October 17, 2013

Bristol-Myers Squibb Finds a Novel Way of Treating Hepatitis C

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by Eileen Rojas, The Motley Fool Oct 17th 2013 10:37AM
Updated Oct 17th 2013 10:38AM

For those suffering from hepatitis C, or HCV, a new therapy that combines three different drugs treated about 90% of patients, according to preliminary results from a randomized, phase 2 clinical trial supported by Bristol-Myers Squibb . That's exciting news because this therapy doesn't rely on the standard course of treatment that has been used for years -- a combination of pegylated interferon alfa and ribavirin. These two medications can produce various side effects that make treatment difficult and possibly dangerous. Positive outcomes using only interferon and ribavirin occur in only about 50% of patients with genotype 1, a difficult-to-treat form of HCV.

The new triple drug cocktail uses once-daily daclatasvir, twice-daily asunaprevir, and a twice-daily still unnamed drug referred to as BMS-791325. The drugs used in this new therapy are direct-acting agents that target the virus, unlike the standard therapy, and lead to more positive outcomes. The researchers found no adverse events that caused patients to stop treatment, and the study is being expanded to include other patient populations.

Treating viruses a profitable business for Bristol
The therapeutic area of virology, which currently includes drugs that treat hepatitis B and HIV, is a major revenue generator for Bristol-Myers. It accounted for 25% of total net worldwide sales for 2012. Net sales for the second quarter dropped 9% to $4.04 billion from $4.44 billion in the same period in 2012. GAAP diluted EPS also dropped 16% to $0.32 per share, and non-GAAP diluted EPS dropped 8% to $0.44 per share. The drop in sales is attributed to the U.S. patent expiration of cardiovascular drugs Avapro/Avalide and Plavix.

At a medical conference on liver diseases, Bristol will be presenting the first phase III study evaluating an interferon-free and ribavirin-free course of treatment for HCV. The study details the results of an oral combination of daclatasvir and asunaprevir given to Japanese patients with genotype 1b. The data, along with the presentation of 16 other abstracts, will be key in showing the company's broad pipeline of treatments for hepatitis C.

How is the competition faring?
According to Research and Markets, an international market research firm, the hepatitis C market is expected to grow by 2018 to more than three times its market size in 2012. Analysts predict that the HCV market could generate as much as $16.5 billion annually, so Bristol won't be alone in the development of new treatments for the disease.

Gilead Sciences currently has two drugs that are commercially available to treat hepatitis B (Viread and Hipsera) and five therapies in its pipeline that could become future treatments for HCV. In January 2012, the company acquired Pharmasset in an effort to speed up the development of the first all-oral HCV therapy expected to provide a new treatment option to a greater number of patients. The therapy is also expected to deliver revenue growth and diversification to the company's drug portfolio for 2014 and beyond. Gilead's total revenue grew a healthy 15% to $2.77 billion in the second quarter ended June 30, from $2.41 billion in the same period of 2012. Sales during the quarter were driven mostly by growth from its antiviral products used to treat HIV .

Another of Bristol's rivals, Abbott Laboratories has spent more than 40 years developing and improving tests that detect and monitor the various forms of hepatitis. The company's diagnostics business earned $4.3 billion in 2012, or about 20% of 2012's total net sales of $22 billion. In June of this year, Abbott announced a new fully automated test that can be used to determine the specific genotype of the HCV virus found in a patient's blood. The test, which received FDA approval, will help doctors personalize treatment by patient based on the genotype of the HCV virus, which can lead to improved outcomes. Abbott also found success with a trial that used a two- or three-drug combo, along with ribavirin, to treat HCV. Though the treatment cleared HCV in about 99% of the patients in the study, it uses the drug ritonavir, which many physicians don't want to use according to comments made by industry analyst Mark Schoenebaum to Bloomberg. Shares for Abbott closed up 4% after the results of the trial were announced.

My Foolish conclusion
It appears that the medical community is focused on moving beyond the standard therapy used to treat hepatitis C, which is intolerable for some patients and leaves many without treatment options. This creates an opportunity for pharmaceutical companies searching for new treatments that are safer and produce better patient outcomes. The latest research from Bristol-Myers and Gilead Sciences for an all-oral HCV treatment that uses newer drugs, which directly target the virus, can benefit a greater number of patients. The potential revenue streams that could result from these new therapies should pique the interest of any health care investor.

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The article Bristol-Myers Squibb Finds a Novel Way of Treating Hepatitis C originally appeared on Fool.com.


Men-only hepatitis B mutation explains higher cancer rates

Public release date: 17-Oct-2013

Contact: Jim Sliwa
American Society for Microbiology

A team of researchers has identified a novel mutation in the hepatitis B virus (HBV) in Korea that appears only in men and could help explain why HBV-infected men are roughly five times more likely than HBV-infected women to develop liver cancer. Although some women do progress to cirrhosis and liver cancer, the mutation is absent in HBV in women. The research is published ahead of print in the Journal of Clinical Microbiology.

"This is the first mutation found that can explain the gender disparity in incidence of hepatocellular carcinoma," says Bum-Joon Kim of Seoul National University, Korea, an author on the study.

In the study, the researchers randomly collected and analyzed serum samples from 292 patients with chronic HBV infection who visited one of 3 hospitals in Korea from 2003-2005. Previous studies had suggested that a gene mutation known as W4P/R was associated with higher incidence of liver cancer and cirrhosis. They developed an assay to specifically identify HBV with the W4P/R mutation. When compared to patient outcomes, the W4P/R mutation was significantly associated with severe liver disease and was found exclusively in male patients.

The investigators believe the assay they developed to discover the mutation may hold promise as a diagnostic for predicting male progression to cirrhosis and liver cancer. They caution that first larger studies are necessary to confirm their findings, as only 67 of the 292 samples came from women.

HBV infection is a global health problem, with 350 million chronic carriers of the virus, a number that is roughly equivalent to the combined populations of the US and Canada. The prevalence of infection ranges from less than half a percent in the United States to around 10 percent in Asia, to as high as 15 percent in parts of Africa. Major means of transmission include injection drug abuse, unprotected sex, and transmission via childbirth. Worldwide mortality is about 600,000 annually, according to the World Health Organization. In the US, despite the availability of a vaccine, an estimated 3,000 die annually from hepatocellular cancer or chronic liver disease caused by hepatitis B.


A copy of the manuscript can be found online at http://bit.ly/asmtip1013a. Formal publication is scheduled for the December 2013 issue of Journal of Clinical Microbiology.

The Journal of Clinical Microbiology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.


Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis

The Lancet Infectious Diseases, Early Online Publication, 17 October 2013

doi:10.1016/S1473-3099(13)70226-3 Cite or Link Using DOI

This article can be found in the following collections: Infectious Diseases (HIV/AIDS)

Copyright © 2013 Elsevier Ltd All rights reserved.

Original Text

Kenneth K Mugwanya MBChB a b, Deborah Donnell PhD c d, Prof Connie Celum MD a d e, Katherine K Thomas MS d, Patrick Ndase MBChB d, Nelly Mugo MBChB d f g, Prof Elly Katabira MBChB h, Kenneth Ngure PhD d g i, Dr Jared M Baeten MD a d e, for the Partners PrEP Study Team



Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour.


We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex—unprotected by a condom—during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour.


We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011.


Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk-taking sexual behaviour by heterosexual couples.


The Bill & Melinda Gates Foundation and the US National Institute of Mental Health.


Rates and predictors of response to anti-viral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients

Aliment Pharmacol Ther. 2013 Oct 16. doi: 10.1111/apt.12524. [Epub ahead of print]

Ioannou GN, Scott JD, Yang Y, Green PK, Beste LA.

Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Divisions of Gastroenterology, University of Washington, Seattle, WA, USA.


BACKGROUND: The effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in 'real world', clinical practice is unclear.

AIMS: To determine the rates and predictors of sustained virological response (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and ribavirin in HIV/HCV co-infected patients.

METHODS: We identified all HIV/HCV co-infected patients who received anti-viral treatment with PEG-IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n = 665).

RESULTS: Sustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1 HCV (n = 491) and 44% among patients with genotype 2 or 3 HCV (n = 116). Among genotype 1-infected patients, characteristics that were negatively associated with SVR independently included baseline HCV viral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI 0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)], baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio ≥1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR 0.41 (0.2-0.9)]; characteristics positively associated with SVR included a starting dose of ribavirin ≥1000-1200 mg/day [AOR 2.0 (1.1-3.7)] and erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor of SVR [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800 mg/day was not associated with SVR.

CONCLUSIONS: Sustained virological response rates achieved with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated with SVR.

Published 2013. This article is a US Government work and is in the public domain in the USA.

PMID: 24127691 [PubMed - as supplied by publisher]


The clinical significance of drug-drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C virus

Aliment Pharmacol Ther. 2013 Oct 16. doi: 10.1111/apt.12523. [Epub ahead of print]

Maasoumy B, Port K, Calle Serrano B, Markova AA, Sollik L, Manns MP, Cornberg M, Wedemeyer H.

Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.


BACKGROUND: Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct-acting anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P-glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.

AIM: To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.

METHODS: The first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co-medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information.

RESULTS: Out-patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co-medication in 7% and 21% of the patients respectively.

CONCLUSIONS: Many patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co-medication is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.

© 2013 John Wiley & Sons Ltd.

PMID: 24127648 [PubMed - as supplied by publisher]