July 28, 2010

These computerized images show the innermost structure of a key bacterial enzyme that helps activate certain antibiotics and anti-cancer agents.

Public release date: 28-Jul-2010

Contact: Michael Bernstein
m_bernstein@acs.org
202-872-6042
American Chemical Society

Grown-ups aren't the only ones making exciting scientific discoveries these days. Two middle school students from Wisconsin joined a team of scientists who are reporting the first glimpse of the innermost structure of a key bacterial enzyme. It helps activate certain antibiotics and anti-cancer agents so that those substances do their job. Their study appears in ACS' weekly journal Biochemistry. The student co-authors of the study are from Edgewood Campus Middle School in Madison and participated in Project CRYSTAL, a special program that provides middle school students with hands-on laboratory experience.

In the report, study leader Hazel Holden and colleagues note intense scientific interest in a chemical process called methylation, which increases the activity of DNA, proteins, and other substances in the body by transferring methyl (CH3) groups to them. Special enzymes called methyltransferases make methylation possible, and these proteins are very important in a myriad of key biological processes.

Holden and colleagues studied a bacterial methyltransferase involved in the production of tetronitrose, a component of the promising anti-cancer agent, tetrocarcin, and the antibiotic kijanimicin. The methyltransferase seems to play a key role in activating these disease-fighters. The scientists identified the 3D structure of this methyltransferase, a key step in determining how it works and how it might be modified for potential use in medicine.

###

ARTICLE FOR IMMEDIATE RELEASE "Molecular Architecture of a C-3'-Methyltransferase Involved in the Biosynthesis of D-Tetronitrose"

DOWNLOAD FULL TEXT ARTICLE http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/bi100782b

CONTACT:

Hazel Holden, Ph.D.
Department of Biochemistry
University of Wisconsin
Madison, Wisc. 53706
Phone: 608-262-4988
Fax: 608-262-1319
Email: Hazel_Holden@biochem.wisc.edu

Source

Vertex has begun telaprevir FDA application

UPDATE 1-Vertex has begun telaprevir FDA application

Wed Jul 28, 2010 4:41pm EDT

* Rolling telaprevir FDA application underway

* Adjusted Q2 loss of 71 cents per share

LOS ANGELES July 28 (Reuters) - Vertex Pharmaceuticals Inc (VRTX.O) on Wednesday projected a wider-than-expected 2010 net loss and said its U.S. regulatory application for experimental hepatitis C drug telaprevir is underway.

Vertex said it now expects a full-year net loss of about $750 million, compared with a previous estimate for a net loss of about $700 million to reflect the timing of non-cash expenses and revenue related to its 2009 financial transactions as well as potential milestone payments.

On an adjusted basis, the company said it still expects a loss of around $600 million for the year.

For the second quarter, Vertex posted a net loss of $200 million, or $1.00 per share, compared with a net loss of $171.3 million, or 99 cents per share, a year earlier.

Excluding one-time items, Vertex said it lost 71 cents a share for the quarter.

The company said it is on track to complete the telaprevir FDA application in the second half of this year.

Source
 
Also See: Vertex Pharmaceuticals Reports Second Quarter 2010 Financial Results and Highlights Recent Business and Clinical Progress
Gastroenterology

Volume 139, Issue 1 , Pages 130-139.e24, July 2010

Kari E. Roberts, Steven M. Kawut, Michael J. Krowka, Robert S. Brown Jr, James F. Trotter, Vijay Shah, Inga Peter, Hocine Tighiouart, Nandita Mitra, Elizabeth Handorf, James A. Knowles, Steven Zacks, Michael B. Fallon

Received 2 December 2009; accepted 4 March 2010. published online 25 March 2010.

Abstract

Background & Aims
Hepatopulmonary syndrome (HPS) affects 10%–30% of patients with cirrhosis and portal hypertension and significantly increases mortality. Studies in experimental models indicate that pulmonary angiogenesis contributes to the development of HPS, but pathogenesis in humans is poorly understood. We investigated genetic risk factors for HPS in patients with advanced liver disease.

Methods
We performed a multicenter case-control study of patients with cirrhosis being evaluated for liver transplantation. Cases had an alveolar-arterial oxygen gradient ≥ 15 mm Hg (or ≥20 mm Hg if age > 64 years) and contrast echocardiography with late appearance of microbubbles after venous injection of agitated saline (intrapulmonary vasodilatation); controls did not meet both criteria for case status. The study sample included 59 cases and 126 controls. We genotyped 1086 common single nucleotide polymorphisms (SNPs) in 94 candidate genes.

Results
Forty-two SNPs in 21 genes were significantly associated with HPS after adjustments for race and smoking. Eight genes had at least 2 SNPs associated with disease: CAV3, ENG, NOX4, ESR2, VWF, RUNX1, COL18A1, and TIE1. For example, rs237872 in CAV3 showed an odds ratio of 2.75 (95% confidence interval: 1.65–4.60, P = .0001) and rs4837192 in ENG showed an odds ratio of 0.35 (95% confidence interval: 0.14–0.89, P = .027). Furthermore, variation in CAV3 and RUNX1 was associated with HPS in gene-based analyses.

Conclusions
Polymorphisms in genes involved in the regulation of angiogenesis are associated with the risk of HPS. Further investigation of these biologic pathways might elucidate the mechanisms that mediate the development of HPS in certain patients with severe liver disease.

Keywords: Genetic Polymorphism, Portal Hypertension

Abbreviations used in this paper: 95% CI, 95% confidence interval, AIM, Ancestry Informative Marker, CART, classification and regression trees, CAV3, Caveolin 3, COL18A1, collagen, type XVIII, α-1, D, linkage disequilibrium coefficient, EGF, epidermal growth, ENG, endoglin, ESR2, Estrogen receptor 2, HIF1A, Hypoxia-inducible factor 1, α subunit, HPS, hepatopulmonary syndrome, HWE, Hardy–Weinberg equilibrium, MELD, Model for End-stage Liver Disease, NOX4, NADPH Oxidase 4, OR, odds ratio, PaO2, partial pressure of oxygen in arterial blood, PC, principal component regression analysis, RUNX1, Runt-related transcription factor 1, SAT2, Spermidine/spermine N1-acetyltransferase family member, SHBG, Steroid hormone binding globulin, SNP, single nucleotide polymorphism, TIE1, Tyrosine kinase with Ig and EGF factor homology domains 1, VWF, von Willebrand factor

A listing of additional members of the Pulmonary Vascular Complications of Liver Disease Study Group can be found in Appendix 1.

Conflicts of interest The authors disclose no conflicts.

Funding Supported by NIH grants DK064103, DK065958, RR00645, RR00585, RR00046, RR00032, HL67771, HL089812 and, in part, under a grant with the Pennsylvania Department of Health, which specifically disclaims responsibility for any analysis, interpretations, or conclusions.

PII: S0016-5085(10)00463-4
doi:10.1053/j.gastro.2010.03.044
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source
-Hepatitis C: Rolling submission of New Drug Application underway; data from second pivotal Phase 3 trial - REALIZE - expected in the third quarter of 2010-

CAMBRIDGE, Mass., Jul 28, 2010 (BUSINESS WIRE) -- ---Cystic Fibrosis: Phase 3 registration program for VX-770 fully enrolled; data expected in first half of 2011-

---Financial: Vertex ends second quarter with cash position of approximately $980 million-

Vertex Pharmaceuticals Incorporated /quotes/comstock/15*!vrtx/quotes/nls/vrtx (VRTX 33.18, -0.01, -0.02%) today provided an update on recent progress in its development programs in hepatitis C virus (HCV) infection, cystic fibrosis (CF) and other diseases and reported consolidated financial results for the quarter ended June 30, 2010.

"We remain on track to complete the New Drug Application submission process for telaprevir later this year and to complete the buildout of our commercial function in advance of the potential launch of telaprevir," said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex Pharmaceuticals. "In the first half of this year, we established a seasoned commercial leadership team with broad experience in the area of infectious diseases, and we continue to bolster the internal infrastructure needed to support a field-based sales force for telaprevir and other potential future medicines.

"Our Phase 3 registration program in cystic fibrosis is now fully enrolled, positioning us for the planned submission of a New Drug Application for VX-770 in the second half of 2011. There is an urgent need for new and more effective therapies in cystic fibrosis, and we are committed to working toward improving the lives of people affected by this disease.

"As our development programs and commercial efforts advance, we remain focused on the management of our capital structure. We ended the second quarter of 2010 with a cash position of approximately $980 million, positioning us for continued investment in key activities to help support a successful potential launch for telaprevir," concluded Mr. Emmens.

Recent Clinical Development Progress

Telaprevir Phase 3 Program in Hepatitis C

-- Vertex expects efficacy and safety data from the supplemental Phase 3 ILLUMINATE trial to become available in August 2010, followed by efficacy and safety data from the pivotal Phase 3 REALIZE trial in September 2010.

-- The ILLUMINATE trial of telaprevir-based regimens is designed to evaluate the comparability of the sustained viral response (SVR), or viral cure, rates between the 24-week and 48-week treatment arms in treatment-naive people with genotype 1 hepatitis C who achieved undetectable virus levels at weeks 4 and 12 of treatment (eRVR) and who remained in the trial through week 20. Patients who met these criteria were randomized at week 20 to receive either 24 or 48 total weeks of therapy.

-- The REALIZE trial is being conducted by Vertex's collaborator Tibotec and is evaluating telaprevir in people with genotype 1 hepatitis C who did not achieve SVR, or a viral cure, with a prior pegylated interferon-based treatment, including difficult-to-treat null responder patients and patients who had a partial response or relapse in prior therapy. This is the only current Phase 3 trial of an investigational therapy for hepatitis C to enroll a difficult-to-treat patient population that includes patients who had a null response to a prior course of pegylated-interferon and ribavirin therapy.

-- Data from ILLUMINATE are expected to supplement the data obtained in the two pivotal Phase 3 trials of telaprevir - ADVANCE and REALIZE -- as part of the planned New Drug Application (NDA) submission for telaprevir.

Rolling NDA Submission Underway

-- Vertex recently submitted the Non-clinical and the Chemistry, Manufacturing and Controls (CM) sections of its NDA to the U.S. FDA as part of a rolling NDA submission for telaprevir. The company remains on track to complete the NDA submission for telaprevir in the second half of 2010.

Phase 3b Trial to Evaluate Twice-Daily (BID) Compared to Three-Times-Daily Dosing of Telaprevir

-- In the fourth quarter of 2010, Vertex and its collaborator Tibotec expect to initiate a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir (1,125 mg BID) compared to three-times-daily dosing of telaprevir (750 mg; q8h). This trial is expected to enroll approximately 700 treatment-naive people with genotype 1 hepatitis C in two telaprevir-based treatment arms and will be conducted in the U.S., E.U. and certain other countries. Based on advice from regulatory authorities in the U.S. and E.U., the trial will not include a control arm of pegylated-interferon and ribavirin.

Telaprevir/VX-222 Combination Trial

-- Vertex is currently conducting the first clinical trial to evaluate telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. This Phase 2 proof-of-concept trial is designed to evaluate SVR, or viral cure, rates using multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens that contain only telaprevir and VX-222. Vertex expects to obtain on-treatment clinical data from this trial in the second half of 2010.

Phase 3 Registration Program for VX-770

-- Three trials of the novel Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR) potentiator VX-770 are now fully enrolled as part of a global Phase 3 registration program focused on patients with the G551D mutation. These trials include the Phase 3 STRIVE trial in patients aged 12 years and older with the G551D mutation, the Phase 3 ENVISION trial in patients aged six to 11 years with the G551D mutation, and the Phase 2 DISCOVER trial in patients aged 12 and older homozygous for the F508del mutation.

-- Data from the Phase 3 registration program of VX-770 are expected in the first half of 2011.

Planned Combination Trial of VX-770 and VX-809

-- Vertex expects to initiate a Phase 2a clinical trial that will evaluate combination regimens of VX-809 and VX-770 later this year. The trial will enroll patients who are homozygous for the F508del mutation.

Proof of Concept Trials of VX-509 in Rheumatoid Arthritis and VX-765 in Epilepsy

-- Vertex is currently conducting Phase 2 proof-of-concept clinical trials of the novel caspase-1 inhibitor VX-765 in epilepsy and of the novel Janus kinase 3 (JAK3) inhibitor VX-509 in rheumatoid arthritis (RA).

-- Enrollment is complete in the trial of VX-765, and interim data are expected in the second half of 2010. Interim data from the trial of VX-509 are expected in 2011.

Second Quarter Results

For the quarter ended June 30, 2010, the Company's GAAP net loss was $200.0 million, or $1.00 per share, including certain charges totaling $57.5 million, compared to a GAAP net loss for the quarter ended June 30, 2009 of $171.3 million, or $0.99 per share, including certain charges totaling $42.0 million.

The non-GAAP loss, before certain charges, for the quarter ended June 30, 2010 was $142.5 million, or $0.71 per share, compared to $129.3 million, or $0.75 per share, for the quarter ended June 30, 2009. The increase in the Company's 2010 non-GAAP loss was principally attributable to an increase in total operating expenses as the company prepares for the potential launch of telaprevir and conducts a Phase 3 registration program for VX-770.

Total revenues for the quarter ended June 30, 2010 were $31.6 million, compared to $19.1 million for the second quarter of 2009. The increase is primarily attributable to higher collaborative revenues.

Research and development (R&D) expenses for the quarter ended June 30, 2010 were $155.1 million, compared to $139.3 million for the second quarter of 2009. The increase primarily reflects greater commercial supply investment for telaprevir.

Sales, general and administrative (SG&A) expenses for the quarter ended June 30, 2010 were $40.9 million, compared to $32.5 million for the second quarter of 2009. This increase reflects building of capabilities, including an increase in the number of employees and our commercial investments, to support advancement of telaprevir toward potential launch.

At June 30, 2010, Vertex had $979.1 million in cash, cash equivalents and marketable securities.

Full Year 2010 Financial Guidance

This section contains forward-looking guidance about the financial outlook for Vertex Pharmaceuticals.

The company is today reiterating its guidance for 2010 non-GAAP loss of approximately $600 million, as provided on February 4, 2010. The company is revising its guidance for 2010 GAAP net loss from approximately $700 million to approximately $750 million to reflect the timing of certain non-cash expenses and revenues related to the company's 2009 financial transactions and the milestone payments the company is eligible to earn from Janssen.

Non-GAAP Financial Measures

In this press release, Vertex's financial results are provided both in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, Vertex provides its second quarter 2010 and 2009 loss, and guidance for its projected 2010 loss, excluding stock-based compensation and executive transition expenses, restructuring expense, acquisition-related expenses, loss on exchange of convertible subordinated notes, and revenue and expenses related to certain September 2009 financial transactions. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the Company's business, are important in comparing current results with prior period results and provide additional information regarding its financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, and to manage the Company's business and to evaluate its performance. A reconciliation of the other non-GAAP financial results to GAAP financial results is included in the attached financial statements.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain.

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 expectation that the company will complete the NDA submission for telaprevir later in the year, (ii) the expectation that safety and efficacy data will be available from REALIZE in September 2010 and from ILLUMINATE in August 2010, (iii) the company remaining on track to complete the buildout of its commercial function in advance of the potential launch of telaprevir, (iv) the company being positioned to submit a New Drug Application for VX-770 in the second half of 2011, (v) the company's cash position positioning it for continued investment in key activities to help support a successful potential launch for telaprevir, (vi) the expectation that the ILLUMINATE data will supplement the data obtained from ADVANCE and REALIZE, (vii) the expectation that a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir will be initiated in the fourth quarter of 2010 and a Phase 2a clinical trial to evaluate combination regimens of VX-809 and VX-770 will be initiated later this year, (viii) the expected clinical trial designs for the Phase 3b clinical trial of telaprevir and the VX-809/VX-770 clinical trial, (ix) the anticipated timing of receiving clinical data from the Phase 3 registration program of VX-770 and from clinical trials of telaprevir/VX-222, VX-509 and VX-765 and (x) the company's guidance regarding 2010 GAAP and non-GAAP net loss. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes for each of its planned clinical trials and studies, and in particular its planned clinical trials of telaprevir, may not be favorable, that regulatory authorities may require supplemental clinical trials in order to support registration of telaprevir and/or VX-770, that planned or potential clinical trials may be delayed or may not be conducted, that the company may not be able to successfully develop telaprevir, VX-770, VX-509, VX-765 or combination therapies involving telaprevir and VX-222 or VX-770 and VX-809, that the company's expectations regarding its 2010 GAAP and non-GAAP net loss may be incorrect, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. The company disclaims any obligation to update the information contained in this press release as new information becomes available.

Source
28. July 2010 09:35

Intercept Pharmaceuticals, Inc., a clinical stage biopharmaceutical company developing novel therapeutics for chronic fibrotic and metabolic diseases, today announced the signing of a cooperative research and development agreement (CRADA) with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health to conduct a double blind, multi-center, study to evaluate the effects of obeticholic acid in patients with nonalcoholic steatohepatitis (NASH). Obeticholic acid is the generic name for INT-747, Intercept's first-in-class FXR agonist.

The planned study will enroll 280 patients at the eight U.S. centers constituting the NIDDK-sponsored NASH clinical research network (CRN), which will make it the largest study conducted in this disease. The objectives of the 72 week study will be to assess whether obeticholic acid improves histological disease activity and other disease markers, along with the safety of the drug in this patient population. The study is expected to begin in the fourth quarter of 2010 and the NIDDK will provide a majority of the funding needed under the CRADA.

NASH is a more serious form of nonalcoholic fatty liver disease (NAFLD) and occurs in patients who drink little or no alcohol. The disease is believed to be caused by abnormal metabolism of fats and, although it is often associated with obesity and insulin resistance, it also occurs in lean individuals. NASH is associated with fibrosis (scarring) in the liver that may lead to cirrhosis, liver cancer and death, and the disease also carries an additional risk of death due to heart disease. NASH is now the most common liver disease in the developed world, affecting at least 3 percent of the U.S. population, and there is no approved treatment for the disease.

Mark Pruzanski, MD, founder, President and CEO of Intercept, commented, "We are excited to collaborate with the NIDDK and CRN to test our drug in such a robust NASH study. Last year we presented data showing that obeticholic acid improved insulin sensitivity, lowered liver enzymes and induced weight loss in type 2 diabetic patients with NAFLD. These results and the novel mechanism of action of our drug are a promising basis for pursuing NASH."

Pat Robuck, PhD, MPH, the senior advisor for clinical trials in digestive and liver diseases, in the NIDDK's Division of Digestive Diseases and Nutrition, stated, "There is a huge unmet medical need in this patient population. The NIDDK, working together with our NASH CRN investigators, is committed to discovering effective and safe treatments for this serious disease. The preclinical and clinical data obtained so far with obeticholic acid suggest that it has beneficial effects on glucose metabolism and the liver, and the NASH CRN steering committee thinks it warrants rigorous clinical evaluation in NASH."

SOURCE Intercept Pharmaceuticals, Inc.

Source
Liver International
Early View (Articles online in advance of print)
Published Online: 8 Jul 2010
© 2010 John Wiley & Sons A/S

Seyed-Moayed Alavian 1 , Seyed Vahid Tabatabaei 1 , Maryam Keshvari 2 , Bita Behnava 1 , Seyyed Mohammad Miri 1 , Pegah Karimi Elizee 2 and Kamran Bagheri Lankarani 3

1 Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Iranian Blood Transfusion Organization Research Center (IBTO), Tehran, Iran
3 Shiraz University of Medical Sciences, Shiraz, Iran

Correspondence

Seyed-Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Ground floor of Baqiyatallah Hospital, Mollasadra Ave., Vanak Sq. P. O. Box 14155-3651, Tehran, Iran
Tel/Fax: +98 21 88 067 114
e-mail: editor@hepmon.com

KEYWORDS
congenital bleeding disorder • HCV • haemophilia • peginterferon α-2a • ribavirin

ABSTRACT

Background/aims: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV thrapy but there is little information about safety and efficacy of peginterferon α-2a and ribavirin combination therapy in these patients.

Material and methods: In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 μg of Pegasys® and 800–1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR).

Results: Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56–66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1–3.1), genotype non-1 OR=1.8 (95% CI 1.1–3.2), BMI<25 OR=2.1 (95% CI 1.3–3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1–3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation.

Conclusions: Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.

Received 9 February 2010
Accepted 24 May 2010

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1478-3231.2010.02296.x About DOI
 
Source
from Jules: In an attempt to create controversy the NY Times writer Andrew Pollack in an article published in the NY Times on July 21 where he talks about the new HCV drugs in development prints some very inflammatory & incorrect information. While at the same time appearing to say it is good that new more effective HCV drugs are in development that will save people's lives, he quotes a Dr Koretz who is based in LA and apparently not a hepatitis doctor as saying 'there is no good evidence that HCV treatment makes a difference since many patients cured might never develop serious liver disease'. This expresses an incorrect & irresponsible misunderstanding of hepatitis C care & treatment, it ignores much of the published and well known facts and does a disservice to patients & the entire health system. Over 4 million people in the USA are estimated to have hepatitis C virus (HCV). Many have been infected for 30 years or longer. A recently published paper by a well respected hepatitis researcher and doctor Gary Davis based at Baylor University in Texas reported in a model how the many people infected with HCV over 20 years ago are now aging and in these people the disease has progressed to serious disease where there is much greater increased risk for liver cancer and dying from the disease. This is true. The disservice by the Times article is that it discourages individuals from getting tested to see if they have HCV, because if you don't know you have HCV you certainly will not see a clinician to receive further care. It is known that 75% of HCV-infected individuals in the USA do not know they have HCV. Many individuals have died of liver disease and liver cancer because they were not tested. Once diagnosed with HCV an individual can then receive advise from a good doctor regarding whether they should be treated or if they can defer treatment, they can be monitored over years to see if the disease is progressing or not, they can improve their lifestyle to take better care of their health & liver, and they can make informed decisions about treatment. We need a large national HCV screening/testing program throughout the USA, particularly in major urban cities, as HCV very disproportionately affects African-Americans & Latinos, the health disparities are enormous. At the cost of The abandoning ethical reporting the Times reporter chose to create harmful controversy, as reporters sometimes do. The costs of many people getting sick from HCV to the governments in the USA will be enormous as large numbers of patients age with HCV and develop serious liver disease, costs for hospitalizations will zoom. If tested and in care not all patients require treatment but they can at least make informed decisions. Jules Levin, NATAP

Aging of Hepatitis C Virus (HCV)-Infected Persons in the United ...
Stacked prevalence curves showing number of cases by year with cirrhosis according to gender and age at time of initial hepatitis C virus infection. ...
www.natap.org/2010/HCV/031110_02.htm

Hope Against Hepatitis C, New Drugs - 'this will be revolutionary' - (07/19/10)
New cases of liver cancer are already rising year by year. And hepatitis C is the leading cause of liver transplants, like the one recently received by the rock musician Gregg Allman.

Hopes for new treatments were buoyed in May by the first results from a late-stage clinical trial of one of the new drugs, telaprevir from Vertex. When added to the existing treatment - a combination of alpha interferon and ribavirin - telaprevir effectively cured 75 percent of patients, compared with 44 percent of those treated with the existing drugs alone. And for many patients, the course of treatment could be halved to 24 weeks.

Dr. Poordad, who is a consultant to some of the pharmaceutical companies, said that one-fifth of his patients were being "warehoused," meaning they were forgoing treatment now to wait for the new drugs.

"I think the companies have done a superb job of marketing this disease," said Dr. Ronald L. Koretz, emeritus professor of clinical medicine at the University of California, Los Angeles. Dr. Koretz said there was no good evidence that treatment made a difference since many patients cured by the drugs might never have developed serious problems anyway.

NVHR Responds to New York Times Article on Hepatitis C Testing

WASHINGTON, July 22 /PRNewswire-USNewswire/ -- In response to today's New York Times article, "Hope against Hepatitis C," Andrew Muir, M.D., M.H.S., Director, Gastroenterology/Hepatology Research, Duke Clinical Research Institute and Steering Committee Member of the National Viral Hepatitis Roundtable (NVHR) released the following statement:

"Today's New York Times article details potential promising new drug therapies that could significantly improve the way we treat individuals infected with hepatitis C. Regrettably, the article suggests that expanded screening for hepatitis C may not be warranted. This approach is wrong and contrary to the direction in which we should and must move our health care system, particularly through improved access to care under health care reform. More than 5 million Americans are estimated to be infected with viral hepatitis B or C - and most are unaware they are infected as there are often few symptoms. Our health care system misses most infected individuals, who only learn that they have hepatitis C once they have progressed to liver cancer, cirrhosis, or liver failure. At that juncture, treatment options are limited and success rates are lower.

"Precisely because we do not know which individuals with hepatitis C will advance to these terrible diseases, it is critical that our public health infrastructure be modernized to achieve early detection of new infections and also to screen for individuals within specific risk groups, such as baby boomers and disproportionately affected populations. Once individuals are aware of their status, they will be empowered with this information, not only to make treatment choices, but also lifestyle choices to decrease their likelihood of disease progression and not to spread this infectious disease to others. In our current health care system, there are far too few options for diagnosis, care, and treatment. Unless or until the health care system provides access to all persons in need of hepatitis C treatment, it is important for the pharmaceutical industry to provide comprehensive compassionate care programs for those who are un/under insured.

"We can't prevent or treat what we don't know, which is why screening is critical. Access to screening would capture more infected individuals who can respond favorably to early intervention, reduce transmission, avoid needless medical expenses, and ultimately save thousands of lives annually."

NVHR is a coalition of more than 150 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/

SOURCE National Viral Hepatitis Roundtable

Source

Opportunities for the hepatitis C therapeutics market in Australia

28 July 2010

Spirited efforts in Australia to raise awareness of hepatitis C have increased the number of diagnosed cases and expanded the base of patients available for treatment, thus enabling the introduction of novel treatments in this market sector, says a new multi-client report from Frost & Sullivan.

Physicians expect the rate of diagnosis to continue rising in Australia due to heightening of awareness among general practitioners regarding screening and treatment for hepatitis C. Screening of patients in Australia, especially among illicit drug users, has resulted in a spike in the number of diagnosed cases of hepatitis C virus (HCV). In 2009, an estimated 77% of patients-at-risk with hepatitis C were diagnosed, notes F&S, and this figure is expected to reach up to 87% by 2016.

New anti-virals set to come to market

Higher efficacy and safety are the most preferred drug attributes. Physicians expect new oral anti-virals (boceprevir and telaprivir) and interferon with improved safety (albuferon) to be launched by 2013 in Australia. According to physicians, prevalence had increased rapidly in the early 2000s, but the rate had declined over the years and the pace is likely to slacken in the future owing to a major disruption to the supply of heroin in Australia in 2001.

"The Australian government has unleashed Initiatives to address the Hepatitis C virus in the country, allocating $14.3 million (A$17 million) for hepatitis C education and prevention over the 2007-2011 period," notes an F&S analyst, adding: "State and territory governments also have substantial budgets for hepatitis C prevention and education."

The priority action areas identified as part of the National Hepatitis C Strategy are prevention, education; diagnosis, treatment, surveillance; and research. The government is avidly addressing health care workforce development as well as issues surrounding discrimination and stigma.

Only 3% of diagnosed patients pursuing treatment

Although there is a high diagnosis rate in Australia, only a paltry 3% of diagnosed patients pursue treatment owing to a lack of patient understanding about treatment options. According to physicians, one of the main reasons for such a large proportion of diagnosed patients left untreated is that they are predominantly from disadvantaged groups such as illicit drug users, aboriginal people, those serving prison sentences, and some migrant groups, which do not have access to conventional healthcare.

Often the reason is real or perceived stigma and discrimination. Aside from this, there is a great deal of angst about debilitating side effects, frequent dosing, and lackluster efficacy of the existing HCV treatments, especially for those afflicted with genotype 1. Moreover, there is a belief that a liver biopsy is required to receive treatment, which deters patients from undergoing treatment.

To circumvent the challenges clouding the market landscape, companies must offer treatment options that expedite efficiency, have fewer side effects and are cost efficient, states F&S. Patients should be made aware of their disease status and encouraged to remain compliant. "As more improvements are required to educate at-risk patients, public and private organizations - including pharmaceutical companies - must up the ante to spread awareness," notes the analyst, stressing that "greater information outreach will help patients obtain the right mode of treatment and, ultimately, stem the onslaught of the hepatitis C virus in Australia."

Source
-- PSI-938 single ascending dose study in healthy volunteers supports progression to 7 day monotherapy study in HCV infected patients
-- PSI-938 was generally safe and well tolerated with no dose-limiting toxicity

-- Further results from single ascending and multiple ascending dose trials are expected in the third quarter 2010

PRINCETON, N.J., July 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that safety and pharmacokinetic data from the PSI-352938 ("PSI-938") single ascending dose study support progression to a multiple ascending dose trial with PSI-938, which has initiated dosing. PSI-938 is a guanine nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. This study is designed to assess the safety, tolerability and antiviral activity of PSI-938 monotherapy administered over 7 days in HCV-infected individuals.

"PSI-938 is the third differentiated nucleoside analog that Pharmasset has advanced into clinical development for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "As with RG7128 and PSI-7977, PSI-938 demonstrates a high barrier to resistance in vitro; but unlike the cytidine and uridine analogs, PSI-938 retains equivalent potency against the S282T mutant. As the HCV field moves toward IFN-sparing, all-oral DAA combinations, we continue to believe nucleosides could become the backbone of care given these differentiating attributes and have the potential to be combined with all DAA classes."

PSI-938 Phase 1 Program Overview

The Phase 1 program is investigating the safety, tolerability and pharmacokinetics of PSI-938 in healthy subjects following escalating single doses (Phase 1a), and in patients chronically infected with HCV genotype 1 following repeat dosing for 7 days (Phase 1b). The Phase 1b study will additionally investigate hepatitis C viral dynamics and monitor for the development of drug resistance.

Subjects in the Phase 1a single ascending dose study received single doses of PSI-938 ranging from 100 mg to 800 mg or a matching placebo. Preliminary data from the phase 1a single ascending dose study includes:

•No serious adverse events or discontinuations;
•No dose-related adverse events or dose-limiting toxicity;
•No grade III / IV lab abnormalities;
•No clinically significant changes in vital signs or ECGs; and
•PK which supports QD dosing.

A Phase 1b multiple ascending dose trial has now been initiated in treatment-naïve patients with chronic HCV genotype 1 infection. Subjects will be enrolled at multiple centers in the US and randomized to PSI-938 or placebo. Based upon the results from the first time in human study, the first dose of PSI-938 to be tested will be 100 mg administered once daily. The primary objectives of this study are to assess the safety, tolerability, pharmacokinetics and viral dynamics of PSI-938 after repeat dosing over 7 days.

Results from both studies are expected in the third quarter of 2010.
Purine and Pyrimidine Analogs

Pharmasset's purine nucleoside/tide analogs share many of the benefits of pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7977, in that they have demonstrated in vitro activity across multiple HCV genotypes, have a higher barrier to resistance than other classes of HCV small molecules in development, and, in spite of the prodrug technology, have no CYP 3A4 liability and thus a lower risk of drug interactions when combined with other direct acting antivirals targeting HCV. In addition, Pharmasset's purine analogs retain equivalent potency against wild type HCV and virus with the S282T mutation associated with in vitro resistance in other nucleoside/tide analogs in development. Furthermore, the purines are metabolized to the active triphosphate form through a different phosphorylation pathway than the pyrimidine analogs, thus decreasing the risk of competition between the two analogs for conversion to the active triphosphate. Given these characteristics, Pharmasset's purine and pyrimidine analogs have the potential to be combined as part of a future treatment regimen, which will be the focus of upcoming trials.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV) and, secondarily, on the development of Racivir(TM) for the treatment of human immunodeficiency virus (HIV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently completed a Phase 2a study, and PSI-938, an unpartnered guanine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.

Pegasys® and Copegus® are registered trademarks of Roche.

Contact

Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
richard.smith@pharmasset.com
Office: +1 (609) 613-4181

Forward-Looking Statements


Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," including, without limitation, statements that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2009 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009 and March 31, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.

SOURCE Pharmasset

Source

New Transplantation Criteria for Liver Cancer Patients

ScienceDaily (July 28, 2010) — Researchers at the University of California, San Francisco propose that treatments used on liver cancers beyond the established Milan criteria for liver transplantation may be appropriate for all patients with hepatocellular carcinoma (HCC) who are listed for transplantation

Full details appear in the August issue of Liver Transplantation, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

According to the American Cancer Society, about 90% of adult primary liver cancers are hepatocellular carcinomas. In 2009, an estimated 22,620 adults in the U.S. were diagnosed with primary liver cancer with 18,160 deaths expected to occur this year from HCC. Liver cancer is the sixth most common cause of cancer death among men, and ninth most common cause of cancer death among women.

Liver transplantation is an important treatment option for selected patients with non-resectable HCC. The Milan criteria provide guidelines to qualify HCC patients for liver transplantation and include one tumor smaller than 5 cm or up to 3 tumors smaller than 3 cm, no extrahepatic manifestations, and no vascular invasion. The Milan criteria were adopted because it identified a population with excellent outcome potential following transplantation -- roughly equivalent to patients transplanted without HCC. However, HCC incidence is expected to increase and researchers are investigating whether the criteria for liver transplantation should be expanded to make even more patients eligible.

The San Francisco researchers suggest that the Milan and other criteria have proved inadequate. Team leader Dr. John Roberts explains, "It has not been shown there is any particular size of tumor that represents a 'no risk' of recurrence, at least among those tumors that can be detected radiologically. Further, the degree of risk is not the same for all patients within the Milan criteria."

Dr. Roberts points out that tumor size and number are only surrogate markers for underlying tumor biology and that using another marker -- tumor behavior over time -- allows the biology of the tumor to become apparent, dictating the most appropriate treatment strategy.

The UCSF team has taken a 'down staging' approach for patients with large tumors. This involves radiofrequency ablation, chemoembolization or both to control the tumor and then a requisite waiting period to determine tumor biology over time as the development of extra-hepatic or intra-hepatic spread is observed. This paradigm results in about 30% of the patients being ineligible for transplantation because of HCC progression, but those who make it to transplantation have an excellent outcome as compared to patients transplanted with tumors beyond the Milan criteria who are not treated. The median time between the first ablative procedure and transplantation was 8.2 months with a range of 3-25 months. This approach suggests that the test of time may be the surest method to select patients with HCC who are destined to have good transplant outcomes. Dr. Roberts argues that this approach, ablating the tumor and waiting, should be expanded to all patients listed for transplantation with hepatocellular carcinoma as the test of time can eliminate from transplantation patients whose disease is likely to recur after transplantation.

"Our experience with ablative treatment and then observation suggests that the ultimate outcomes of transplantation are not dependent on the primary tumor but more on time spent waiting for transplantation," Dr. Roberts concluded. "It would seem logical that smaller and/or fewer tumors, though more unlikely to have spread, would also benefit from a period of time if the primary tumor can be controlled. The waiting period may be able to decrease the 10% recurrence rate seen in patients transplanted within Milan."

Source