Showing posts with label BMS-650032 and BMS-790052. Show all posts
Showing posts with label BMS-650032 and BMS-790052. Show all posts

Sunday, May 13, 2012

EASL Video Highlights-BMS-790052/BMS-650032 Also PSI-7977 PROTON and ELECTRON

Happy Mothers Day!

A special heartfelt Mothers day goes out to all the ladies who are burdened with the challenge of living with HCV.  Taking care of a family requires exuberant energy which at times can be difficult when living with this disease. The fatigue is unbearable and the constant worry that this disease will hinder the ability to raise our children is enormous.

May this Mothers day be filled with special moments, and lasting memories.


EASL video presentations

Today, I am once again pointing readers back to "ViralEd " and their coverage of the 2012 EASL meeting which took place last month in Barcelona (Spain). The site is great source for easy to understand information, although like any site offering continuing medical education (CME), it requires a free quick registration.

For anyone newly diagnosed with HCV understanding key data on the many HCV drugs in development is nothing less then overwhelming.

For me, the coverage of the March EASL at ViralEd is, well, enjoyable. Maybe not as enjoyable as breakfast in bed on Mothers day; that is if you get breakfast in bed. I'm still waiting to hear those three little words; Happy Mothers day. These days my kids communicate online through the social network or by text messaging. So I wait,  hoping to get tagged in a photo on Facebook, or maybe a text asking grandma to babysit. Anyhow, the entertaining video discussion format at ViralEd is less clinical, and easily digested.

Below on the blog are just a few EASL video abstracts from ViralEds "Expert Poster Review and Discussion" presentation.

Please consider viewing the complete program -"The 47th Annual EASL: Advances in Chronic Hepatitis C Management and Treatment" Unless the kids call and ask you out to lunch; I'm still waiting for my call. Not to worry its early in the day, I'd call them but for some reason they screen their calls.

Another video on the blog today was published on May 7 by , the EASL video talks a little about last months meeting, with a mention of interferon free therapy and the field of hepatology.

I wonder if I should send my eldest a text message ? I'll wait, one of my three kids will call.

*The data presented at the EASL should be considered preliminary until it has been reviewed and published in a peer-reviewed publication.

EASL 2012 Poster Program Abstract 14

Dual Oral Therapy with the NS5A Inhibitor (BMS-790052) and NS3 PI (BMS-650032) in HCV Genotype 1B-infected Null Responder or Ineligible/Intolerant to Peginterferon/Ribavirin

I watched both videos, and still no Happy Mothers Day text or any photo action on Facebook.

Poster/Presentation Listing @ ViralEd

Published on May 7, 2012 by


A video of prominent EASL members who generously dedicated precious time to the EASL film crew onsite in Barcelona to talk about key elements of the congress and the ever moving field of hepatology.

Shut the front door ! I just received a call from one-of my- three children, so off I go to enjoy Mothers day. So happy I sent that text!

Happy MOM !

Tuesday, November 8, 2011

AASLD-All-Oral Regimen of daclatasvir (BMS-790052) and (BMS-650032) 90% SVR at 12wks

All-Oral Treatment Regimen of Bristol-Myers Squibb's Investigational NS5A and NS3 Inhibitors Achieved 90% Sustained Virologic Response (SVR12) in Phase II Study Sentinel Cohort of Genotype 1b Null Responders

Results add to data suggesting that SVR can be achieved with the combination of daclatasvir (BMS-790052) and asunaprevir (BMS-650032) in HCV genotype 1b patients

PRINCETON, N.J., Nov 07, 2011 (BUSINESS WIRE) -- --Study expanded to include alfa/RBV ineligible or intolerant patients

Bristol-Myers Squibb Company today announced results from a ten patient sentinel cohort of an ongoing Phase II study in which treatment with a dual, all-oral direct-acting antiviral (DAA) regimen of the investigational NS5A replication complex inhibitor daclatasvir (BMS-790052) and the investigational NS3 protease inhibitor asunaprevir (BMS-650032) achieved undetectable viral load at 12 weeks post-treatment (SVR12) in 90% (n=9/10) of genotype 1b hepatitis C (HCV) patients who had previously not responded to peginterferon alfa and ribavirin (alfa/RBV).

Serious adverse events occurred in two patients in this study, of which one led to treatment discontinuation. The findings were presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

"Genotype 1 patients have a cure rate of about 45% when treated with interferon alfa and ribavirin. For the 55% of patients who do not achieve viral cure, further treatment has limited success, even with the addition of a protease inhibitor. There is a real unmet medical need for new treatment options that have the potential to increase response rates in null responders," said Kazuaki Chayama, MD, PhD, Professor, Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. "The results of this Phase II study of Bristol-Myers Squibb's investigational, oral direct-acting antivirals are encouraging as we study potential hepatitis C therapies for this difficult-to-treat patient population."

Based on the sentinel cohort results, the study has been expanded to include both genotype 1b patients who are null responders (n~20) and patients ineligible for alfa/RBV for medical reasons or who discontinued alfa/RBV after less than 12 weeks due to intolerance (n~20). HCV patients who are either ineligible for or intolerant to alfa/RBV represent a significant unmet medical need, as there are no effective treatments available to these patients.

Sentinel Cohort Results

Of the 10 patients enrolled in the study, nine completed 24 weeks of treatment. Rapid and persistent viral suppression was observed in all nine patients, with undetectable viral load achieved by week 8 and sustained through the end of the 24 week post-treatment follow-up period. One patient discontinued the study at Week 2. This patient had a low viral load at the time of study discontinuation (1.8 log10 IU/mL) and as reported by the investigator achieved and maintained an undetectable viral load through 24 weeks of follow-up post-discontinuation. Despite the evidence of baseline viral substitutions in some patients, there was no apparent association between those substitutions and response to treatment in this study.

Serious adverse events occurred in two patients. One patient experienced Grade 3 fever (pyrexia) and one patient developed Grade 4 elevated bilirubin levels (hyperbilirubinemia) that led to study discontinuation at week 2. As reported by the investigator, this patient achieved SVR with normalization of laboratory values upon discontinuation.

The most commonly reported on-treatment adverse events occurring in at least three patients were Grade 1 diarrhea (n=7), headache (n=4) and liver enzyme increases (n=3 ALT and AST). Of the liver enzyme increases, two patients experienced transient Grade 1 elevations and one patient had a Grade 2 elevation that began at week 16 of treatment and resolved within two weeks post-treatment.

About the Study

In this Phase II open-label clinical trial (AI447-017), a sentinel cohort of ten Japanese patients with chronic HCV genotype 1b infection with null response to prior alfa/RBV treatment (HCV RNA less-than or equal to 2 log10 IU/mL at 12 weeks of alfa/RBV therapy) were treated with daclatasvir 60 mg once daily and asunaprevir initially 600 mg twice daily and reduced to 200 mg twice daily, for 24 weeks. The primary efficacy endpoint was the proportion of patients with undetectable viral load (HCV RNA < 15 IU/mL) at 12 weeks post-treatment.

About Bristol-Myers Squibb's Commitment to Liver Disease

Bristol-Myers Squibb is advancing a portfolio of compounds that aim to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company's hepatitis C pipeline includes a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase II development for hepatitis C.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.

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 or follow us on Twitter at .

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

SOURCE: Bristol-Myers Squibb Company

Friday, September 30, 2011

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

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


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


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


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


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


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


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



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


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



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.



  • 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

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 or follow us on Twitter at

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

Source: Bristol-Myers Squibb Company

Tuesday, August 16, 2011

Hepatitis Digest;HCV abstract-BMS-790052, Liver Cancer,Vitamin D and Diabetes

HCV abstracts

Aug 2011;
Multiple ascending dose study of BMS-790052, an NS5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1

Nettles RE, Gao M, Bifano M, Chung E, Persson A, Marbury TC, Goldwater R, Demicco MP, Rodriguez-Torres M, Vutikullird A, Fuentes E, Lawitz E, Carlos Lopez-Talavera J, Grasela DM; Hepatology (Aug 2011)

The antiviral activity, resistance profile, pharmacokinetics (PK), safety and tolerability of BMS-790052, an NS5A replication complex inhibitor, were evaluated in a double-blind, placebo-controlled, sequential panel, multiple ascending dose study. Thirty patients with chronic hepatitis C virus (HCV) genotype 1 infection were randomized to receive a 14-day course of BMS-790052 (1, 10, 30, 60 or 100 mg once daily or 30 mg twice daily) or placebo in a ratio of 4:1.

RESULTS: The mean maximum decline from baseline in HCV RNA ranged from 2.8 to 4.1 log(10) IU/mL; the placebo group showed no evidence of antiviral activity. Most patients experienced viral rebound on or before day 7 of treatment with BMS-790052 monotherapy; viral rebound was associated with viral variants that had been previously implicated in resistance development in the in vitro replicon system. The PK profile was supportive of once-daily dosing with median peak plasma concentrations at 1-2 hours postdose and mean terminal half-life of 12-15 hours. Steady state was achieved following 3-4 days of daily dosing. BMS-790052 was well tolerated in all dose groups with adverse events occurring with a similar frequency in BMS-790052- and placebo-treated groups. There were no clinically relevant changes in vital signs, laboratory, or electrocardiogram parameters.

CONCLUSION: BMS-7590052 is the first NS5A replication complex inhibitor with multiple dose proof-of-concept in clinic. At doses of 1-100 mg daily, BMS-790052 was well-tolerated, had a PK profile supportive of once-daily dosing, and produced a rapid and substantial decrease in HCV-RNA levels in patients chronically infected with HCV genotype 1. (HEPATOLOGY 2011.)

Genotypic and phenotypic analysis of variants resistant to HCV NS5A replication complex inhibitor BMS-790052: In Vitro and In Vivo correlations
Fridell RA, Wang C, Sun JH, O' Boyle DR, Nower P, Valera L, Qiu D, Roberts S, Huang X, Kienzle B, Bifano M, Nettles RE, Gao M; Hepatology (Aug 2011)

The NS5A replication complex inhibitor BMS-790052 inhibits hepatitis C virus (HCV) replication with picomolar potency in preclinical assays. This potency translated in vivo to a substantial antiviral effect in a single-ascending dose study and a 14-day multiple-ascending dose (MAD) monotherapy study. However, HCV RNA remained detectable in genotype 1a-infected patients at the end of the MAD study. In contrast, viral breakthrough was observed less often in patients infected with genotype 1b and, in several patients, HCV RNA declined and remained below the level of quantitation (<25 IU/mL) through the duration of treatment. Here we report results of the genotypic and phenotypic analyses of resistant variants in 24 genotype 1-infected patients who received BMS-790052 (1, 10, 30, 60 and 100 mg, once daily or 30 mg, twice daily) in the 14-day MAD study. Sequence analysis was performed on viral cDNA isolated from serum specimens collected at baseline and days 1 (4, 8, and 12 hours), 2, 4, 7, and 14 postdosing. Analyses of the sequence variants (i) established a correlation between resistant variants emerging in vivo with BMS-790052 treatment and those observed in the in vitro replicon system (major substitutions at residues 28, 30, 31 and 93 for genotype 1a, and residues 31 and 93 for genotype 1b); (ii) determined the prevalence of variants at baseline and the emergence of resistance at different times during dosing; and (iii) revealed the resistance profile and replicative ability (fitness) of the variants.

CONCLUSION: Although resistance emerged during monotherapy with BMS-790052, the substantial anti-HCV effect of this compound makes it an excellent candidate for effective combination therapy. (HEPATOLOGY 2011.)

BMS-790052 Plus BMS-650032

From CCO;EASL 2011
Expert Analysis
BMS-790052 Plus BMS-650032 With or Without Peginterferon alfa-2a/Ribavirin in Previous Null Responders With Genotype 1 HCV Infection
AJ is a genotype 1 HCV–infected patient who experienced a null response with previous peginterferon/ribavirin therapy. He is hesitant to start treatment with telaprevir or boceprevir once approved, as he does not feel that that the chances of SVR are worth the adverse effects he experienced with peginterferon previously. He is curious to know whether any data thus far have shown SVR among patients treated with an interferon-free regimen.

How can you advise this patient?

To View Capsule Summary Free Registration Is Required

Stefan Zeuzem, MD: In another study investigating the efficacy of combining DAA agents, Lok and colleagues[35] combined the HCV NS5A replication complex inhibitor, BMS-790052, with the HCV NS3 protease inhibitor, BMS-650032, with or without peginterferon alfa-2a/ribavirin in patients infected with genotype 1 HCV who experienced previous null response to peginterferon/ribavirin therapy (Capsule Summary). In this open-label phase IIa trial, 21 patients were randomized to dual therapy with BMS-790052 60 mg once daily plus BMS-650032 600 mg twice daily or to quadruple therapy with the same doses of BMS-790052 and BMS-650032 plus peginterferon alfa-2a/ribavirin. Treatment was for 24 weeks, and patients with virologic breakthrough were eligible to add peginterferon/ribavirin therapy for up to 48 additional weeks. The primary endpoint was SVR12.

Although the patient numbers are small, all 10 patients receiving quadruple therapy for 24 weeks achieved SVR12. By contrast, only 4 out of 11 patients receiving dual therapy achieved SVR12. Patients were stratified by genotype 1 HCV subtype and no more than 2 patients with genotype 1b HCV were allowed in each treatment arm. The investigators did not state why there was a limit to the number of patients with genotype 1b HCV; however, in the dual therapy arm, both patients with genotype 1b infection achieved SVR12. The high SVR12 rate among patients with genotype 1b infection receiving dual therapy would be more convincing if there would have been more than 2 patients infected with this HCV subtype enrolled.

Graham R. Foster, FRCP, PhD: Virologic response differences according to genotype 1 subtype have been demonstrated in clinical studies with protease inhibitors as discussed previously, but there are few data as yet on the impact of HCV subtype on clinical response to NS5A inhibitors.
In an ascending dose study of another NS5A inhibitor, AZD7295, HCV RNA levels exhibited dose-dependent reductions among patients with genotype 1b HCV, but not among patients with genotype 1a or 3 infection.[36]

Stefan Zeuzem, MD: An analysis of in vitro culture systems demonstrated a lower EC50 of BMS-790052 for genotype 1b vs 1a; however, the values for both subtypes are in the subnanomolar range and the dose administered in this trial should have been effective for both subtypes.[37] Therefore, it remains an open question and further studies are needed.
In the current BMS-790052/BMS-650032 combination study, 6 out of 11 patients treated with dual therapy did not achieve undetectable HCV RNA at the end of therapy (Week 24) and experienced virologic breakthrough at various time points. A seventh patient experienced viral relapse, resulting in 4 patients (36%) with SVR12, including both patients with genotype 1b infection and 2 patients with genotype 1a infection. On the other hand, patients receiving quadruple therapy achieved an impressive 100% rate of undetectable HCV RNA at the end of treatment, and this outcome was maintained at 12 weeks after stopping therapy as mentioned previously.
At posttreatment Week 24, 1 patient in the quadruple therapy arm appeared to have detectable but not quantifiable HCV RNA; however, a retest 35 days later showed that the patient once again had undetectable HCV RNA. Therefore, the SVR rate at posttreatment Week 24 in this arm was formally 90%. The fact that all patients who received just 24 weeks of quadruple therapy were cured is a very impressive result considering that all of the patients enrolled in this trial experienced a previous null response, defined as a < 2 log10 IU/mL decline in HCV RNA after 12 weeks of peginterferon/ribavirin therapy.

Graham R. Foster, FRCP, PhD: This study represents an exciting step forward, suggesting that combining 2 potent drugs with peginterferon and ribavirin may be highly effective in some of the most challenging patients. More data are needed to clarify whether peginterferon/ribavirin are a necessary component for this patient population or whether interferon-free regimens may be possible.

Stefan Zeuzem, MD: This study and previous studies of alisporivir monotherapy in treatment-naive patients are the only public data we have suggesting that SVR can be possible with interferon-sparing regimens. Three patients with genotype 3 HCV and 1 with genotype 1 HCV have been cured and were cured with alisporivir monotherapy according to data presented to date.[38] The fact that 4 previous null responders achieved SVR with BMS-790052/BMS-650032 dual therapy provides some support for the contention that indeed interferon-sparing regimens are possible.

Paul Y. Kwo, MD: This study provides a glimpse into the future of treatment for null responders. A particularly important issue regarding these findings is that some of the most difficult to treat patients, including some null responders, are people who cannot tolerate peginterferon and ribavirin; these data lend great hope to that substantial population.
Stefan Zeuzem, MD: As yet there are no data regarding predictors of SVR to these regimens for previous null responders. The only predictor that may be assumed at this time is HCV subtype 1b; however, even this assumption is too preliminary. More data from larger trials will be needed before we can determine which patients might be appropriate candidates for an interferon-sparing regimen or whether quadruple therapy would be recommended.

Graham R. Foster, FRCP, PhD: This study provides an exciting start, but it is important to emphasize that these data are very preliminary and involve a very small number of patients. Patients may see these data and expect that 2-drug regimens will be available in the near future; however, even if these data can be confirmed in larger studies, it will be quite some time before such regimens are available. Therefore, patients with cirrhosis certainly cannot afford to wait until that time. Nonetheless, even clinicians with a strong belief in the value of interferon are beginning to consider that interferon may have a more limited future.

March 31, 2011 Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained Virologic Response in Phase II Dose-Ranging Study of Treatment-Naive Hepatitis C Patients

EASL 2011-
HCV Cured With out Peginterferon/ribavirin with 2 oral HCV drugs BMS790052+BMS650032: Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: "HCV infection can be cured without interferon & ribavirin: 2 orals BMS790052+BMS650032" - (04/02/11)

Liver Cancer

Two Liver Cancer Discoveries May Impact Hepatitis Patients
Researchers in different countries make two liver cancer discoveries, progress that could have a positive impact on people with advanced chronic Hepatitis B or Hepatitis C.
by Nicole Cutler, L.Ac.
Millions of Americans are currently living with chronic Hepatitis B or Hepatitis C, viral illnesses that can cause significant damage to the liver. Unfortunately, chronic viral hepatitis is the most prominent risk factor for developing hepatocellular carcinoma (HCC), a primary liver cancer. Extraordinarily hard to treat, hepatocellular carcinoma is one of the most perilous types of cancer possible. However, two newly released studies that examined liver cancer on molecular levels could lead to improved treatments - a potential relief to many people with advanced Hepatitis B or Hepatitis C.

Deferoxamine Shows Promise for Liver Cancer in People with Advanced Disease
Deferoxamine, a cancer drug that has an anti-proliferative effect on tumor cells, led to improvement of hepatocellular carcinoma (HCC) in 2 out of 10 patients with moderate-to-severe liver disease, according to a letter in the August 11, 2011, New England Journal of Medicine.

Hepatocellular Carcinoma After Diagnosis of Hepatitis B or C Infection
New Non-Invasive Technology Shows Promise in Shrinking Liver Tumors
Peginterferon Maintenance Therapy in Patients with Advanced Hepatitis C to Prevent Hepatocellular Carcinoma: The Plot Thickens
Watch; RF ablation alternative to surgery in early liver cancer
Metabolic syndrome increases risk of both major types of primary liver cancer


Generic Drug Makers May Soon Pay for Overseas Plant Inspections - ABC News
By (@kimcarollo)
Aug. 16, 2011

VIDEO: One of the world's largest generic drug makers is calling on its fellow manufacturers to help foot the bill for the U.S. Food and Drug Administration to conduct inspections of overseas pharmaceutical plants.

Up to 40 percent of the drugs Americans use are imported, and around 80 percent of the active ingredients in those drugs are made in foreign facilities.
The FDA only inspected 11 percent of the more than 3,700 foreign manufacturing sites in 2009, according to data from the U.S.Government Accountability Office. All manufacturing facilities in the United States, however, are subject to FDA inspection every two years.

Healthy You

The mysteries of belly fat
Health professionals are concerned about belly fat because it can trigger: heart disease, stroke, high blood pressure, diabetes, fatty liver, liver cancer, stress, depression and Alzheimer's. Scientists believe that it is the fat below the surface, called visceral fat, that really does the damage by producing hormones and chemicals that can cause heart disease and more. Also, evidence shows that deep-seated fat near an important vein that leads to the liver can transport fatty acids to the organ.

The result: high blood lipid readings. How do you know when the size of your stomach is putting you in peril? A general guideline is that woman with a waist of more than 35 inches, and a man over 40 inches, could be at more risk. As we age, most people struggle with weight. This is because metabolism slows down causing lean muscle mass to be lost, therefore burning fewer calories.

But there's more: Menopause Typically, women face the menopause phase of their lives sometime between the ages of 45 and 55. It is a profound change where a women's body produces less estrogen and progesterone. One of the results of this can be weight gain, which tends to be around the middle rather than the hips. This shift can begin even before, in the period called perimenopause....Continue reading....

Nearly Everyone Needs a Routine Vitamin D Supplement
By: MITCHEL L. ZOLER, Internal Medicine News Digital Network
NEW YORK – The vast majority of children and adults should receive a routine, daily vitamin D supplement, and this recommendation applies from age 1 year all the way up to age 70 years, Dr. Henry W. Lim said at the meeting.
The only exception is a select group of people at high risk for vitamin D inadequacy who warrant initial testing to be sure they don’t need an even higher starting dosage of the vitamin, said Dr. Lim, professor and chairman of dermatology at Henry Ford Hospital in Detroit.

Only people at risk for vitamin D inadequacy, such as breastfed infants or people with limited sun exposure, should be tested for serum vitamin D level, according to Dr. Henry W. Lim.
Dr. Lim based his recommendations on the revised dietary reference intakes for vitamin D issued by the Institute of Medicine last November, which set a recommended dietary allowance (RDA) of 600 IU/day for ages 1-70 years.
"In my opinion, testing [of serum vitamin D level] should only be done for people at high risk for vitamin D inadequacy," he said. In the group to consider for testing are breastfed infants, older adults with reduced skin synthesis of vitamin D, or people with limited sun exposure, dark skin, fat malabsorption (because vitamin D is fat soluble), or obesity.
"For the average individual [not in a high-risk group] my suggestion is to take 600 IU per day starting at age 1," Dr. Lim said in an interview. At that level, the supplement is relatively innocuous, inexpensive, and addresses the widespread vitamin D inadequacy. He did not rule out routine vitamin D supplements for children younger than 1 year, but noted that the RDA is lower.

Testing a person’s vitamin D level costs about $100, using ICD-9 code 268.9 for unspecified vitamin D deficiency. Doing that for everyone would incur a "tremendous" cost, he said. He also echoed the recent position taken by the American Academy of Dermatology that most vitamin D should come from diet and supplements, and not from sun exposure. "It is inappropriate to recommend intentional exposure to natural or artificial UV [light] for achieving an adequate vitamin D level," he said.

People at high risk for a low vitamin D level need testing to check whether their level falls as low as 10 ng/mL or even 5 ng/mL. With this degree of deficiency, the person might need a single 10,000-IU or even 20,000-IU dose to raise their level quickly. Daily supplements should not exceed 1,000-3,000 IU in children aged 8 years or younger and should not exceed 4,000 IU daily for those aged 9-70 years, Dr. Lim said.

Two types of vitamin D are available in supplement form, D2 and D3 (ergocalciferol and cholecalciferol, respectively). The vitamin D3 form is preferable because it is more effective at raising serum levels, it attaches better to vitamin D–binding protein, and it has a longer shelf life, Dr. Lim said.

He also reviewed the evidence documenting benefit from adequate vitamin D levels. He concurred with the IOM that the best evidence by far to support maintaining a minimum serum vitamin D level involves the vitamin’s effect on skeletal health. For other outcomes, the evidence is "inconsistent, inconclusive, and insufficient to inform nutritional requirements," Dr. Lim said.
Dr. Lim said that he has been a consultant to La Roche-Posay L’Oreal, Clinuvel, and Procter & Gamble and has been an investigator for Clinuvel.

World's Healthiest Foods
Food of the Week: Cucumbers
Sun, 14 Aug 2011 18:39:26


Exercising with Diabetes Complications
Mon, 15 Aug 2011 10:22:49
If you have had diabetes for a long time and have developed complications, you may have questions about whether you should be engaging in physical activity—and if so, what kind of physical activity is best for your condition.

According to Jacqueline Shahar, MEd, RCEP, CDE, a clinical exercise physiologist and manager of Exercise Services in the Joslin Clinic at Joslin Diabetes Center, patients with diabetes complications should definitely continue to find appropriate opportunties for physical activity. In the Joslin’s Easy Start program many patients have significant diabetes complications and are able to exercise regularly and safely as part of their diabetes self-management plan.
There is always some type of exercise people with complications can do. Not remaining activity can lead to developing additional complications and loss of functional capacity (the ability to do the activities of daily living).

Here are some of the more common diabetes complications and recommendations for exercise for each;

Peripheral Neuropathy
Peripheral neuropathy is nerve damage in the extremities, causing tingling, pain or loss of sensation in your toes, feet and fingers. Peripheral neuropathy increases the risk of loss of balance—and subsequently the increased risk of falling. In addition, the pain and burning can make it difficult to walk.
Exercise prescription:
Incorporate balance exercises and avoid weight-bearing activities such as walking or jogging. Good choices are the stationary bike and swimming.

Charcot Foot
Charcot Foot is a specific type of peripheral neuropathy in which there is destruction of the nerves on the bottom of the foot. The foot eventually becomes deformed and loses sensation. It is important to stay off your feet as much as possible.
Exercise prescription:
Use a stationary or arm bike, or do chair exercises using free weights in a seated position.

Proliferative Retinopathy
Proliferative retinopathy is advanced diabetic eye disease in which new, fragile cells develop on the optic disc. These new cells are prone to leakage or hemorrhage into the eye resulting in loss of vision. You may also be at risk for retinal detachment.
Any exercises that increase blood pressure should be avoided. You need to avoid lifting heavy objects and any vigorous exercise. In addition, do not perform any exercise that requires forward bending such as yoga or the valsalva maneuver [The Valsalva maneuver or Valsalva manoeuvre is performed by moderately forceful attempted exhalation against a closed airway, usually done by closing one's mouth and pinching one's nose shut. Variations of the maneuver can be used either in medical examination as a test of cardiac function and autonomic nervous control of the heart, or to "clear" the ears and sinuses (that is, to equalize pressure between them) when ambient pressure changes, as in diving, hyperbaric oxygen therapy, or aviation].
Exercise prescription:
Stick to non weight bearing exercise such as moderate intensity biking or walking in the pool. Or try slow, steady hiking, ballroom dancing or elliptical machines at low to moderate intensity.

Nephropathy is damaged to the kidneys, which eventually leads to complete kidney shutdown and the need for dialysis. With nephropathy, exercise capacity is decreased because of the buildup of waste products in the body.
Exercise prescription:
Light to moderate exercise is encouraged.

Other Issues to Consider When Exercising with Complications
Autonomic (central) neuropathyAutonomic (central) neuropathy can cause significant cardiac changes.The usual heart rate guidelines for exercise don’t apply. Instead use the talk test to determine if you are exercising at an acceptable level. In addition, if you have autonomic neuropathy, you may no longer experience the symptoms of low blood glucose and need to check your blood glucose more frequently.
Foot ulcer or foot deformity—non weight-bearing exercises are preferred as well as keeping the feet clean dry. You should avoid swimming,
The Talk Test
Light intensity exercise—you can sing or whistle while exercising
Moderate intensity exercise—you can talk while exercising
High intensity exercise—you can’t talk
3 Things to Remember When You Exercise with Diabetes!
It is important to check with your health care provider before starting any exercise program.
Always check your blood glucose before and after any exercise routine.
Making an appointment with an exercise physiologist can be very helpful if you have any complications of diabetes.


Hot Weather Takes Toll on Medication
Mon, 15 Aug 2011 21:49:30
The recent heat wave may have taken a toll on your medication. That’s what reporter Walecia Konrad learned after her son’s allergy medication stopped working after being exposed to high temperatures on a family vacation at the lake.
No drug should be exposed to temperatures higher than 86 degrees. Some days the bathroom at our vacation house and certainly the trunk of the car were well above that mark….

Saturday, April 2, 2011

Bristol-Myers Interferon-Free Combo And 4-Drug Combo Impressive "BMS-650032/BMS-790052" Plus SOC

Quadruple therapy shows 100 percent SVR for HCV patients previously unresponsive to treatment

Is this treatment approach the next HCV therapy frontier?

Berlin, Germany, Saturday 02 April 2011: Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple therapy in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after treatment (SVR12).1

In the quadruple therapy study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).

The current standard of care (SoC) for HCV therapy is PegIFN-alpha plus RBV – a dual therapy. The addition of DAAs (currently in phase-III clinical trials) marks the next step in treatment evolution – a triple therapy. However, the new data presented today suggests that quadruple therapy could be the next generation of treatment for chronic HCV patients.

Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple therapy is possibly the future of HCV treatment; this study goes a way to confirming that. While it's expected that the first DAAs and triple therapy will be approved for use later this year, quadruple therapy appears to have a more profound effect on virological response, with less of a resistance problem."

The study may also provide new hope for a growing number of HCV patients who cannot be effectively treated for chronic hepatitis with current treatments.

The Phase-IIa trial looked at a cohort of 21 HCV genotype 1 null responders (patients who have failed to respond to previous treatment), of whom 19 had an unfavourable IL28B genotype, which predisposes HCV patients to treatment failure.

Only about 30% of null responders to PegIFN-alpha/RBV treatment achieve sustained virological response (SVR) when retreated with PegIFN-alpha/RBV plus telaprevir, demonstrating a high unmet medical need.1

Notes to Editors

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year

Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology

Journal of Hepatology published monthly

Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2011

The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

1. Lok A et al. Quadruple therapy with BMS-790052, BMS-650032 and peg-IFNRBV for 24 weeks results in 100% SVR12 in HCV genotype 1 null responders. Abstract presented at The International Liver CongressTM 2011.

Bristol-Myers Interferon-Free Combo Cured Hepatitis Patients

By Naomi Kresge - Apr 2, 2011 12:48 PM ET
Bristol-Myers Squibb Co. (BMY)’s cocktail of two experimental drugs cured four hepatitis C patients in the first success for a therapy that excludes often-toxic existing drugs.

The combination had a higher rate of success when paired with the current standard treatment in the 21-person trial, curing nine of 10 patients, researchers said today at the Berlin meeting of the European Association for the Study of the Liver. The study points to the next generation of drugs for the evasive virus, said Mark Thursz, a professor of hepatology at Imperial College London and vice-secretary of EASL.

Bristol-Myers, based in New York, is among about a dozen companies trying to make better drug combinations that either include interferon, a decades-old shot that causes flu-like symptoms and only works in half of patients, or that replace interferon entirely. At stake is leadership in a market that Jefferies International Ltd. estimates may total $15 billion a year by 2019.

“This is perhaps one of the most exciting developments this year,” Thursz said in an interview. “For some patients who are not going to tolerate interferon, this is the light at the end of the tunnel.”

Bristol-Myers plans to begin the last trials required for regulatory approval this year, Douglas Manion, the drugmaker’s head of neuroscience and virology research, said in an interview.


Today’s trial studied the Bristol-Myers drugs, BMS-790052 and BMS-650032, in patients for whom existing therapies hadn’t been successful, “the toughest-to-treat population,” Manion said.

Ten patients got the two drugs together with interferon and generic ribavirin. All showed no sign of the virus 12 weeks after the treatment was over. One patient had signs of virus at 24 weeks and was again virus-free in another follow-up test 35 days later.

Of 11 patients who took the Bristol-Myers combination alone, five had cleared the virus from their bodies at the end of treatment. Four remained virus-free after 24 weeks.

Patients may start treatment earlier if they aren’t faced with the toxic side effects of traditional hepatitis C drugs, said Howard Liang, a Boston-based analyst for Leerink Swann & Co., in an interview.

“If you have an interferon-free regimen, the market expands fairly dramatically,” Liang said.

Side Effects

Side effects of the existing interferon regimen are often severe enough to force patients to take time off work, said Charles Gore, president of the Geneva-based patient advocacy group World Hepatitis Alliance.

Roche Holding AG (ROG) of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey markets a form called PegIntron.

Merck, Vertex Pharmaceuticals Inc. (VRTX) and Johnson & Johnson are expected to bring the first new hepatitis C drugs in a decade to the market this year. About 90 percent of patients who responded quickly to treatment with Johnson & Johnson (JNJ) and Vertex’s telaprevir were cured, Cambridge, Massachusetts-based Vertex said in two studies last year. Three-quarters of all patients were cured. Patients who responded quickly to Merck’s boceprevir showed similarly high cure rates in studies last year, with about two-thirds of all patients being cured.

The Vertex and Merck trials included people who hadn’t yet been treated, an easier-to-cure group than those in today’s smaller study. By comparison, about 30 percent of those who hadn’t responded to previous treatment were cured after trying telaprevir plus standard therapy, researchers said.

Seeking Partners

Merck is seeking partnerships to gain its own hepatitis C drug combinations, Patrick Bergstedt, general manager of the infectious diseases franchise, said in an interview.

“We’re behind the others,” Bergstedt said. “We need to partner to fill the gap.”

Bristol-Myers expects an “element of consolidation” as companies use acquisitions, partnerships and research and development collaborations to gain their own hepatitis C drug combinations, Manion said. After signing a development deal with Princeton, New Jersey-based Pharmasset Inc. (VRUS) in January, Bristol- Myers is “talking to pretty much every company out there,” he said.

“This is like trying to redesign a car as you’re rolling down the road at 100 miles per hour, because the data are coming so fast,” he said. “What an exciting time.”

To contact the reporter on this story: Naomi Kresge in Frankfurt at
To contact the editor responsible for this story: Phil Serafino at

Bristol-Myers Presents HCV Data

Recently, Bristol-Myers Squibb Company (NYSE: BMY - News) presented encouraging data from a phase II study (n=48) which evaluated its candidate BMS-790052 as a combination therapy for treating patients suffering from the hepatitis C virus (HCV). Bristol-Myers presented data from the mid-stage study at the 46th annual meeting of the European Association for the Study of the Liver in Germany.

The double-blind study evaluated BMS-790052 at three doses (3 mg, 10 mg or 60 mg) in treatment-naïve patients infected with genotype 1 chronic HCV. Results from the study revealed that the rate of SVR12 (sustained virologic response – absence of detectable HCV at 12 weeks post treatment ) achieved by patients treated with a combination of BMS-790052, PEG-interferon alfa and ribavirin (the standard of care) was higher across all evaluated doses than those receiving placebo in combination with PEG-interferon alfa and ribavirin. The patients were divided equally into four groups.

Patients in the 10 mg arm achieved the highest rate (92%) of SVR12. 83% and 42% patients achieved SVR12 in the 60 mg and 3 mg arms of BMS-790052 respectively. Adverse events and serious adverse events were found to be consistent with those in the PEG-Interferon alfa and ribavirin arm across all 3 doses of BMS-790052.

We believe that if BMS-790052 is developed and commercialized successfully then it would not only boost Bristol-Myers’ portfolio but would provide a wider choice to HCV patients in a lucrative market that has a huge unmet need.

More On The Study; EASL; BMS-790052 Plus PEG-Interferon Alfa/Riba Achieved Up to 92% SVR-Naïve Geno1 HCV Patients