March 8, 2011

Telaprevir, Boceprevir Boost SVR in Hep C

Perspective: We are on the verge of triple-drug regimens that will improve response rates for genotype 1 hepatitis C to where rates for genotype 2/3 have been, while shortening the duration of therapy to 24 weeks for many patients, which can lower both cost and side effects. However, therapy will be more complex and will require closer monitoring to manage side effects and monitor for and prevent resistance.

DR. ROBERT S. BROWN JR. is the Frank Cardile Professor of Medicine and Surgery and Chief of the Center for Liver Disease and Transplantation at Columbia University College of Physicians and Surgeons, New York.

BY DIANA MAHONEY
Elsevier Global Medical News
 
BOSTON – The forthcoming availability of the protease inhibitors telaprevir and boceprevir for the treatment of chronic hepatitis C is likely to vastly improve virologic response rates and cut treatment times, but experts warn that such advancements need to be balanced against the huge potential for misuse of the agents and the need to manage side effects and monitor for antiviral resistance.

When used in combination with standard therapy consisting of pegylated interferon plus ribavirin, each of these investigational drugs improved sustained virologic response (SVR) rates and reduced treatment duration, compared with standard therapy alone, in four pivotal, phase III trials reported at the annual meeting of the American Association for the Study of Liver Diseases.

Previous Nonresponders Benefit From Boceprevir

Response-guided, fixed-duration therapy with boceprevir was safe and effective in a cohort of HCV genotype 1 patients who were enrolled in the RESPOND-2 study and who failed standard therapy, said lead investigator Dr. Bruce R. Bacon of St. Louis University. The 403 patients included those in whom prior standard therapy resulted in either a partial response (HCV RNA less than 2 logs at 12 weeks but still positive) or a relapse, he said.

All patients underwent a 4- week lead-in phase of standard therapy followed by random assignment to continue standard therapy alone or in conjunction with 800 mg of boceprevir taken three times daily.

The treatment duration was 36 weeks for patients in the boceprevir arm with undetectable HCV RNA at study weeks 8 and 12, whereas those patients in whom HCV RNA was detectable at study week 8, but undetectable at week 12, stopped boceprevir at week 36 but continued standard therapy for an additional 12 weeks (total of 48 weeks). Controls were treated for 48 weeks.

The SVR rates at 24 weeks after treatment conclusion were significantly higher in the boceprevir groups, compared with the control group. In the responseguided and fixed-duration boceprevir groups, the SVR rates were 59% and 66%, respectively, compared with 21% in the control patients, Dr. Bacon said.

In the two boceprevir study arms, “previous historical relapsers and partial responders fared better than the patients receiving standard of care,” he noted.

Although the rates of anemia were significantly higher in the boceprevir arms, “the rate of treatment discontinuation related to side effects was similar across all three arms,” Dr. Bacon reported, possibly because the use of erythropoietin was allowed to treat anemia, he said.

The findings of this study answer an important question about response-guided therapy “by confirming that many patients can be treated successfully with a treatment duration that is reduced by 3 months relative to the current standard of care treatment,” Dr. Bacon said.

Boceprevir with a standard therapy lead-in strategy was also evaluated in the SPRINT-2 study involving HCV genotype 1 treatment-naive patients, according to Dr. Fred Poordad of Cedars-Sinai Medical Center in Los Angeles. The trial included 1,097 patients who underwent a similar 4-week standard therapy lead-in as defined above, followed by the addition of placebo for 44 more weeks or by the addition of boceprevir, either for 24 more weeks for patients with undetectable HCV RNA at week 8 or for 24 more weeks plus 20 additional weeks of standard therapy for patients with detectable HCV RNA at week 8, but not at week 24, Dr. Poordad explained. Patients with detectable HCV RNA at week 24 were discontinued for futility, he said.

“In both the response-guided and fixed-treatment arms, boceprevir increased viral cure rates significantly, by approximately 70%,” Dr. Poordad stated. The SVR rate was 63% in the 28-week response-guided group, 66% in the 48-week fixed-duration group, and 38% in the 48-week control group, he said.

In a cohort analysis of treatment response for the study’s 159 black patients, the relative improvement in SVR rates remained significant in the boceprevir arms, although the differences were not as robust, Dr. Poordad said. In this subgroup, the respective SVR rates in the response- guided therapy, fixed-duration therapy, and control groups were 42%, 53%, and 23%.

The rationale for using a lead-in strategy “is to help physicians identify patient responsiveness to interferon before adding boceprevir,” Dr. Poordad said. This can provide an early indication of the likelihood of treatment success. The advantage of subsequent response-guided therapy, he noted, is that it enables physicians to be flexible in managing their patients’ therapy “by adapting treatment duration to individual patient response.”

Telaprevir Boosts Viral Cure Rates

In the ADVANCE trial, a three-arm, double-blind, placebo-controlled study, investigators compared two telaprevir-based regimens with standard therapy in 1,088 treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection, according to lead investigator Dr. Ira M. Jacobson, AGAF, of New York Weill Cornell Medical Center in New York City.

Patients in treatment arms 1 and 2 received 750 mg of telaprevir plus standard therapy for 8 and 12 weeks, respectively, whereas patients in the control group received standard therapy alone, which consisted of 180 mcg/week of pegylated interferon alfa-2a and 1,000-1,200 mg/day of ribavirin.

Patients who had extended, rapid virologic response (RVR) – defined as undetectable HCV RNA viral load at treatment weeks 4 and 12 – were treated with standard therapy for an additional 16 and 12 weeks in the 8- and 12-week telaprevir arms, respectively, for a total of 24 weeks, Dr. Jacobson explained. Patients in whom HCV RNA was detectable at either week 4 or 12 received an additional 40 and 36 weeks of therapy, respectively, for a total of 48 weeks. The control group underwent standard therapy for 48 weeks.

Compared with 44% of patients in the control group who achieved SVR 24 weeks after the last treatment, significantly more patients in both telaprevir arms – 69% of the 8-week group and 75% of the 12-week group – met that end point, Dr. Jacobson reported. The extended RVR rates in the 8- and 12-week groups were 57% and 58%, respectively, compared with 8% in the control arm.

Significantly improved SVRs were also observed in difficult-to-treat subgroups. “Among black patients, the [SVR] rates were 58% and 62% in the 8- and 12-week treatment arms, and 25% in the control arm, and in cirrhotic patients the respective rates were 53%, 62%, and 33%,” he said. Rates of treatment discontinuation due to adverse events, such as rash and anemia, were 8% and 7% in the 8-and 12-week telaprevir groups and 4% in the control group, “which is an improvement, compared with the previously reported profile,” he said.

The phase III, open-label ILLUMINATE trial was designed to determine whether extending the telaprevir and standard therapy regimen from 24 to 48 weeks would be beneficial in treatment-naive, genotype 1 HCV patients who achieved extended RVR. In all, 540 patients were initially treated with the 12-week telaprevir regimen described above. Of the 352 patients who achieved RVR, 322 remained on treatment and were randomized to either a 24-week or 48-week treatment arm.

“The [SVR] rates associated with the 24-week and the 48-week arms were statistically similar, at 92% and 87.5%, respectively,” reported Dr. Kenneth E. Sherman of the University of Cincinnati. Analyses of the data based on race and extent of liver damage showed that 88% of black patients who had extended RVR achieved SVR in both the 24- and 48- week treatment arms, and 82% and 88% of patients with advanced fibrosis/cirrhosis achieved SVR in the 24-week and 48-week arms, respectively, he said.

There were more adverse event–related treatment discontinuations in the longertreatment group (12.5% vs. 0.6%), suggesting a benefit to the shorter duration, Dr. Sherman said. The high viral cure rate observed in the study – the overall SVR rate was 72% in an intent-to-treat analysis – “[supports] the role of response-guided therapy with telaprevir-based regimens” in treatment-naive patients,” he said.

All the sources disclosed relationships with numerous pharmaceutical companies. Among them, Dr. Jacobson and Dr. Sherman disclosed relationships with Vertex Pharmaceuticals, which manufactures telaprevir. Dr. Jacobson also has a relationship with Tibotec, which also is involved with the development of telaprevir. Dr. Poordad and Dr. Bacon also disclosed relationships with Merck, which manufactures boceprevir.

Source
J Hepatol. 2011 Feb 24. [Epub ahead of print]

Gane EJ, Rouzier R, Stedman C, Wiercinska-Drapalo A, Horban A, Chang L, Zhang Y, Sampeur P, Nájera I, Smith P, Shulman NS, Tran JQ.

Auckland Clinical Studies, New Zealand.

Abstract

BACKGROUND AND AIMS: Danoprevir (RG7227; ITMN-191) is a potent inhibitor of the HCV NS3/4A serine protease. The aims of this double-blind, placebo-controlled, multiple-ascending dose phase Ib study were to evaluate safety, tolerability, antiviral activity, resistance and pharmacokinetics of once- and twice-daily danoprevir in the presence of low-dose ritonavir (danoprevir/r) and in combination with peginterferon alfa-2a (40KD)/ribavirin in treatment-naive HCV genotype 1 patients.

METHODS: Thirty eligible patients were enrolled into 3 cohorts and treated with danoprevir/r or placebo/r all in combination with peginterferon alfa-2a (40KD)/ribavirin for 15 days. Cohort 1 received danoprevir/r at 100/100mg twice daily; Cohort 2 200/100mg once daily; and Cohort 3 200/100mg twice daily.

RESULTS: The median reductions in HCV RNA from baseline after 14 days of treatment (day 15) were -5.1, -4.8 and -4.6 log(10) IU/mL in Cohorts 1, 2 and 3, respectively, and -2.7 log(10) in placebo/r and peginterferon alfa-2a (40KD)/ribavirin recipients. Viral breakthrough was not observed in any patient. On day 15 HCV RNA was undetectable (<15 IU/mL) in 6/9 (67%), 4/8 (50%) and 8/8 (100%) patients in Cohorts 1, 2 and 3 respectively. When co-administered with low dose ritonavir, danoprevir concentrations reached steady state between 6 to 10 days of dosing. Danoprevir exposures increased more than dose proportionally between 100/100 mg and 200/100 mg. Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin was well-tolerated with no safety-related discontinuations.

CONCLUSIONS: Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin provides profound and robust reductions in serum HCV RNA, at substantially lower systemic exposures compared to those observed with higher doses of danoprevir in the absence of ritonavir. These results support further studies of danoprevir/r.

Copyright © 2011. Published by Elsevier B.V.

Source
J Hepatol. 2011 Feb 24. [Epub ahead of print]

Deltenre P, Corouge M, Canva V, Castel H, Wartel F, Dharancy S, Louvet A, Lazrek M, Moreno C, Henrion J, Mathurin P.

Service d'Hépato-Gastroentérologie, Hôpital Huriez, CHRU Lille, Lille, France; Service d'Hépato-Gastroentérologie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium.

Abstract

INTRODUCTION: Undetectable HCV RNA at 12 weeks is the stopping rule recommended in HCV patients in whom previous treatment has failed. Whether earlier virological criteria may be useful for deciding treatment discontinuation remains subjects to debate.

AIM: To identify, in HCV-1 non-responders and relapsers to IFN or Peg-IFN and ribavirin, the earliest and most accurate predictor of failure to respond to a new treatment combining Peg-IFN and ribavirin.

METHODS: Prediction of SVR was assessed using the area under the ROC (AUROC) curve of reduction in viral load at different time points.

RESULTS: This study included 151 patients (32% with extensive fibrosis or cirrhosis). A SVR was reached in 34% (21% in non-responders and 59% in relapsers). In non-responders, 1 month was the most accurate time point for predicting SVR (AUROC: 0.787±0.075, p=0.0001). Thirty-seven percent of non-responders did not have a 1-log drop in viral load at 1 month. All these patients had detectable HCV RNA at 3 months (p<0.0001) and only 4% attained a SVR (p=0.004). The same high negative predictive value for SVR was found in sensitivity analysis restricted to non-responders to Peg-IFN and ribavirin. In contrast, in relapsers, undetectable HCV RNA at 3 months was the earliest criterion with high negative predictive value (92%, p<0.0001).

CONCLUSION: All HCV-1 non-responders who did not have a 1-log drop in viral load at 1 month remained HCV-RNA-detectable at 3 months, and only 4% attained a SVR. This new criterion can be used early on as a first stopping rule.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21354445 [PubMed - as supplied by publisher]

Source
J Hepatol. 2011 Feb 24. [Epub ahead of print]

Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, Ferrari C, Missale G, Zeuzem S, Pawlotsky JM, Schalm S, Hellstrand K, Neumann AU, Lagging M; the DITTO-HCV study group.

Service of Infectious Diseases, Department of Medicine, University Hospital and University of Lausanne, Switzerland.

Abstract

BACKGROUND: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.

METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.

RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted P<0.001) and lower rapid (15% vs. 38%, adjusted P=0.007) and sustained viral response rates (48% versus 66%, adjusted P<0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (P=0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted P=0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted P=0.04), but not with second phase decline.

CONCLUSION: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21354446 [PubMed - as supplied by publisher]

Source

Pharmasset Hep C Data Wows Investors

By Adam Feuerstein 03/08/11 - 11:46 AM EST

PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS_) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.

Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.

These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.

Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.

The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.

EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.

While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.

None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.

Source

Subset of HIV/HCV Co-infected at Risk for Hepatic Steatosis

By: MARY ANN MOON, Internal Medicine News Digital Network

03/01/11

In patients co-infected with HIV and hepatitis C virus, alcohol use and a high body mass index are associated with progression of hepatic steatosis, whereas exposure to certain antiretrovirals and a high baseline CD4 count appear to be protective against steatosis, Dr. Tinsay A. Woreta and her colleagues reported in the March issue of Gastroenterology.

In their study of 222 patients who were co-infected with HIV and HCV, more than 90% showed no progression of steatosis during nearly 3 years of follow-up.

The findings indicate that efforts to diagnose and prevent hepatic steatosis "should be focused on persons with a high body mass index and excessive alcohol intake," said Dr. Woreta of Johns Hopkins University, Baltimore, and her associates (Gastroenterology 2011 March [doi:10.1053/j.gastro.2010.11.052]).

Hepatitis C virus is not uncommon in patients with HIV infection, and hepatic steatosis affects 30%-70% of those with both infections. The steatosis is associated with hepatic fibrosis and is thought to contribute to the more rapid progression of liver disease in co-infected patients than in those who don’t have concomitant HIV.

"The natural history of hepatic steatosis is incompletely understood" because most studies have been cross-sectional rather than longitudinal," wrote Dr. Woreta and her colleagues. They performed their longitudinal study to prospectively examine the natural history of steatosis, using data from HIV/HCV–co-infected patients who underwent serial liver biopsies while attending an urban HIV clinic.

There were 345 pairs of serial biopsies available for analysis. The study subjects had a median age of 44 years; 66% were men and 87% were black. Nearly half were overweight or obese. Almost all (94%) had HCV genotype 1.

Most patients (194, or 87%) had no or only trivial hepatic steatosis at baseline, and it did not progress during follow-up in 165 (74%) of them. The other 29 patients who had no or only trivial hepatic steatosis at baseline progressed to significant steatosis during follow-up.

In all, 28 patients had significant hepatic steatosis at baseline, and the steatosis actually regressed in 21 (75%) of them. The other seven patients who had significant hepatic steatosis at baseline maintained that steatosis.

Persistence or progression of steatosis was strongly associated with a history of alcohol abuse. Although few patients reported current alcohol abuse, the medical records showed chronic alcoholism or abuse in approximately half. Many study subjects were probably underreporting their current exposure, particularly because they were aware that they were participating in a study of liver outcomes. "Clinicians evaluating fatty liver disease in HIV-infected patients should remain cognizant about the likelihood of underreporting of alcohol consumption," the investigators noted.

Obesity also was strongly associated with persistent or progressive steatosis, which was not unexpected. Although HIV infection was, until a short time ago, "a progressively fatal disease characterized by severe wasting, the advent of HAART [highly active antiretroviral therapy] has transformed HIV into a chronic disease with an increase in the prevalence of obesity."

"These data underscore the importance of measures to prevent and treat obesity in HIV/HCV–co-infected patients, [given] the development or worsening of hepatic steatosis in these patients," the researchers said.

Longer exposure to antiretroviral therapy appeared to be protective against persistent or progressive steatosis. One possible mechanism for this finding is that HIV infection may promote steatosis by facilitating HCV replication in hepatocytes, so reducing the HIV load would ease steatosis.

"Another possibility is that HIV acts synergistically with HCV to disrupt lipid metabolism. Thus, direct inhibition of HIV viral replication could decrease steatosis, particularly if the antiretroviral agent [has] minimal impact on mitochondrial replication and function," Dr. Woreta and her colleagues said.

They emphasized that stavudine, which has been designated as a "nonpreferred" antiretroviral agent because it was thought to contribute to steatosis, was used by only 6% of patients in this study, so the authors were unable to assess its effects.

A higher CD4 cell count at baseline also appeared to be protective against steatosis. The investigators did not offer any possible explanations for this effect. No association was found between steatosis progression and patient age, sex, race, diabetes status, HCV genotype, fibrosis status, or HCV therapy, they noted.

This study was supported by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the National Center for Complementary and Alternative Medicine, the Agency for Healthcare Policy and Research, and the clinical research unit at the Johns Hopkins Medical Institutions. The investigators reported that they had no financial conflicts of interest.

Source
Public release date: 2-Mar-2011

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

Genetic variants determine severity of HCV-related graft disease and antiviral treatment response

German researchers have found a significant association of IL28B genotypes to interferon-based antiviral treatment outcome, and to graft inflammation caused by hepatitis C virus (HCV). The study determined that the presence of G-allele serves as a marker for severe HCV-induced graft inflammation, as well as a predictor for unsuccessful treatment. Study findings—the largest to report on the role IL28B variants in a transplant cohort with recurrent HCV—are published in the March issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases.

The IL28B gene encodes interferons (IFNs), which are proteins made by lymphocytes to motivate the immune system in the presence of pathogens. IFN-α proteins are produced by leukocytes and are prevalent in the presence of a viral infection such as HCV. Researchers determined the prevalence of IL28B genotypes (GG, GT, TT) in 183 liver transplant patients, analyzing 605 protocol liver biopsies performed six months to ten or more years after transplantation.

The authors determined that the presence of G-allele was a marker for more severe graft inflammation and was observed to have a strong association to antiviral treatment failure in 103 of 159 patients. T-allele was more frequent among patients with lower inflammation grades, concluding a definite association between IL28B G-allele and HCV-induced graft inflammation, and the G-allele as a predictor of unsuccessful antiviral treatment. The team also found that IL28B genotypes did not seem to affect median fibrosis.

"Successful liver transplantation creates a unique population of quasi-normal individuals relying on a harmonic interaction of two different genetic backgrounds," said Dennis Eurich, MD, from the Department of General, Visceral and Transplant Surgery at Charité, Campus Virchow in Berlin and lead author of the current study. "IL28B polymorphisms may help to identify patients at risk for developing more severe graft hepatitis. These genetic variants might help to individually predict potential response to antiviral therapy, enabling medical professionals to appropriately adapt treatment."

A related editorial also published in Liver Transplantation this month acknowledges the association between IL28B polymorphisms and HCV-induced graft inflammation, and the prediction of treatment outcomes. Geoffrey McCaughan from the Centenary Institute in Australia said, "The exact mechanisms of how this association results in higher sustained virologic response rates remain unclear, however the data has invigorated research into both prediction of treatment outcomes and the mechanisms of control of HCV replication and clearance."

Infection with HCV is the primary cause of cirrhosis of the liver and liver cancer worldwide. Up to 30% of liver transplants will develop graft cirrhosis within five years after liver transplantation due to recurrent HCV-infection. HCV-induced graft fibrosis is the main determinant of morbidity and mortality of liver transplant patients.

###

These studies are published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.

Full citation: "Relationship between IL-28b Gene Polymorphism and Histological Severity of HCV-Induced Graft Inflammation and Response to Antiviral Therapy after Liver Transplantation." Dennis Eurich, Sabine Boas-Knoop, Martin Ruehl, M. Schulz, Esperanza Carrillo, Thomas Berg, Ruth Neuhaus, Peter Neuhaus, Ulf Neumann, and Marcus Bahra. Liver Transplantation; Published Online: December 6, 2011 (DOI: 10.1002/lt.22235) Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22235/abstract.

Editorial: "Liver Transplantation in Hepatitis C; Will Understanding the IL28B Polymorphisms Improve Outcomes?" Geoffrey McCaughan, Nicholas Shackel, and David Bowen. Liver Transplantation; Published Online: January 14, 2011 (DOI: 10.1002/lt.22252); Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22252/abstract.

About the Journal

Liver Transplantation is published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society . Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AALSD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty.

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

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Previous studies have already established that individuals with HIV are more likely to suffer from osteoporosis. Now, the latest research has found a corollary to this effect. According to a new investigation, HIV-positive patients who have hepatitis C have even higher rates of osteoporosis than those without the liver disease.

The findings, which were published in the Journal of Hepatology, pointed to the need for increased vigilance for bone loss among people co-infected with HIV and hepatitis C.

The National Institutes of Health estimates that osteoporosis is already four times more likely among people with HIV than among those without the disease.

HIV and hepatitis C are both incurable diseases, though each may be brought under control with medical treatments and prescription medications.

Approximately 20,000 new cases of hepatitis C - a chronic liver disorder that causes inflammation scarring and even failure of the organ - occur every year in the U.S., according to the Centers for Disease Control and Prevention.

By contrast, new HIV infections are nearly three times as prevalent. The agency reports that more than 56,000 new cases of HIV are contracted annually.

In the new study, scientists analyzed the bone mineral density of around 180 patients who had tested positive for both HIV and hepatitis C. Around 28 percent of the participants, most of whom were middle-aged African-Americans, tested positive for osteoporosis.

Bone density scans found that these patients were most likely to have low bone mass in the spine, followed by the hip and leg.

In contrast to these results, the study's authors said that previously gathered data indicate that people infected solely with HIV have between a 15 and 20 percent chance of having osteoporosis.

The team concluded that while further research into the interactions between HIV, hepatitis C and bone tissue is merited, physicians should strongly consider testing all patients with HIV or hepatitis for decreased bone density.

More than 10 million Americans have osteoporosis and another 34 million are at risk for it, according to the National Osteoporosis Foundation.
 
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CAMBRIDGE, Mass., March 7, 2011 /PRNewswire/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that two abstracts have been accepted for presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL, March 30- April 3, 2011 in Berlin, Germany). Full abstracts can now be viewed at the EASL website at http://www.easl.eu/.

The accepted abstracts are as follows:

• Standring, et al, "Idenix NS5A HCV Replication Inhibitors with Low Picomolar, Pan-Genotypic in vitro Antiviral Activity" will be presented in a poster session beginning on Friday, April 1.

• Standring, et al, "No Resistance to IDX184 Was Detected in 3-day and 14-day Clinical Studies of IDX184 in Genotype 1-Infected HCV Subjects" will be presented in a poster session on Saturday, April 2.

About Idenix

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus. For further information about Idenix, please refer to http://www.idenix.com/.

Forward-looking Statements

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of our drug candidates, the likelihood and success of any future clinical trials involving our drug candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the company's dependence on its collaborations with Novartis Pharma AG and GlaxoSmithKline/ViiV Healthcare; changes in the company's business plan or objectives; the ability of the company to attract and retain qualified personnel; competition in general; and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the company's annual report on Form 10-K for the year ended December 31, 2010, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the company files with the SEC.

All forward-looking statements reflect the company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the company's estimates change.

Idenix Pharmaceuticals Contact:
Kelly Barry (617) 995-9033 (media)
Eric Hoffman (617) 224-4485 (investors)

SOURCE Idenix Pharmaceuticals, Inc.
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http://www.idenix.com/

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March 08, 2011 08:00 AM Eastern Time

2011 Meeting of the European Association for the Study of the Liver

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced that data from its Phase 1 clinical trial of IMO-2125, its novel immune modulator for the treatment of chronic hepatitis C virus (HCV) infection, in treatment-naïve genotype 1 HCV patients will be presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held March 30 – April 3, 2011 in Berlin, Germany. The presentation entitled "IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naïve genotype 1 HCV patients: a Phase 1 trial,” D. Guyader, et al., will be made in a poster session entitled Viral Hepatitis C: Clinical (new compounds, resistance) on Saturday, April 2, 2011. The full abstract (#1209) can now be accessed through the EASL website http://www.easl.eu/.

About IMO-2125

IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.

About Idera Pharmaceuticals, Inc.

Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables it to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.

Idera Forward Looking Statements

This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements; whether results obtained in preclinical and clinical studies such as the studies referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Quarterly Report on Form 10-Q for the three months ended September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.

Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com

Source

Pharmasset to Challenge Vertex Hepatitis C Treatment, BMO Says

By Naomi Kresge - Mar 8, 2011 9:57 AM ET

Pharmasset Inc. (VRUS)’s experimental hepatitis C therapies may pose a challenge to treatments from Vertex Pharmaceuticals Inc. (VRTX), based on trial results to be released in late March, BMO Capital Markets Corp. analysts said.
 
Two drugs from Pharmasset showed “impressive” figures as stand-alone medications or combination therapies, while results from a two-drug combination from Vertex weren’t good enough to justify more patient studies, the analysts, led by Jason Zhang in Montreal, wrote in a research report to investors yesterday, citing abstracts of the trials.

The Vertex trial combined its drug telaprevir, due for U.S. regulatory review on May 23, with experimental drug VX-222, Zhang wrote. The Pharmasset trials combined two experimental therapies, PSI-7977 and PSI-938, with standard therapies or with each other. Zhang lowered his recommendation on Vertex’s stock from “outperform” to “market perform,” saying that investors already expect telaprevir to be approved.

“The hepatitis C treatment landscape subsequent to the initial phase of telaprevir dominance is tilting away from Vertex to companies such as Pharmasset that have potent combinations,” Zhang wrote.

Vertex fell as much as 5.1 percent to $47.07 and was down 5 percent in Nasdaq trading as of 9:53 a.m. in New York. That pared the stock’s gain this year to 35 percent, valuing the Cambridge, Massachusetts-based company at $9.64 billion. Princeton, New Jersey-based Pharmasset jumped as much as 7.3 percent to $66.48 and was up 4 percent.

Telaprevir may generate $1.9 billion in revenue in 2012, according to BMO’s estimates.

The trials were summarized in abstracts released yesterday by the European Association for the Study of the Liver. Though published online, the data are under a press embargo until the conference, which starts on March 30 in Berlin.

To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Source

Gilead Drug Combination Cut Hepatitis Virus in Study, RBC Says

By Kristen Hallam - Mar 8, 2011 7:27 AM ET

Gilead Sciences Inc. (GILD)’s four-drug combination eliminated hepatitis C virus in patients in an early-stage study, RBC Capital Markets LLC analysts said.

The findings support an ongoing mid-stage study of the combination, the analysts, led by Michael Yee in San Francisco, wrote yesterday in a note to investors, citing an abstract of the trial. The analysts said they expect data next year from a mid-stage study by the Foster City, California-based company.

The early-stage study examined a combination of Gilead’s GS-9256 and GS-9190 with two older drugs that are the standard of care, ribavirin and Peg-interferon, according to the note.

The data will be presented at the annual meeting of the European Association for the Study of the Liver starting March 30 in Berlin.

To contact the reporter on this story: Kristen Hallam in London at khallam@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Source
March 07, 2011 01:51 PM Eastern Time

Data Demonstrate Focused Execution of the Company’s Hepatitis C R&D Strategy

PRINCETON, N.J.--(BUSINESS WIRE)--New Phase II data on multiple Bristol-Myers Squibb Company (NYSE: BMY) investigational hepatitis C compounds will be presented at The International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, from March 30 to April 2. The data presentations, including three late-breaker presentations, demonstrate the rigorous execution of the company’s strategy to develop potential improvements in the care of patients living with Hepatitis C infection by using multiple approaches to target the virus.

Bristol-Myers Squibb will present three late-breaker presentations, including a poster presentation of the first public disclosure of 12-week data on sustained virologic response (SVR) with the NS5A inhibitor BMS-790052 in combination with PEG-Interferon alpha-2a and ribavirin (IFNα/RBV) in treatment-naïve HCV patients. Additionally, SVR 12-week data on quadruple therapy with BMS-790052, the NS3 inhibitor BMS-650032 and IFNα/RBV in null responders will be presented in the late-breaker oral presentation session on Saturday, April 2. Complete early virology response (cEVR) data from the Phase IIb EMERGE study of PEG-Interferon lambda and ribavirin versus IFNα/RBV in treatment-naïve patients will also be presented in a late-breaker oral presentation.

“Bristol-Myers Squibb is focused on advancing the science to address significant unmet medical needs for patients with liver disease,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data at the International Liver Congress reflect the breadth of our hepatitis C pipeline and the multiple approaches we are taking to bring forward potential new options for a disease that today impacts approximately 170 million people worldwide.”

BMS-790052 and BMS-650032 were discovered by Bristol-Myers Squibb Research and Development. PEG-Interferon lambda was discovered by ZymoGenetics, Inc., a wholly-owned subsidiary of Bristol-Myers Squibb.

The Bristol-Myers Squibb data presentations at ILC are as follows: 

March 31

First report of SVR12 for a NS5A Replication complex inhibitor, BMS-790052 in combination with PEG-IFNα-2A and RBV: Phase 2a trial in treatment-naïve HCV-Genotype 1 subjects (Poster Board # 1373)

S. Pol
Hôpital Cochin
Paris, France

--------------------

April 1

In Vitro DAA combination studies to address HCV clinical findings (Poster Board # 803)

J.A. Lemm
Bristol-Myers Squibb

--------------------

April 1

BMS-766, A Novel HCV NS5a inhibitor with enhanced resistance coverage (Poster Board # 787)

M. Gao
Bristol-Myers Squibb

--------------------

April 1,
4:45 –5:00 p.m.

Characterization of Virologic Escape in HCV Genotype 1 Null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052 (Oral Session)

F. McPhee
Bristol-Myers Squibb

--------------------

April 2

BMS-650032, an NS3 inhibitor, in combination with Peginterferon Alfa-2a and Ribavirin in treatment-naïve subjects with genotype-1 chronic hepatitis C infection (Poster Board # 1195)

J. Bronowicki
Hôpital Adultes De Brabois
Vandoeuvre Les Nancy, France

--------------------

April 2

No early virologic breakthrough observed with the HCV NS3 protease inhibitor BMS-650032 in multiple dose monotherapy studies and Phase 2a combination studies with PEG-INF alpha/RBV (Poster Board # 1223)

F. McPhee
Bristol-Myers Squibb

--------------------

April 2

The burden of hepatitis C in Europe: a propensity analysis of patient outcomes (Poster Board # 1192)

M. daCosta
DiBonaventura
Kantar Health
New York, New York

--------------------

April 2

Estimating the incidence and prevalence of hepatitis C infection in England using back projection methods (Poster Board # 1166)

P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK

--------------------

April 2

Cost benefit analysis of response guided therapy: dynamic disease Markov modeling for patients with chronic hepatitis (HCV) by fibrosis stages (Poster Board # 1167)

P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK
--------------------

April 2,
3:30 – 5:30 p.m.

Pegylated Interferon-Lambda (PEGIFN-λ) shows superior viral response with improved safety and tolerability versus PEGIFNα-2A in HCV patients (G1/2/3/4): EMERGE Phase IIb through week 12 (Late-Breakers Oral Session)

S. Zeuzem
Klinikum der Johann-Wolfgang Goethe-Universität, Frankfurt/Main, Germany

--------------------

April 2,
3:30 – 5:30 p.m.

Quadruple therapy with BMS-790052, BMS-650032 and PEG-IFN/RBV for 24 weeks results in 100% SVR12 in HCV Genotype 1 null responders (Late-Breakers Oral Session)

A. Lok
University of Michigan
Ann Arbor, Michigan

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.

Contacts
Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com

Source
March 07, 2011 10:44 AM Eastern Time

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new data analyses from Phase III studies of VICTRELIS™ (boceprevir), its investigational oral hepatitis C protease inhibitor, will be presented at The International Liver CongressTM / 46th European Association for the Study of the Liver (EASL) annual meeting. The meeting will be held from March 30 – April 3 in Berlin. In total, more than 20 abstracts highlighting Merck medicines and investigational therapies for chronic hepatitis C virus (HCV) infection will be presented, including 3 oral presentations and 17 posters for VICTRELIS.

Presented for the first time will be final results from a Phase III study of VICTRELIS administered in combination with Pegasys® (peginterferon alfa-2a) and ribavirin in adult patients with chronic HCV genotype 1 infection who were non-responders or relapsers to previous pegylated interferon and ribavirin therapy.

The EASL presentations will also include new analyses of the pivotal Phase III data for VICTRELIS administered in combination with PEGINTRON® (peginterferon alfa-2b) and ribavirin from the HCV SPRINT-2 and HCV RESPOND-2 studies:

• Response-guided therapy with VICTRELIS in combination with current standard therapy among patients with chronic HCV genotype 1, including special populations such as those with advanced fibrosis / cirrhosis;

• Overall safety profile of VICTRELIS administered in combination with current standard therapy for chronic HCV; and

• Potential predictive factors for chronic HCV treatment success, including response following 4 weeks of lead-in therapy and IL28B polymorphism.

The abstracts were published today and can be accessed on the EASL website. For program information, please visit http://www2.kenes.com/liver-congress/Pages/Home.aspx.

VICTRELIS (Boceprevir) Oral Presentations

Parallel Session: HCV Therapy, Thursday, March 31, 17:00 – 19:00, Hall 1

Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus (HCV) Genotype-1 with Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies; S. Bruno et al. 17:15 – 17:30 CET

Boceprevir Resistance-Associated Variants (RAVS) are Observed More Frequently in HCV (Gt1)-Infected Patients with Poor Response to Peginterferon Alfa-2b/Ribavirin; S. Zeuzem et al. 17:45 – 18:00 CET

IL28B Polymorphism Predicts Virologic Response in Patients with Hepatitis C Genotype 1 Treated with Boceprevir (BOC) Combination Therapy. F. Poordad et al. 18:30 – 18:45 CET

VICTRELIS (Boceprevir) Key Poster Presentations

High Sustained Virologic Response (SVR) Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir Plus Peginterferon Alfa-2A/Ribavirin. S. Flamm et al. Late-Breaker Abstract 1366. Thursday, March 31.

Response-Guided Therapy with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin Reduces Duration in Naive and Peginterferon Alfa-2b/Ribavirin Previous-Treatment-Failure Patients with HCV Genotype 1. M.P. Manns et al. Abstract 448. Thursday, March 31.

Overall Safety Profile of Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. M.P. Manns et al. Abstract 449. Thursday, March 31.

Four-Week Therapy with Peginterferon Alfa-2b/Ribavirin Effectively Predicts Sustained Virologic Response in Treatment-Naïve and Previous-Treatment-Failure Patients with HCV-1 Treated with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. J.M. Viering et al. Abstract 481. Thursday, March 31.

Utility of Historical Data Compared to Lead-In Response in Predicting Sustained Virologic Response in Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir+Peginterferon Alfa-2b/Ribavirin (P/R). R. Esteban et al. Abstract 418. Thursday, March 31.

About the HCV RESPOND-2 and HCV SPRINT-2 Studies

The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:

• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated

• patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and

• 48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).

In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).

As previously reported, the U.S. Food and Drug Administration has granted priority review status to the New Drug Application (NDA) for VICTRELIS and the Marketing Authorization Application (MAA) for VICTRELIS has been accepted for accelerated assessment by the European Medicines Agency. Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with peginterferon alpha and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous 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. 2011 marks the 10-year anniversary of the introduction of PEGINTRON and ribavirin in combination therapy, a current standard therapy for chronic HCV worldwide. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis care.

About PEGINTRON

PEGINTRON is indicated for use in combination with ribavirin for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease.

The following points should be considered when initiating therapy with PEGINTRON in combination with ribavirin: (1) These indications are based on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.

PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.

The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with ribavirin is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, ribavirin. Combination therapy provides substantially better response rates than monotherapy.

Selected Safety Information on PEGINTRON

WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS

Alpha interferons, including PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGINTRON therapy.

Use with Ribavirin: Ribavirin may cause birth defects and death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.

Contraindications

PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/ribavirin combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL per min.

Pregnancy

Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.

Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:

• Hemolytic anemia with ribavirin

• Neuropsychiatric events

• History of significant or unstable cardiac disease

• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication

• New or worsening ophthalmologic disorders

• Ischemic and hemorrhagic cerebrovascular events

• Severe decreases in neutrophil or platelet counts

• History of autoimmune disorders

• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis

• Pulmonary infiltrates or pulmonary function impairment

• Child-Pugh score greater than 6 (Class B and C)

• Increased creatinine levels in patients with renal insufficiency

• Serious, acute hypersensitivity reactions and cutaneous eruptions

• Dental/periodontal disorders reported with combination therapy

• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)

• Weight loss and growth inhibition reported with combination therapy in pediatric patients.

Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.

Adverse Events

Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and ribavirin were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and ribavirin were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.

The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/ribavirin combination therapy weight-based (12 percent) or flat-dose (17 percent). In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In a study with PEGINTRON/ribavirin (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based ribavirin group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/ribavirin combination therapy and three occurred during the follow-up period but had been on PEGINTRON/ribavirin combination therapy.

Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.

Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/ribavirin are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.

The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/ribavirin therapies. Weight-based PEGINTRON/ribavirin dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/ribavirin (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.

Subjects receiving PEGINTRON/ribavirin as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naïve patients receiving this regimen.

In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/ribavirin are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.

Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.

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 http://www.merck.com/.

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 (http://www.sec.gov/).

Please see attached Prescribing Information, Medication Guide, and Instructions for Use including Boxed Warning for PEGINTRON. The Prescribing Information, Medication Guide, and Instructions for Use are also available at http://www.spfiles.com/pipeg-intron.pdf, http://www.spfiles.com/mgpeg-intron.pdf and http://www.spfiles.com/ifupeg-intron.pdf.

Endnote

1 SVR, the protocol specified primary efficacy endpoint, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.

VICTRELIS™ and PEGINTRON® are trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA

Pegasys® is a trademark of its respective owner and is not a trademark of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Source
Mar 07, 2011 08:00 ET

TUSTIN, CA--(Marketwire - March 7, 2011) - Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that data from the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV has been accepted for presentation at the 46th annual meeting of the European Association for the Study of the Liver (EASL) taking place in Berlin, Germany from March 30 to April 3, 2011.

The abstract can be accessed through the EASL website http://www2.kenes.com/liver-congress/Pages/Home.aspx. In accordance with the EASL embargo policy, the accepted abstract titled "Escalating Repeat Dose Study of Bavituximab in Patients Co-infected with Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus" (poster 1239) will be presented in a poster session on Saturday, April 2, 2011.

About Peregrine Pharmaceuticals

Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com/), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com/.

Peregrine Contact:
Amy Figueroa
Peregrine Pharmaceuticals
(800) 987-8256
info@peregrineinc.com

Source
- Complete results from pivotal Phase 3 REALIZE study of telaprevir in people who had not achieved a viral cure (SVR) with currently available medicines -

- First presentation of data from ongoing Phase 2 study evaluating response-guided, 12- and 24-week regimens of telaprevir and VX-222 combined with pegylated-interferon and ribavirin -

- Analyses of the relationship between IL28B genotype status on viral cure rates from two Phase 3 studies -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that 15 abstracts on the company's medicines in development for hepatitis C, including its protease inhibitor, telaprevir, and polymerase inhibitor, VX-222, were accepted for presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, March 30 to April 3, 2011.

Highlights of data presentations include:

• Complete results from the pivotal Phase 3 REALIZE study will be presented for the first time. Topline results from this study, which evaluated telaprevir in combination with pegylated-interferon and ribavirin in people who had not achieved a viral cure (SVR) with currently available medicines, were announced in September 2010.

• The first data from an ongoing Phase 2 study evaluating 12- and 24-week response-guided regimens of telaprevir and VX-222 in combination with pegylated-interferon and ribavirin will be presented during a late-breaker session (Abstract #1363).

• Retrospective analyses of the relationship between IL28B genotype status and rates of viral cure with telaprevir-based combination therapy from the pivotal Phase 3 studies of REALIZE and ADVANCE will also be presented.

The titles of the abstracts related to Vertex's medicines in development for hepatitis C are included below and the complete abstracts are now available through the EASL website at http://www.easl.eu/.

"This is an exciting time for the treatment of hepatitis C and for Vertex," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "At EASL, we will present, for the first time, complete results from the Phase 3 REALIZE study and early findings of a new study evaluating both of our oral medicines in development for hepatitis C, telaprevir and VX-222 in combination with available medicines."

The regulatory applications for the approval of telaprevir have been granted Priority Review by the U.S. Food and Drug Administration (FDA) and Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people chronically infected with genotype 1 hepatitis C virus (HCV). The applications include data from three registrational studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the telaprevir clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.

Oral Presentations

• "REALIZE Trial Final Results: Telaprevir-based Regimen in Genotype 1 Hepatitis C Virus infection in Patients with Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin"; March 31, 2011, 4:15 - 4:30 p.m. CET.

• "Subanalyses of the telaprevir lead-in arm in the REALIZE study: response at week 4 is not a substitute for prior null response categorization"; March 31, 2011, 5:00 - 5:15 p.m. CET.

• "Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials (ADVANCE, ILLUMINATE, REALIZE)"; March 31, 2011, 5:30 - 5:45 p.m. CET.

• "Similar SVR Rates in IL28B CC, CT or TT Prior Relapsers, Partial- or Null-Responders Patients Treated with Telaprevir/Peginterferon/ Ribavirin: Retrospective Analysis of the REALIZE Study"; March 31, 2011, 6:45 - 7:00 p.m. CET.

Poster Presentations

• Late Breaker #1363: "VX-222 with TVR Alone or in Combination with Peginterferon ALFA-2A and Ribavirin in Treatment-Naïve Patients With Chronic Hepatitis C: ZENITH Study Interim Results"; March 31 — April 2, 2011.

• Late Breaker #1369: "Telaprevir Substantially Improved SVR Rates Across All IL28B Genotypes in ADVANCE Trial"; March 31 — April 2, 2011.

• #451: "Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Analyses of Pre-Defined Subpopulations in the Phase 3 ADVANCE Trial"; March 31, 2011, 1:30 — 2:30 p.m. CET.

• #415: "Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin Increased Sustained Virologic Response Rates in Treatment-Naïve Patients Regardless of Race or Ethnicity"; March 31, 2011, 1:30 — 2:30 p.m. CET.

• #477: "Anemia Had no Effect on Efficacy Outcomes in Treatment-Naïve Patients who Received Telaprevir-Based Regimen in the ADVANCE and ILLUMINATE Phase 3 Studies"; March 31, 2011, 1:30 — 2:30 p.m. CET.

• #400: "Modeling, Clinical and Virology Data From Phase 2 and 3 Studies Support 12-week Telaprevir Duration In Combination with 24- or 48-week Peginterferon/Ribavirin Duration"; March 31, 2011, 1:30 — 2:30 p.m. CET.

• #1202: "Characterization of HCV Variants in Non-SVR Patients in the REALIZE Study Suggests that Telaprevir Exhibits a Consistent resistance profile Irrespective of a Lead-in", April 2, 2011, 12:30 — 1:30 p.m. CET.

• #1244: "The Pharmacokinetic Interaction between Methadone and the Investigational HCV Protease Inhibitor Telaprevir"; April 2, 2011, 12:30 — 1:30 p.m. CET.

• #1245: "The Effect of Severe Renal Impairment on the Pharmacokinetics of the Investigational HCV Protease Inhibitor Telaprevir"; April 2, 2011, 12:30 — 1:30 p.m. CET.

• #1208: "Impact of Telaprevir-based Treatment Regimens on Fatigue in Genotype 1 HCV Treatment-naïve Patients: Results from ADVANCE and ILLUMINATE Studies"; April 2, 2011, 12:30 — 1:30 p.m. CET.

• #1242: "Long-term Follow-up of Chronic Hepatitis C Infected Patients Treated with Telaprevir: Evaluation of Persistence of Resistant Variants by Ultra-deep Sequencing"; April 2, 2011, 12:30 — 1:30 p.m. CET.

About Telaprevir and VX-222

Vertex has two oral medicines in late-stage development for the treatment of hepatitis C: telaprevir and VX-222. Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies. Vertex has received priority review for its applications for the approval of telaprevir by the U.S. FDA and Health Canada.

Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. VX-222 is currently being evaluated in combination with telaprevir, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.

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 Approximately 60 percent of genotype 1 hepatitis C patients who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7,8.9,10

More than 170 million people worldwide are chronically infected with hepatitis C. In the United States, up to 3.9 million people have chronic hepatitis C and of those, 75 percent are unaware of their infection.11 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.7 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.10

PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements regarding the data from clinical trials involving telaprevir and/or VX-222 that Vertex expects to feature in poster and oral presentations at EASL, March 30 to April 3, 2011. While Vertex believes these data will be presented at EASL, it is possible that future developments could adversely affect the content, timing or form of those presentations.

About Vertex

Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize 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.

For more information and to view Vertex's press releases, please visit http://www.vrtx.com/.

(VRTX - GEN)

References:

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 May 25, 2010.

2 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.

3 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.

4 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.

5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

6 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).

7 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.

8 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.

9 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.

10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.

11 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. 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 May 25, 2010.

Vertex Contacts:
Media:
Dawn Kalmar, 617-444-6992
or
Amy Pasqua, 617-444-6992
or
Zachry Barber, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057

Source: Vertex Pharmaceuticals

News Provided by Acquire Media

Source
03/07/2011

Emerging interventional techniques appear promising for the treatment of hepatic tumours, even those at advanced stages. Attendees at the special focus session on transarterial procedures, taking place today at ECR, will find out just how far these techniques, as well as combined approaches, have gone.

Surgery and liver transplantation are being widely used to treat hepatocellular carcinoma (HCC), incidence of which has increased steadily, particularly due to the spread of the hepatitis C virus.

For around 80% of liver cancer patients, surgical options are no longer viable once the disease has been diagnosed, which means the patients become candidates for interventional approaches. Radiofrequency (RF) ablation is an effective option for patients with early-stage HCC, particularly if the tumour is no larger than 3–5 cm in diameter. For patients at an intermediate or advanced stage, because HCC is highly chemoresistant, the traditional method of classical systemic infusion chemotherapy is not very effective.

Chemotherapeutic agents such as doxorubicin must thus be infused locally in high concentrations into the artery supplying the tumour. After local application using a catheter, arterial flow to the tumour must be blocked by embolisation. This method, transarterial chemo-embolisation (TACE), has shown promise in randomised trials. Furthermore, drug-eluting beads allow small particles to be loaded with the chemotherapeutic agent to transport doxorubicin directly into the tumour, blocking arterial flow at the same time. Results published from a European multicentre randomised study (Johannes Lammer et al, Cardiovasc. Intervent. Radiol. 2009) show improved outcome compared to conventional TACE. Drug-eluting beads used with doxorubicin are now attracting attention as a palliative life-prolonging treatment. Compared with conventional TACE, drug-eluting beads have significantly fewer adverse side effects because the therapeutic agent remains in the tumour and does not circulate in the patient’s body.

“In terms of therapy options, this is likely to be news to many radiologists. It’s important for them to know that even for patients with advanced tumours there is now a viable treatment,” said session moderator Prof. Johannes Lammer, director of cardiovascular and interventional radiology at Vienna’s Medical University.

Another study published last year in Cardiovascular Interventional Radiology by Dr. Katarina Malagari demonstrated that chemo-embolisation using drug-eluting beads was significantly better in terms of subjective patient response and time to progression compared to bland embolisation.

Also under evaluation in large European multicentre studies is another therapeutic option that involves radioembolisation using beta-emitting Yttrium particles injected into the tumour-feeding artery. This highly effective local radiation can kill the tumour cells without damaging the liver. Additionally, therapies combining TACE with drug-eluting beads and RF ablation are being studied in a multicentre randomised trial now in its second year.

“TACE can first reduce the size of the tumour, so that those patients who aren’t candidates for surgery, or whose tumours are a little too large for ablation, can still profit from curative ablation rather than palliative treatment,” Lammer said.

“The efficacy of a combination therapy, including RFA plus the intra-arterial administration of drug-eluting beads has been recently demonstrated, while the use of intravenously administered, thermally sensitive drug carriers is currently being explored,” added Professor Riccardo Lencioni, Director of Diagnostic Imaging and Intervention at Cisanello University Hospital in Pisa. Experimental studies in animal tumour models have shown that lowering the temperature threshold at which cell death occurs by combining sublethal heating with cell exposure to chemotherapeutic agents is an attractive alternate strategy for increasing tumour necrosis.

Despite the advances in local treatment, the long-term outcome of treated patients remains unsatisfactory because new tumours emerge within five years in about 80% of the cases. Adjuvant molecular targeted therapies with anti-angiogenic and anti-proliferative activity may prove useful in preventing early recurrence after successful ablation. Clinical trials of these methods are currently ongoing. Surgery remains the gold standard in HCC therapy. But if research over the next couple of years proves that a combined approach is effective, its routine use in the clinical setting will increase, to the benefit of patients, experts predict.

Source
CROI: Clinical Pharmacology of Boceprevir: Metabolism, Excretion, and Drug-Drug Interactions - (03/2/11)

CROI: Pharmacokinetic Interactions Between Antiretroviral Agents and the Investigational HCV Protease Inhibitor Telaprevir in Healthy Volunteers - (03/2/11)

from Jules of NATAP: the study was done in patients on Reyataz or efavirenz, darunavir and other protease inhibitors are not to be used right now with telaprevir due t drug drug interactions, although darunavir will be revisited, raltegravir interactions will soon be studied but an interaction with telaprevir is not expected.

- Early results from ongoing study showed that the hepatitis C virus was undetectable by week 4 in 70% of people treated with telaprevir-based combination therapy -

BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today interim results from an ongoing, two-part (A and B), Phase 2 study evaluating telaprevir in combination with pegylated-interferon and ribavirin compared to pegylated-interferon and ribavirin alone in people who are infected with both genotype 1 hepatitis C virus (HCV) and human immunodeficiency virus (HIV), also known as HCV-HIV co-infection. All people in this study were new to hepatitis C treatment. Part A of the study is evaluating telaprevir in people who are not currently being treated with antiretroviral therapy (ART) for HIV infection. Part B of the study is evaluating telaprevir in people receiving Atripla® or a Reyataz®-based regimen for HIV. These initial HIV regimens were selected based on current HIV treatment guidelines1 and data from drug-drug interaction studies of telaprevir and commonly used ART medicines. Data from the co-infection study were presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) taking place February 27 to March 2, 2011 in Boston.

The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. The interim analysis was conducted when all patients had reached week 4 of treatment. At that time, 70 percent (n=26/37) of people in the study (Parts A and B) who received telaprevir-based combination therapy had undetectable hepatitis C virus by week 4 (rapid viral response, RVR) compared to 5 percent (n=1/22) of people who received pegylated-interferon and ribavirin alone. HIV viral load and CD4 counts were stable among patients receiving a telaprevir-based regimen. Adverse events that occurred more frequently (≥10% difference) in the telaprevir arms compared to placebo were pruritus, nausea, dizziness, pyrexia, anorexia and vomiting. The majority of adverse events were mild or moderate.

"Research in hepatitis C has shown that people who respond early to treatment have a higher likelihood of achieving a viral cure," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These interim results are encouraging because they showed a high proportion of people in the study had a rapid viral response to telaprevir. We will use what we are learning from this study to inform the design of a Phase 3 co-infection study of telaprevir planned for the end of the year."

Interim Study Results

Sixty people were enrolled in this Phase 2 study. At the time of the analysis, all study participants had reached week 4 of treatment and 69 percent of patients (n=41/59) had completed a week 12 assessment. Data on one patient were not available when the analysis was performed. The preliminary results from this study are based on an interim analysis of 59 patients. For the purposes of this analysis, the 12-week results do not include patients who were still on treatment but had not yet reached the 12-week time point in the study.


Atripla (efavirenz, tenofovir disoproxil fumarate and emtricitabine): TVR was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): TVR was dosed at 750 mg, every 8 hours (q8h).

*RVR: rapid viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 4. **cEVR: complete early viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 12.

+12 weeks of telaprevir (TVR), Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV. ++48 weeks of PEG and RBV only for hepatitis C treatment.

The most common adverse events (≥15% of people) regardless of treatment arm were fatigue, pruritus, nausea, headache, dizziness, pyrexia, anorexia, vomiting, diarrhea and chills. Of these adverse events, pruritus, nausea, dizziness, pyrexia, anorexia and vomiting occurred more frequently in the telaprevir arms (≥10% difference) compared to placebo. The majority of adverse events were mild or moderate. Two people (n=2/14, or 14 percent) in a telaprevir-based treatment arm who were also receiving a Reyataz-based regimen discontinued part or all of the hepatitis C treatment regimen due to adverse events. There were no discontinuations due to adverse events in any of the other treatment arms. Final sustained viral response (SVR, or viral cure) results from this study in all 60 people are expected in 2012.

About the Ongoing Phase 2 Study

This study is a Phase 2, two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both genotype 1 hepatitis C virus and human immunodeficiency virus (HIV) who were new to hepatitis C treatment. The study enrolled 60 people. This interim analysis includes 59 people who received at least one dose of telaprevir or placebo and for whom data were available. The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. A secondary endpoint is to evaluate rates of SVR. The study is being conducted by Vertex in collaboration with Tibotec BVBA.

People in Part A and Part B of the study were randomized to receive either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n=13) of the study enrolled people who were not receiving antiretroviral therapy (ART) for the treatment of HIV. Part B (n=47) enrolled people who were being treated for HIV with either Atripla (n=24) or a Reyataz-based regimen (n=23). For people in Part B who were receiving Atripla, telaprevir was dosed at 1,125 mg every eight hours (q8h) based on drug-drug interaction data from a Phase 1 study. For people in Part B who were receiving a Reyataz-based regimen telaprevir was dosed at 750 mg every eight hours (q8h). The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services and International AIDS Society and drug-drug interaction studies of telaprevir and HIV medicines.

Additional Data Presented at CROI: Results from Multiple Phase 1 Drug-Drug Interaction Studies

Results from multiple Phase 1 studies evaluating the drug-drug interactions between telaprevir and commonly used HIV medicines were also presented at the CROI conference. The HIV medicines evaluated in these studies included ritonavir, ritonavir-boosted protease inhibitors, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) and a nucleotide analogue reverse-transcriptase inhibitor (NRTI). The ritonavir-boosted protease inhibitors studied were lopinavir, atazanavir, darunavir and fosamprenavir; the NNRTI was efavirenz and the NRTI was tenofovir.

Results from a Phase 1 study of telaprevir and ritonavir (Abstract #629)

· No significant boosting of telaprevir exposure by low-dose ritonavir was observed when telaprevir was given in combination with ritonavir. Results from multiple Phase 1 studies evaluating the interaction between telaprevir and ritonavir-boosted protease inhibitors, NNRTIs and NRTIs (Abstract #119)

· Telaprevir slightly increased the exposure to ritonavir-boosted atazanavir. Ritonavir-boosted atazanavir slightly reduced the exposure to telaprevir. This interaction was not considered to be clinically significant. A HIV regimen that includes ritonavir-boosted atazanavir is being evaluated in an ongoing Phase 2 study of telaprevir-based therapy in people infected with both hepatitis C and HIV.

· An interaction between efavirenz and telaprevir (750 mg, every eight hours) was observed, but a higher dose of telaprevir (1,125 mg, every eight hours) could largely offset the interaction. This higher dose of telaprevir is being evaluated as part of an ongoing Phase 2 study in people co-infected with hepatitis C and HIV who are also receiving efavirenz as part of their HIV treatment.

· Significant interactions were observed between telaprevir and boosted-lopinavir, darunavir and fosamprenavir, such that telaprevir-based combination therapy is not currently being evaluated for people taking these HIV medicines.

About Telaprevir

Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.

Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

Telaprevir has been granted priority review by the U.S. Food and Drug Administration (FDA) and by Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people chronically infected with genotype 1 hepatitis C virus (HCV). The applications include data from three registrational studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.

About Hepatitis C and HIV Co-Infection

There are 1 million people living with HIV in the United States.2 It's estimated that up to 30 percent of people living with HIV/AIDS are also infected with hepatitis C. 3 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death.3,4,5

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.6 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.6 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.6 Approximately 60 percent of genotype 1 hepatitis C patients who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,7,8,9 or viral cure.10 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.11,12,13,14,15

More than 170 million people worldwide are chronically infected with hepatitis C. In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.16 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.15 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.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.15 PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche. Reyataz® is a registered trademark of Bristol-Myers Squibb.

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

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 (i) the interim results being encouraging because they showed a high proportion of people in the study had a rapid response to telaprevir; (ii) Vertex's plan to use what it is learning from the study to inform a Phase 3 co-infection study of telaprevir planned for the end of 2011; (iii) expectations that final SVR results from the study will be available in 2012 and (iv) the possibility that a higher dose of telaprevir could largely offset the interaction observed between efavirenz and telaprevir. While Vertex 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, the risks that efforts to develop telaprevir as a treatment for patients co-infected with genotype 1 HCV and HIV may not proceed due to technical, scientific, commercial, financial or other reasons; that final outcomes, including SVR rates, from this clinical trial and any future clinical trials of telaprevir in patients with HCV-HIV co-infection may not be favorable; that RVR and cEVR may not be predictive of SVR in patients with HCV-HIV co-infection 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 http://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 aims to discover, develop and commercialize 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. For more information and to view Vertex's press releases, please visit http://www.vrtx.com/.

(VRTX - GEN)

References:

1 2010 Guidelines for Antiretroviral Treatment of HIV From the International AIDS Society-USA Panel JAMA. 2010;304(17):1897

2 Centers for Disease Control and Prevention. HIV/AIDS and Viral Hepatitis. Available at http://www.cdc.gov/hepatitis/Populations/hiv.htm. Accessed February 17, 2011.

3 Health Resources and Services Administration. Care and Treatment for Hepatitis C and HIV Co-infection. Available at http://hab.hrsa.gov/tools/coinfection/coinfectionsub.html and http://hab.hrsa.gov/tools/coinfection/index.html Accessed February 28, 2011.

4 Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999;30(4):1054-58.

5 Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.

6Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.

7 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 May 25, 2010.

8 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.

9 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. 10 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.

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12 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).

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16 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc. Source: Vertex Pharmaceuticals Incorporated
 
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