland Nova Scotia where injection drug use has been identified as a problem.

FYI-Pharmaceuticals


The Next Big Thing In Biotech: Hep C Drugs




Adam Feuerstein, senior columnist for TheStreet, explains why hepatitis C
drugmakers will be the biotech stocks to watch in the coming week.


ANALYSIS-Vertex takes early rounds of hep C bout with Merck

29 Sep 2011 17:48 Source: reuters // Reuters

New prescriptions for Vertex drug outpacing Merck entry

* Incivek could be one of fastest drugs to reach $1 bln

* VA contract could give boost to Merck

By Bill Berkrot
Sept 29 (Reuters) - In the bout between a pair of breakthrough hepatitis C treatments, Incivek from upstart biotech Vertex Pharmaceuticals appears to have taken the first round from pharmaceutical heavyweight Merck & Co and its Victrelis by a wide margin.

The companies next month will report sales from the first full quarter on the U.S. market for their new medicines, and weekly prescription data indicates that Merck has some serious catching up to do.

About 1,100 new patients are likely to begin Incivek treatment each week in the fourth quarter compared with about 300 new patients for Victrelis, according to Wolters Kluwer, a provider of analytical data to the healthcare industry.

It estimates U.S. Incivek sales reaching $752 million in 2011 -- a trajectory that would see the drug surpass $1 billion in its first year on the market -- making for one of the most successful drug launches in history.

Genentech's blockbuster cancer drug Avastin, which was approved in February 2004, racked up its first billion dollars in sales in about a year and a half.

In contrast, Wolters Kluwer inThought unit is forecasting $146 million in 2011 U.S. Victrelis sales.

"It's absolutely impressive," Julie Hoggatt, an analyst for inThought, said of Incivek performance out of the gate. "It does seem that Vertex, being that this was its first launch, did a very good job."

The two drugs, which promise far higher cure rates for the serious liver disease than prior standard treatments, as well as the potential for shorter treatment durations, were approved within days of each other in May.

Analysts said that Merck has made some savvy moves, including a co-promotion deal with rival Roche - the biggest seller of one of the older drugs that must be used in combination with the new medicines.

But it has so far been unable to alter the perception that Vertex has the better drug, even though the two have never been tested against each other.

In the final round of clinical trials Incivek, known chemically as telaprevir, cured between 75 percent and 80 percent of patients. Victrelis, known chemically as boceprevir, cured 66 percent. Both results easily topped the cure rate of only about 40 percent for the previous standard treatments that had to be taken for nearly a year and which often caused miserable flu-like symptoms.

SIMPLICITY, POTENCY

While many industry observers believed the Roche co-promotion would help bring the market share split much closer to 50-50, Incivek has so far been dominating.

"There was a feeling that maybe Merck could do a little bit better because they've done some unique things in the marketplace," said Deutsche Bank analyst Barbara Ryan.

"The reality is that the Vertex drug is more potent, has a more straightforward, simple dosing regimen, and for that reason they got the lion share of the market," she added.

"We still think that in some markets, like the Asian markets, that Merck will do better than its share here just because the company's presence in those markets is so strong," Ryan said.

Both drugs were recently approved in Europe, where Johnson & Johnson will sell the Vertex drug.

Hoggatt agreed that simplicity and a larger percentage of patients who qualify for shorter treatment time with Incivek were working in Vertex favor.

"One negative for boceprevir is how confusing its label is," Hoggatt said. "I think maybe seeing some hesitation from physicians because of the complexity."

Under the Victrelis regimen the two older drugs -- interferon and ribavirin -- are taken for four weeks before the Merck drug is added to the mix. There are several treatment duration variables depending on a patient response to the drugs at certain points along the way.

With Incivek, all three drugs are taken from the beginning and there are fewer pills and fewer duration variables.

"Patients are asking for telaprevir," confirmed Dr. Douglas Dieterich, a liver disease specialist and professor of medicine at Mt. Sinai School of Medicine in New York.

"It's probably going to become less telaprevir-dominated as the side effects roll in," Dieterich predicted. Incivek has been associated with serious rash in clinical trials.

But asked if patients have also been asking for the new Merck drug, Dieterich said, "No. Not at all."

Both companies have so far limited consumer marketing to campaigns aimed at raising awareness of hepatitis C, a disease that someone can have for many years without symptoms. If untreated, it can lead to cirrhosis, liver cancer and death.

"While it's still early, we are off to a good start with the launch of Victrelis and are encouraged by the positive responses we received on our product from physicians, patients and payers," Merck spokeswoman Pamela Eisele said.

Merck has won a contract for Victrelis to be the preferred treatment option by the U.S. Department of Veterans Affairs that serves thousands of patients, which should provide a boost for its drug.

But Merck may need to alter course and begin to promote its brand with consumers to get patients to start asking doctors for Victrelis if it is to close the gap.

"We thought it would be little better on the Merck side as a percent, less than 50 but certainly better than 25 percent," said Barclays Capital analyst Tony Butler.

But Butler said it was too early to declare a winner.

"In the past I've been surprised at how things have changed over time," he said. (Reporting by Bill Berkrot in New York, editing by Matthew Lewis)

Bristol-Myers Is Close To Completing A Groundbreaking Hepatitis C Treatment (BMY)
AP) — The drugmaker Bristol-Myers Squibb Co. is building a hepatitis C virus treatment franchise that could be launched by 2015 and produce as much as $2.9 billion in global sales five years later, according to a Citi analyst.

The New York company is close to starting a late-stage clinical development program for the franchise in Japan, where its opportunity is underappreciated, Citi analyst John T. Boris said in a research note late Thursday. He said it is estimated that there are as many as 2 million hepatitis C virus carriers in Japan, with 20 percent diagnosed and 30 percent treated.

Another late-stage trial was started this month and is expected to be completed in 2013

Hepatitis C is the primary cause of liver transplants in the United States and is expected to become a much larger public health problem as aging baby boomers succumb to the disease. It’s an infectious disease that can be spread by sharing needles or having sex with an infected person.

Boris said in the note he is maintaining a “buy” rating on Bristol-Myers shares, which have risen more than 17 percent in value so far this year.

The stock closed at $31.12 on Thursday after hitting a 52-week high of $31.78 earlier this month.


Combined Effects of HBV, HCV on Hepatoma Vary With Age, Gender
By Dave Levitan NEW YORK (Reuters Health)
Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is associated with substantially higher risk of hepatocellular carcinoma than single infections, but the complex interactions of the viruses vary depending on gender and age, a study from Taiwan shows. The researchers report that in general, coinfection produced weaker effects than previously reported.

"By the age of 75 years, one quarter of patients or more affected by chronic viral hepatitis will be affected by hepatocellular carcinoma," or HCC, the research team noted in an August 22nd online paper in the Journal of Clinical Oncology. Led by Dr. Yen-Tsung Huang of Harvard University, the study tracked 23,820 residents of Taiwan aged 30 to 65 years at enrollment in 1991-1992. Overall, 17.44% were seropositive for HBV surface antigen and 5.52% were seropositive for antibodies against HCV. Altogether, 477 subjects developed HCC. The cumulative lifetime incidence of HCC for was 38.35% for men with both viruses and 27.40% for women with both viruses. Men and women who were seropositive only for HBsAg had cumulative lifetime HCC rates of 27.38% and 7.99%, respectively.

These rates in men and women with only HCV were 23.73% and 16.71%, respectively. In contrast, the cumulative lifetime incidence rates for subjects with neither virus were 1.55% in men and 1.03% in women. On multivariate analysis, the hazard ratio for HCC was 19.5 for those positive for both infections. The interactive effects of the two viruses varied based on age, however. The HCC risk with dual infection was "sub-additive" before the age of 65 years, especially in men. But after age 65, the risk with dual infection was "consistently higher than that for single infection." Specifically, in older patients, the HR in men was 22.38 for dual infection vs. 8.94 and 12.34 for single infections with HBV and HCV, respectively. In women after age 65, HRs for HCC were 27.29 with dual infection, 6.58 with HBV and 15.01 with HCV. "With the increase in age, the HCC risk decreased in HBsAg-seropositive men but increased in anti-HCV-seropositive women," said study senior author Dr. Chien-Jen Chen, of the National Taiwan University in Taipei, in an email to Reuters Health.

The authors advise more intensive clinical management of patients with dual infection. "The therapy of chronic HBV/HCV infection using antivirals and/or interferon may reduce the risk of newly developed HCC," Dr. Chen said. "Frequent liver surveillance using various imaging methods (ultrasonography, CT scan, angiogram, etc.) may help early detection of small HCC, which may be treated more effectively and efficiently by surgery or embolization. The HCC case fatality may thus be lowered."
SOURCE: http://bit.ly/qydCw3

J Clin Oncol 2011. Analysis of the sustained virological response in patients with chronic hepatitis C and liver steatosis.
Piccoli LD, Mattos AA, Coral GP, Mattos AZ, Santos DE.
Abstract
CONTEXT:
Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus.
OBJECTIVE:
Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis.
METHODS:
One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology.
RESULTS:
Most patients were male (57.5%), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9%) and, in the histological evaluation, steatosis was observed in 65% of the patients (104/160). Sustained virological response in patients with steatosis occurred in 38.5%, and in 32.1% in patients without steatosis (P = 0.54). When we analyzed possible factors associated with the presence of steatosis, only body mass index and systemic arterial hypertension revealed a significant association. When the factors that influenced sustained virological response were evaluated in a logistic regression, genotype and use of pegylated interferon proved to be independent factors associated to the response.
CONCLUSION:
In the evaluated patients the presence of liver steatosis did not influence the sustained virological response of patients with chronic hepatitis C treated with interferon and ribavirin.
PMID:
21952702
[PubMed - as supplied by publisher]

HIV

From NATAP
ICAAC: ICAAC 2011: Medically Important Highlights - David H Shepp, MD, Hofstra NSLIJ Medical School Division of Infectious Diseases North Shore University Hospital - Manhasset-
Novel Treatments for HIV
Adoptive Transfer of CCR5-Modified T-cells. Combination antiretroviral therapy (ART) can suppress the growth of HIV and restore immunity to opportunistic illnesses. However, latent virus is not eliminated, requiring lifelong treatment to maintain benefit. An important thrust of current HIV research is directed to finding therapies that will allow ART to be discontinued. The apparent cure of HIV infection in a patient with leukemia who received allogeneic hematopoietic stem cell transplantation (HSCT) from a CCR5 delta 32 homozygous donor has triggered renewed interest in gene therapy for treatment of HIV

Liver Cancer

‘Micro’-chemo and Cancer Pill Combo Tested in Liver Cancer Patients
A combination of an oral drug, called sorafenib, and a method for injecting microbeads of chemotherapy directly into tumors has been proven safe for liver cancer patients and may improve outcomes for those who have these fast-growing, deadly tumors whose numbers are on the rise in the U.S.

Reporting in the Sept. 12 online version of the Journal of Clinical Oncology, Johns Hopkins investigators tested the combination in 35 patients with advanced, inoperable liver cancer. Both sorafenib and the chemotherapy drug used in this study, doxorubicin, have independently – but not in combination — been approved to treat liver cancer.

Combining the right therapies at the right time is an intense focus of study among cancer experts, and Johns Hopkins interventional radiologist Jean-Francois Geschwind, M.D., saw promise in the two therapies tested in the current study.“Both therapies have increased survival rates in advanced liver cancer, and combining them may push those survival rates further,” says Geschwind, professor of radiology, surgery and oncology at Johns Hopkins.

For the study, Geschwind employed a method called chemoembolization that uses catheters the size of a single hair to deliver microbeads filled with high concentrations of the chemotherapy drug, doxorubicin, directly to the tumor. The chemotherapy seeps out of the microbead for at least three weeks.

Sorafenib, approved for its ability to block a key pathway, depriving tumors of blood vessels, was given twice daily to patients one week before their chemoembolization procedure. “The idea is to block blood vessel formation in these cancers, which typically peaks 24 to 36 hours after chemoembolization. This may help prolong the chemotherapy’s impact.” says Geschwind.

Patients treated with the combination had no more side effects than reported for sorafenib or chemoembolization alone, according to Geschwind. Common side effects included fatigue, skin reactions in hands and feet, and body rash.


Patients in the study were admitted to the hospital overnight for their chemoembolization treatment. The patients continued oral sorafenib twice daily until their disease progressed. For the study, Geschwind says that patients received up to four chemoembolization treatments within a six-month period.Primary liver cancer incidence is rising in the U.S., says Geschwind, because of increasing rates of hepatitis C infections, which cause liver inflammation and are major risk factors for liver cancer.

Liver cancer tends to grow rapidly and without specific symptoms. Measures of a liver cancer marker called alpha-fetoprotein are elevated in only half of patients, adds Geschwind, making it difficult to find the disease early.

When the cancer is confined to the liver, doctors can transplant or remove the liver, but three-quarters of patients are not eligible for surgery. Without treatment, median survival of these inoperable patients is typically less than nine months. Chemoembolization procedures add 10 to 15 months of survival.

A phase III trial comparing chemoembolization with or without sorafenib is under way at Johns Hopkins and 100 other sites in the U.S. “We’re on the path to improving the standard of care for liver cancer,” says Geschwind.

The study was funded by Bayer Health-Care and Onyx Pharmaceuticals, manufacturer of sorafenib, and Biocompatibles, makers of the microbeads.

Researchers involved in the study include Timothy Pawlik, Diane Reyes, David Cosgrove, and Ihab Kamel, Nikhil Bhagat of Johns Hopkins.

Pawlik and Geschwind are consultants to Bayer HealthCare Pharmaceuticals, and Geschwind is a consultant to Biocompatibles. The terms of these arrangements are being managed by the Johns Hopkins University in accordance to its conflict-of-interest policies.


Liver Cancer Drug Provectus Receives Orphan Drug Designation From FDA
The U.S. Food and Drug Administration (FDA) has given orphan drug designation to Provectus Pharmaceuticals, Inc., for Rose Bengal, the active component in their new oncology medication PV-10. The drug is designed for the treatment of hepatocellular carcinoma (HCC), the most prevalent form of liver cancer. At present Provectus is designing a Phase II investigation, following the January 2011 completion of their Phase I study, which involved patient accrual and treatment of PV-10 for liver cancer in all participants...

Media

Listeriosis Deaths Climb to 13 in 'Deadliest' Outbreak
By Todd Neale, Senior Staff Writer, MedPage Today Published: September 28, 2011 The listeriosis outbreak stemming from tainted cantaloupes has sickened at least 72 individuals, killing 13 of them, according to the CDC. "This is the deadliest outbreak of a foodborne disease that we've identified in more than a decade," said CDC director Thomas Frieden, MD, MPH, on a conference call with reporters Wednesday. Overall, 18 states have been affected as of Monday, with four different strains of Listeria monocytogenes implicated. State and federal health officials are continuing to investigate other listeriosis cases across the country that might be related to the outbreak. Most of the infected individuals are older than 60 or have conditions that weaken the immune system, the CDC said in its most recent update. All but one of the patients with information on hospitalization have required admission.

The 13 confirmed deaths have occurred in New Mexico (four), Colorado and Texas (two each), and Kansas, Maryland, Missouri, Nebraska, and Oklahoma (one each). That figure is more than triple the four deaths reported last week. Early on in the investigation, the Colorado Department of Public Health and Environment identified cantaloupes grown in the Rocky Ford region of the state as the likely source of the outbreak, which is unusual because Listeria has not previously been seen in cantaloupe. Within days, the department pinpointed the exact source as whole cantaloupes grown at Jensen Farms' production fields in Granada, Colo., which was later confirmed by the FDA.

The FDA said it is working with other agencies to determine how the contamination of the facility occurred, with consideration given to all environmental factors on the farm, including possible animal intrusions, water quality, and growing practices. On Sept. 14, Jensen Farms recalled its Rocky Ford brand whole cantaloupes, reporting distribution to 17 states. In its update, the CDC said that the cantaloupes were shipped to at least 25 states, with the possibility of further distribution. Even though the cantaloupes have been recalled, the CDC said that it expects to receive reports of more cases related to the outbreak through October because individuals can develop listeriosis up to two months after coming into contact with the bacteria. The shelf life of cantaloupe is about two weeks, and all of the affected product was shipped from July 29 to Sept. 10.

The FDA said that it is collaborating with state health officials to check retail stores, wholesalers, and distributors to make sure they know about the recall and that they have taken steps to inform customers and remove affected product from shelves. The agency said that consumers should throw away any of the recalled cantaloupes from Jensen Farms and should not try to wash the bacteria off of the fruit. The CDC recommended that people at high risk for listeriosis -- including older adults, immunocompromised individuals, and pregnant women -- should not eat Rocky Ford cantaloupes from Jensen Farms, and that other individuals should not eat those cantaloupes if they want to reduce their risk of Listeria infection. The agency noted that the bacteria can grow both at room temperature and in the refrigerator.
"For the public, it's important to know that if you know the cantaloupe that you have is not [from] Jensen Farms, then it's okay to eat," Frieden said, "but if you're in doubt, then throw it out." According to the CDC, there are about 800 reported cases of Listeria infection each year in the U.S., with three or four outbreaks. Typical sources include deli meats, hot dogs, and Mexican-style soft cheeses made with unpasteurized milk, although produce -- including sprouts in 2009 and celery in 2010 -- has been implicated as well.

Frieden said over the past decade there have been about 10 outbreaks of foodborne illness in which cantaloupes were the definite vehicle for infection, seven involving Salmonella and three involving norovirus. He added that the number of multistate outbreaks of foodborne illness in general have increased substantially in recent years. "This is a reflection at least of better quality monitoring and perhaps also of the increasing complexity and centralization of the food supply," he said. "It's not that food is getting riskier, but we're getting better at identifying problems that have probably been there for a long, long time."
FDA commissioner Margaret Hamburg, MD, added that "these kinds of outbreaks are a powerful reminder that, despite the fact that we have one of the safest food supplies in the world, it does remain vulnerable to contamination, and the American people remain vulnerable to foodborne illness."

Off The Cuff

September 29, 2011, 12:01 am
Why Doctors Order So Many Tests
By PAULINE W. CHEN, M.D.
One afternoon when I was running later than usual, I recognized a familiar face among the patients waiting to see me. A voluble newspaper fanatic, the gentleman, in his 70s, was usually eager to discuss the latest headlines with me. That day, however, he was remarkably quiet. He was suffering from the flu. “I’m really feeling no good,” he rasped.

Australia: Poor Hospital Supply Lines Endanger Patients
Julie Robotham (The Sydney Morning Herald, September 29, 2011) "Hospitals operate with less than a month's supply of many essential medicines, leaving patients vulnerable if local distributors are unable to import them through fragile international supply chains. The issue was emphasized [recently when]…the sole supplier [revealed that it]…would be unable to import intravenous penicillin until December…Yvonne Allinson, the head of the Society of Hospital Pharmacists of Australia, said state and federal governments should co-operate to ensure viable supplies of essential drugs were maintained…Current purchasing policies discouraged companies from manufacturing in Australia, and incentives to encourage local research had been eroded. A spokeswoman for the Department of Health and Ageing said there were already 'well-developed processes to ensure an adequate supply of essential medicines in the Australian market,' but temporary shortages were not uncommon."

Medical marijuana as a treatment for cancer
FERNDALE -- When his cancer came back for a fifth time, Michael McShane was desperate for treatment outside of traditional medicine.
The last time squamous cell carcinoma left lumpy tumors around his mouth, doctors cut it away and reconstructed his bottom lip by turning out a portion of its inner layer.
In all, the state act defines 14 chronic or debilitating diseases, medical conditions, and side effects from treatments that qualify, including glaucoma, HIV/AIDS, hepatitis C, amyotrophic lateral sclerosis, Chrohn’s disease, agitation of Alzheimer’s disease, nail patella, Cachexia or wasting syndrome, and seizures.


video