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Week Ending: September 15th , 2007
Alan Franciscus
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This Issue:
September 8th, 2007
Gilead eyes drug cocktails in hepatitis C fight
http://www.therapeuticsdaily.com
By Lisa Baertlein
FOSTER CITY, Calif. (Reuters) - HIV drug maker Gilead Sciences Inc is targeting hepatitis C and expects the liver infection to be fought, like HIV, with cocktails that include various drugs, Chief Executive John Martin told Reuters on Thursday.
"Hepatitis will surely be a combination market like HIV," said Martin, whose company has made its mark by combining multiple HIV drugs into a single pill, which makes it easier for people with HIV to comply with their treatment.
Hepatitis C is a blood-borne virus that destroys the liver and affects roughly 4 million people in the United States. The infection is also linked to liver cancer, a hard-to-treat and deadly disease.
Gilead, which saw product sales rise 43 percent in 2006 to $2.59 billion on strength in its HIV business, is investing heavily in treatments for hepatitis C, which like HIV has a high mutation rate that contributes to drug resistance.
Competition is fierce in the emerging market for treating hepatitis C. Yet recent failures of experimental drugs from Idenix Pharmaceuticals Inc and ViroPharma Inc illustrate the difficulty of developing new treatments for the disease, which is spread via blood and bodily fluids.
Closely watched experimental drug telaprevir, or VX-950, from Vertex Pharmaceuticals has the potential to improve treatment of the disease and potential rivals include Schering-Plough's boceprevir, or SCH 503034, as well as Gilead's GS-9190.
"The game's not over," Martin said in an interview at Gilead's headquarters in Foster City, south of San Francisco.
Martin said quite a few HIV drugs work as treatments for hepatitis B, which is more prevalent in Asia and also has been linked to liver cancer.
Gilead said in June that a late-stage clinical trial showed its drug Viread, currently approved to fight HIV, met its main goal of reducing viral levels and liver inflammation in patients with chronic hepatitis B.
Hepatitis B, also blood-borne and controlled in part through vaccination, is believed to affect more than 1 million Americans and an estimated 400 million people worldwide.
Martin said Gilead continues work on its experimental HIV drug that shares the same mechanism as Merck & Co's Isentress, which a U.S. regulatory panel on Wednesday recommended for approval to treat HIV patients who have failed other treatments.
Merck's drug, also known as raltegravir, is the first HIV treatment to block an enzyme called integrase that is required for replication of the HIV virus.
Martin said he hopes Gilead's drug, elvitegravir, or GS-9137, will one day grab share in the market for treating late-stage HIV.
While Isentress is taken twice daily, He added, Gilead's rival product is being developed as a once-daily therapy so it may eventually be combined into a pill with other drugs.
Gilead shares, which rose 3 percent to close at $37.59 on the Nasdaq on Thursday, are up 16 percent so far this year.
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September 10th, 2007
Body Shop founder dies, aged 64
http://www.nzherald.co.nz
LONDON - Anita Roddick, founder of beauty retailer The Body Shop and one of Britain's best known businesswomen, has died at the age of 64 after suffering a major brain haemorrhage, her family said.
Roddick founded The Body Shop in Brighton in 1976, selling toiletries made from natural ingredients, and her brand became a byword for socially and environmentally responsible business.
The daughter of Italian immigrants, Roddick saw her business mushroom into an empire of more than 2,000 stores serving more than 77 million customers in 51 different markets. She sold her stake in The Body Shop to France's L'Oreal last year.
"Anita Roddick was admitted to St Richard's Hospital in Chichester, close to her home, yesterday evening when she collapsed after complaining of a sudden headache," her family said in a statement.
"Mrs Roddick was admitted to the hospital's Intensive Care Unit and her husband Gordon and two daughters, Sam and Justine, were with her when she died," it said.
A multi-millionaire, Roddick campaigned against human rights abuses and was an environmental activist. The mission statement of The Body Shop was: "To dedicate our business to the pursuit of social and environmental change."
Roddick said it was her mother's frugality during World War Two that inspired her to campaign for environmental issues and question retail conventions.
"We reused everything, we refilled everything and we recycled all we could. The foundation of The Body Shop's environmental activism was born out of ideas like these," she wrote on her Web site.
"The Body Shop is not, and nor was ever, a one-woman-show -- it's a global operation with thousands of people working towards common goals and sharing common values," she said.
Roddick revealed earlier this year that she was suffering from liver damage after contracting the Hepatitis C virus more than 35 years ago and soon began campaigning for support for sufferers of the potentially deadly disease.
She developed Hepatitis C from infected blood given to her during the birth of her youngest daughter, Sam, in 1971.
- Reuters
RODDICK'S MISSION STATEMENT
Anita Roddick explains the raison d'etre for her commercial and humanitarian efforts:
"I started The Body Shop simply to create a livelihood for myself and my two daughters while my husband, Gordon, was trekking across the Americas. I had no training or experience and my only business acumen was Gordon's advice to take sales of £300 a week. Nobody talks of entrepreneurship as survival, but that's exactly what it is and what nurtures creative thinking. Running that first shop taught me business is not financial science, it's about trading: buying and selling.
"It's about creating a product or service so good that people will pay for it. Now 28 years on The Body Shop is a multi-local business with over 1,980 stores serving over 77 million customers in 50 different markets in 25 different languages and across 12 time zones. And I haven't a clue how we got here!
"It wasn't only economic necessity that inspired the birth of The Body Shop. My early travels had given me a wealth of experience. I had spent time in farming and fishing communities with pre-industrial peoples, and been exposed to body rituals of women from all over the world. Also the frugality that my mother exercised during the war years made me question retail conventions. Why waste a container when you can refill it? And why buy more of something than you can use? We behaved as she did in the Second World War, we reused everything, we refilled everything and we recycled all we could. The foundation of The Body Shop's environmental activism was born out of ideas like these.
"I am aware that success is more than a good idea. It is timing too. The Body Shop arrived just as Europe was going 'green'. The Body Shop has always been recognizable by its green color, the only color that we could find to cover the damp, moldy walls of my first shop. I opened a second shop within six months, by which time Gordon was back in England. He came up with the idea for 'self-financing' more new stores, which sparked the growth of the franchise network through which The Body Shop spread across the world. The company went public in 1984. Since then, I have been given a whole host of awards, some I understand, some I don't, and a couple I think I deserve.
"Businesses have the power to do good. That's why The Body Shop's Mission Statement opens with the overriding commitment, "To dedicate our business to the pursuit of social and environmental change." We use our stores and our products to help communicate human rights and environmental issues.
"For me, campaigning and good business is also about putting forward solutions, not just opposing destructive practices or human rights abuses. One key area where my business and personal interests naturally combine is through The Body Shop Community Trade initiatives. It all started in 1989 when I attended the gathering at Altamira of Amazonian Indian tribes protesting against a hydro-electric project which would have flooded thousands of acres of rainforest, submerging native lands. There had to be something practical I could do to help these people preserve their environment and culture. Nuts? Specifically Brazil nuts, which the Indians gathered sustainably from the forest and which when crushed produce a brilliant oil for moisturizing and conditioning. This first trading relationship with forest people, unused to any real commercial activity, was fraught with pitfalls and dangers. But 13 years on we're still trading with them and have even set up a Green Pharmacy project producing remedies based on traditional knowledge of forest plants - reducing dependency on inappropriate and expensive modern pharmaceuticals.
"In November 1999 I visited our long-term partners Teddy Exports in southern India and GPI in Nepal and our new partners, the Chepang indigenous people who grow herbs for our Ayurvedic range. In January 2001 I visited the 130 sesame seed oil farmers in Nicaragua who receive a fair and stable price for their seed. As a result the farmers have built up a sustainable business that as well as offering marketing clout, runs a subsidized store, a credit union, and employs a Cuban agronomist specializing in organic methods. The deal with The Body Shop isn't going to make the farmers financially rich, but it does enable them to maintain their chosen way of life and through co-operation achieve autonomy. I'm immensely proud of our efforts to make fair or community trade relationships more mainstream. The Body Shop now has 42 such projects in 26 countries and we aim to develop more.
"The Body Shop and I have always been closely identified in the public mind. Today, it is impossible to separate the company values from the issues that I care passionately about - social responsibility, respect for human rights, the environment and animal protection, and an absolute belief in Community Trade.
"But The Body Shop is not, and nor was ever, a one-woman-show - it's a global operation with thousands of people working towards common goals and sharing common values. That's what has given it a campaigning and commercial strength and continues to set it apart from mainstream business."
SOURCE: www.bodyshop.com
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Medivir: Preclinical Data Presented on New Hepatitis C Protease Inhibitor
http://biz.yahoo.com
STOCKHOLM, Sweden--(BUSINESS WIRE)--Regulatory News: Tibotec and Medivir (STO:MVIRB) scientists will jointly present the first preclinical data on TMC435350 at the 14th International Symposium on Hepatitis C Virus and Related Viruses in Glasgow, Scotland later this week.
The poster by Simmen et al. entitled "Preclinical Characterization of TMC435350, a novel macrocyclic inhibitor of the HCV NS3/4A serine protease" demonstrates the ability of the compound to reduce the amount of Hepatitis C virus (HCV) replication in laboratory replicon experiments via protease inhibition. Combination of TMC435350 with interferon is also reported to enhance RNA reduction (greater than 4 logs reduction in the replicon model), and to suppress the appearance of drug-resistance. Given its in vitro antiviral activity and encouraging preclinical drug-like profile, TMC435350 is currently undergoing phase I clinical trials.
The phase I program commenced in Europe in February 2007. The first clinical safety and pharmacokinetic data will be presented later this year at the AASLD Liver Meeting in Boston.
For further information on Medivir, please see our website: www.medivir.se
This information was brought to you by Cision http://newsroom.cision.com
Contact:
Medivir
Rein Piir, CFO & VP, Investor Relations,
+46 8 5468 3123 or +46 708 5327 292
Source: Medivir
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September 11th, 2007
Pharmasset says hepatitis C drug meets trial goals
http://www.pharmaceutical-business-review.com
By Sarah Routledge
Pharmasset has reported preliminary safety and potent antiviral activity with its investigational drug following 14 days of monotherapy in 40 patients chronically infected with hepatitis C virus who had failed prior interferon therapy.
The candidate, R7128, is a prodrug of PSI-6130, an oral cytidine nucleoside analog polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. The Phase I multiple ascending dose study of R7128 was designed to evaluate safety, tolerability, pharmacokinetics and preliminary antiviral activity.
R7128 demonstrated potent, dose-dependent antiviral activity across the four patient cohorts receiving 750mg or 1500mg administered either once-daily or twice-daily for 14 days as monotherapy. The greatest mean decrease in HCV RNA from baseline was demonstrated in the patient cohort that received 1,500mg twice-daily, the highest dose of R7128 administered in this study. These patients demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of viral rebound in any dose cohort during the 14 days of dosing.
R7128 was generally safe and well tolerated in this Phase I multiple ascending dose study. There were no serious adverse events, no adverse events requiring dose modification, no dose-related gastrointestinal adverse events and no clinically significant changes in vital signs, electrocardiograms, hematologic, renal or other laboratory parameters.
Based on the results of this study, Pharmasset and Roche plan to initiate a 28-day study of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in treatment-naive patients chronically infected with HCV genotype 1. Patient recruitment for this combination study is expected to begin in late September 2007.
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Prolonged Interferon Therapy May Prevent Progression of Hepatitis C to Cancer
http://www.medscape.com
NEW YORK (Reuters Health) Aug 31 - Prolonged interferon therapy reduces the progression of chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC), according to a report in the August issue of the Journal of Medical Virology.
Dr. Yasuji Arase and associates from Toranomon Hospital in Tokyo evaluated the effect of long-term interferon therapy on the development of HCC in 120 patients aged 60 years and older with chronic HCV-related hepatitis or cirrhosis.
These patients received 3 million units natural interferon-alpha two or three times weekly for up to 15.5 years. Another 240 similar patients treated with herbal medicines served as controls.
Serum alpha-fetoprotein (AFP) and transaminase levels decreased significantly in patients treated with interferon compared with patients not treated with interferon, the authors report.
The cumulative rates of HCC were significantly lower in the interferon group than in the interferon group at 5 years (5.9% versus 13.7%, respectively) and at 10 years (17.1% versus 32.8%, respectively), the report indicates.
In a multivariate analysis, not being treated with interferon, having advanced histological staging, and having serum AFP levels above 10 ng/mL after initiation of treatment were independently associated with a higher risk of progression to HCC.
Only 9 of 120 interferon-treated patients discontinued therapy because of adverse events.
Based on these findings, the researchers conclude, "Long-term interferon treatment for protection against HCC could be recommended for patients with elevated AFP levels and/or severe liver fibrosis who can tolerate interferon-related side effects."
J Med Virol 2007;79:1095-1102.
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HBV and HIV Responses Linked in Coinfected Patients
www.medscape.com
NEW YORK (Reuters Health) Sept 03 - New research shows that hepatitis B virus early antigen (HBeAg) or HBV surface antigen (HBsAg) seroconversion is associated with a sustained HIV response during antiretroviral therapy.
HBV coinfection is common among HIV-infected patients, but the natural history of chronic hepatitis B in this setting and the impact of highly active antiretroviral therapy (HAART) has on HBeAg and HBsAg seroconversion is unclear, according to the report in the September 1st issue of Clinical Infectious Diseases.
Dr. Patrick Miailhes, from Hopital-Dieu in Lyon, France, and colleagues addressed this topic by analyzing data from 92 coinfected patients. Eighty-two of the patients received antiretroviral therapy, including 79 treated with HAART. Seventy-six patients received lamivudine.
Lamivudine-resistance mutations developed in 28 of the patients given the drug, the report indicates.
During treatment with antiretroviral therapy, anti-HBeAg antibodies developed in 10 of 59 HBeAg-positive patients, HBsAg clearance occurred in 3 of 10 patients, and anti-HBsAg antibodies developed in 2 of 3 patients. Of 23 HBeAg-negative patients, 2 cleared HBsAg and developed anti-HBsAg antibodies.
Seroconversion of HBeAg, HBsAg, or both in combination with undetectable HBV DNA was tied to a sustained HIV response (p = 0.001), shorter duration of antiretroviral therapy, and with more severe disease, the report indicates.
The HBV response was directly related to the increase in CD4+ cell count seen in HAART-treated patients with elevated baseline levels of alanine aminotransferase.
In a related editorial, Dr. Hans L. Tillmann, from the University of Leipzig in Germany, writes that the study yielded some surprises. For instance, a shorter course of antiretroviral therapy was actually linked to higher rates of HBeAg and HBsAg seroconversion. Also, patients with low CD4+ cell counts and those with AIDS had higher conversion rates than patients with earlier HIV disease.
He concludes that further research is needed to understand the basis for these findings. However, he also emphasizes that "preventing HBV infection is better than treating it" and notes that "every HIV-infected patient should be screened for HBV infection and offered vaccination in the instance of negative results for HBV markers."
Clin Infect Dis 2007;45:624-636.
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Body art shops could be regulated
http://www.contracostatimes.com
By Chris Metinko
STAFF WRITER
ALAMEDA: Few safety standards are in place for tattoo and piercing shops
Alameda County health officials want to make sure people who receive a new tattoo or piercing at body art shops leave with only that -- and not with hepatitis B or other some other infection.
Members of the county's Environmental Health Department on Monday proposed a new ordinance for body art and piercing establishments to the board of supervisors' health committee.
The proposed ordinance would establish health and safety standards for body art and body piercing shops within unincorporated Alameda County. It also would require all such businesses to obtain an operation permit that would have to be renewed annually.
"Personally, I'm happy to see you doing this," said Supervisor Alice Lai-Bitker, who is chairwoman of the committee. "You see more and more people getting into body art and piercing. I'm really for this."
Few regulations are placed on body art and piercing shops. Under state law, all body art establishments and the artists therein must register with their county environmental health departments. However, the state Department of Health Services has been unable to develop statewide standards.
The lack of state action has caused many counties, including San Francisco, Santa Clara, San Mateo and Monterey, to establish their own standards. The proposed Alameda County ordinance would be similar to those counties' rules, which cover everything from faucet controls, floor conditions, ink handling and sterilizer testing to gloves, plastic coverings and waste disposal.
The move is long overdue in the county, said Dominik Scalzo, owner of Dragons Lair Tattoo on MacArthur Boulevard in Oakland.
"Finally," Scalzo said. "These rules should have always been in place."
Scalzo said he was amazed at the lack of local authority oversight for tattoo shops when he came to Alameda County in 1995. He said he went to the sheriff's, police and health departments to register before he was told he didn't need to do anything.
"I was like, 'Are you kidding me?'" said Scalzo, who has been a body artist for 31 years. "You have no regulations in place for a shop that's using needles, but you'll close a restaurant down if it has a bug on the floor?"
If the ordinance is approved, it would affect body art and piercing shops only in unincorporated Alameda County, although Bill Pitcher, the county's chief of environmental protection, said the department plans to hold public meetings with city officials in the county to try to get cities to adopt the ordinance as well.
Alameda County counts 64 body art and piercing establishments and 85 registered artists.
Pitcher plans to have county counsel review a draft of the ordinance soon, then hold public meetings in the county to get more input on the proposal. The ordinance would then go before the board of supervisors, likely sometime early next year.
Reach Chris Metinko at 510-763-5418 or cmetinko@bayareanewsgroup.com.
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Breast Cancer Patients With Hepatitis C Require Surveillance to Avoid Poor Outcomes: Presented at ASCO-Breast Cancer
http://www.docguide.com
By Jerry Ingram
SAN FRANCISCO, CA -- September 11, 2007 -- Breast cancer patients who are also infected with hepatitis C virus (HCV) may require more diligent surveillance by their attending physicians, according to information presented here at the 2007 Breast Cancer Symposium, sponsored by American Society of Clinical Oncology (ASCO).
The researchers indicated in his presentation that poor outcomes in terms of viral reactivation, premature termination of chemotherapy, and delay in treatment schedules pose a significant risk for this group of patients.
In spite of the nearly four million diagnoses of HCV in the United States each year, little if anything is known about the interaction between hepatitis C and breast cancer.
"How does this study make a difference to us as doctors? [HCV] reduces our potential [breast cancer] cure rate, obviously and reduces the likelihood that we're going to have a response in the neoadjuvant setting," stated one of the study's authors P. K. Morrow, MD, Assistant Professor, Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States.
"I think what we need to do is to cooperate with hepatologists to see if we can act at the onset and see if we can reduce the type of risks that we're seeing in these patients' therapy." Morrow added.
For this investigation, Dr. Morrow and her associates collected data from the M. D. Anderson Cancer Center Tumour Registry and the Department of Laboratory Medicine at M. D. Anderson on patients with HVC and breast cancer.
The team analysed data on 43 patients, evaluating demographics, tumour characteristics, treatment course, growth factor use, complications, response to therapy, and HCV treatment.
They found that 36% of patients treated with neoadjuvant chemotherapy experienced a partial response, 36% showed no response, 18% had undocumented responses and 10% had pathological complete responses at the time of surgery.
Additionally, 70% of 20 patients who received both anthracycline and taxane therapy experienced grade 3 or greater complication, the most common being neuropathy and neutropenic fever/infection.
Thirty percent of the ten patients who received anthracycline-based chemotherapy (without taxanes) developed grade 3 or greater complications, they reported. Finally, they found that all three of the women treated with taxane monotherapy developed grade 3 toxicity.
While Dr. Morrow pointed out the limitations of this study in terms of it's size and retrospective nature, she suggested the need for a larger study. "Ideally, we should go back and compare these rates with rates of control patients," she added.
[Presentation title: Effects of Hepatitis C on the Treatment of Breast Cancer. Abstract 189]
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Anadys Pharmaceuticals Presents Preclinical Results on ANA598, a Non-Nucleoside Inhibitor of the NS5B Polymerase, at the 14th International Symposium on Hepatitis C Virus and Related Viruses
http://money.cnn.com
ANA598 demonstrates favorable preclinical antiviral, metabolic, pharmacokinetic and preliminary toxicologic properties
SAN DIEGO, Sept. 11 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. presented preclinical data today on ANA598, a non-nucleoside inhibitor of the HCV NS5B polymerase, during a poster session at the 14th International Symposium on Hepatitis C Virus and Related Viruses.
The report characterized the favorable antiviral, metabolic, pharmacokinetic and preliminary toxicologic properties that supported the decision announced in June to progress ANA598 to IND enabling studies and subsequent clinical evaluation expected to commence in the first half of 2008. ANA598 is a potent, low-nanomolar inhibitor of HCV genotype 1a and 1b replicons and has exhibited good metabolic stability properties in in vitro preclinical studies. It also does not significantly inhibit or induce cytochrome enzymes, indicating that the compound has a low likelihood of producing clinical drug-drug interactions. ANA598 was well tolerated in 14-day dose range finding (DRF) animal toxicology studies at all doses tested (1 to 1000mg/kg). In in vivo preclinical studies designed to be predictive of potential human doses, trough plasma concentrations of ANA598 24 hours post dosing exceeded the EC95 for HCV genotype 1a and 1b replicon inhibition at doses corresponding to estimated human doses. The EC95 is the concentration required to suppress hepatitis C viral RNA levels by 95% in the replicon assay.
"We are pleased with the ANA598 plasma exposures we have observed in animal studies at doses that were well tolerated for 14 days," said Steve Worland, Ph.D., President and Chief Executive Officer of Anadys. "In chronic viral diseases, achieving blood levels in preclinical studies that are many-fold above concentrations needed for viral suppression is generally recognized as a predictor of potential clinical utility."
In June, Anadys announced the nomination of ANA598 as a clinical development candidate. ANA598 was selected from the Company's internal NS5B discovery efforts based on an optimized balance of preclinical properties and was the result of the Company's structure-based drug design capabilities. ANA598 is undergoing IND enabling activities and an IND submission is targeted for the first half of 2008.
"After completing the necessary IND enabling studies, we look forward to exploring the potential clinical utility of ANA598 in patients with HCV," said James Freddo, MD, Anadys' Chief Medical Officer. "Based on the combined potency, pharmacokinetic and preliminary toxicologic properties of ANA598, we believe that this is an exciting new direct antiviral to investigate for the treatment of patients with hepatitis C virus infection."
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company committed to advancing patient care by developing and commercializing novel small molecule medicines for the treatment of hepatitis C virus (HCV) infection and cancer. The Company is developing ANA598, a small-molecule, non-nucleoside inhibitor of the NS5B polymerase for the treatment of HCV and ANA773, an oral TLR7 agonist prodrug for cancer.
SafeHarbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to the expected timing and planned development activities for ANA598, the prediction that ANA598 has a low likelihood of producing clinical drug-drug interactions, the use of doses in preclinical studies that are designed to be predictive of human doses, the belief that achieving blood levels that are many-fold above plasma levels needed for viral suppression is generally recognized as a predictor of potential clinical utility, and the belief that ANA598 is an exciting new direct antiviral to investigate for the treatment of patients with HCV infection.. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical studies may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by risks related to its agreements with Novartis and LG Life Sciences, competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments involving future products and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2006 and Anadys' Form 10-Q for the quarter ended June 30, 2007. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
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September 13th, 2007
N&N makes cancer breakthrough
http://www.eveningnews24.co.uk/
SARAH HALL
Thousands of cancer patients from across the world are set to benefit from pioneering new treatment being developed at the county's flagship hospital.
Consultants at the Norfolk and Norwich University Hospital have developed an innovative treatment which “cooks” tumours on the liver to ensure all cancerous tissues are destroyed and minimise the chances of the disease reoccurring.
The treatment has been piloted in laboratories and is set to be practiced on patients by this time next year - and the benefits will be experienced across the globe.
In particular many patients with cirrhosis or the fatal blood disease hepatitis C, both common causes of liver tumours, could see a massive improvement in the way the diseases are treated.
With a Hepatitis C “epidemic” on the horizon the development could have not have come at a better time according to the two people responsible for the treatment, Dr John Cockburn and Mr Simon Wemyss-Holden.
Mr Wemyss-Holden, a consultant in hepatobiliary and laparascopic liver surgery and also the hospital's cancer lead clinician, explained: “A number of “ablative” techniques have been used for years to treat tumours on the liver,” he said.
“It means the cancers are burnt off but none of them are perfect and on many occasions some tissue cells are left behind or the tumour can grow back after being burnt away.
“Our technique means about three times the amount of tumour or surrounding tissue is destroyed which increases the chances of a patient recovering.
“We do not know exactly how many patients will benefit but there is a rise in liver cirrhosis locally because of alcoholism and a rise in cirrhosis globally because of hep C, in fact we are nearing an epidemic.
“So potentially thousands of patients locally, nationally and internationally will see the significance of this treatment.”
The practice uses the development of a current practice called radio frequency ablation with a new electric tissue ablation which keeps the needle or probe used for treatment hydrated with water which means more tissue is destroyed and the chances of the tumour coming back is reduced.
The two medical professionals have been researching the new technique for about two years and have been working with their counterparts at the Queen Elizabeth Hospital in Adelaide, Australia to practice the methods on laboratory livers.
As well as treating patients with primary liver tumours, or hepatomas, the ablative treatment will also prove essential is dealing with secondary tumours which form on the liver following colon or bowel cancer.
In Norfolk there has been an increase in the number of people with hepatitis C with almost 2,000 people living with the disease in Norwich alone. Across the world tens of thousands of people are living with the disease and many are not even aware of it.
Dr Cockburn, lead consultant in angio-interventional radiology at the N&N, said: “We know this technique works and we know it kills far more of the tumour and surrounding tissues than other techniques.
“We are just fine-tuning the whole process now to enable us to start practicing it on patients and it is important to remember it is only applicable to certain types of tumours.
“Without this keyhole surgery some of the tumours would be inoperable and that is extremely significant.
“This sort of development is very important because it shows what we can do as a teaching hospital. While treating local patients we have also had the opportunity to develop a treatment which can benefit people from all over the world.”
The duo have already presented the treatment in Australia, Italy and parts of the UK and said it has been very well received.
In 2005 they won the education award for the Royal College of Radiologists for their invention and early this year were rewarded with an ongoing bursary from Health Enterprise East.
The initial funds for £13,000 were used for a machine that will create the new “burning” techniques and there will be more funding as the initiative is developed and expanded.
Ablative therapy has been permitted by the government watchdog Nice (National Institute for Clinical Excellence) so there are no concerns this development will be prevented from being used on the NHS.
This development joins a list of pioneering techniques deriving from the county's boffins in the past year.
Scientists from the Institute of Food Research (IFR) have made a vital breakthrough in the battle against potentially life-threatening food allergies.
A team identified a molecule that could protect against allergies to foods such as nuts, fish and milk, which are becoming increasingly common.
Norwich scientists could also hold the key to a breakthrough in the battle against hospital superbugs with experts at the John Innes Centre behind a drive to find ways of killing bugs such as MRSA and Clostridium difficile (C diff).
Do you know of any major breakthroughs in science or medical research? Is your company involved in innovative research? Do you have a health story for the Evening News? Call Sarah Hall on 01603 772426 or email sarah.hall2@archant.co.uk
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New hepatitis C virus findings from the United States and Italy detailed
http://www.therapeuticsdaily.com/
Studies from the United States and Italy have provided new information about hepatitis C virus.
Study 1: Scientists discuss in "Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress" new findings in hepatitis C virus. "Hepatic steatosis is a common histological feature of chronic hepatitis C. Hepatitis C virus (HCV) gene expression has been shown to alter host cell cholesterol/lipid metabolism and thus induce hepatic steatosis," researchers in the United States report.
"Since sterol regulatory element binding proteins (SREBPs) are major regulators of lipid metabolism, we sought to determine whether genotype 2a-based HCV infection induces the expression and posttranslational activation of SREBPs. HCV infection stimulates the expression of genes related to lipogenesis. HCV induces the proteolytic cleavage of SREBPs. HCV core and NS4b derived from genotype 3a are also individually capable of inducing the proteolytic processing of SREBPs. Further, we demonstrate that HCV stimulates the phosphorylation of SREBPs. Our studies show that HCV-induced oxidative stress and subsequent activation of the phosphatidylinositol 3-kinase (PI3-K)-Akt pathway and inactivation (phosphorylation) of PTEN (phosphatase and tensin homologue) mediate the transactivation of SREBPs. HCV-induced SREBP-1 and -2 activities were sensitive to antioxidant (pyrrolidine dithiocarbamate), Ca(2+) chelator 1,2-bis(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra(acetoxymethyl) ester (BAPTA-AM), and PI3-K inhibitor (LY294002)," wrote G. Waris and colleagues, University of California, Division of Infectious Diseases.
The researchers concluded: "Collectively, these studies provide insight into the mechanisms of hepatic steatosis associated with HCV infection."
Waris and colleagues published their study in the Journal of Virology (Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress. Journal of Virology, 2007;81(15):8122-30).
For additional information, contact G. Waris, University of California, University of California, Division of Infectious Diseases, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 USA..
Study 2: According to a study from the United States, hepatocyte nuclear factor (HNF) 1 and hepatocyte nuclear factor (HNF) 4 mediate hepatic multidrug resistance protein (MRP) 2 up-regulation during hepatitis C virus (HCV) gene expression.
"HCV is known to induce hepatic oxidative stress that is implicated in the up-regulation of MRPs. The relationship between increased prooxidant production, MRPs, and HCV has not been investigated.
"Here, we report that a homeodomain-containing transcription factor, HNF 1, plays a central role in liver gene regulation during HCV gene expression and/or subgenome replication," wrote I. Qadri and colleagues, University of Colorado.
"MRP2 protein and mRNA expression were increased and MRP2 promoter activity was increased 7-fold. Mutations within the putative HNF1 binding site of the human MRP2 promoter abrogated HCV-induced activation, implicating HNF1 in the induction of MRP2 by HCV. The mechanism by which HNF1-mediated activation occurs seems to be transcriptional, because the regulated expression of HNF4, which is known to control HNF1 expression, was also increased. Consistent with this finding, HNF1 mRNA was increased 10-fold.
"A promoter-luciferase construct of the human HNF1 gene was activated in an HNF4-dependent manner, and a mutant construct lacking the HNF4 binding site was not activated in HCV-positive cells. Consistent with this hypothesis, HNF4 protein and mRNA levels as well as HNF4 promoter activity and DNA binding activity were increased," the investigators reported.
The authors concluded, "The expression of HNF1 seems to play a critical role in the induction of hepatic MRP2 secondary to HCV subgenomic replication. The ability of HCV to induce HNF1 and HNF4 is attributed to 1) increased oxidative stress and 2) direct protein-protein interactions between HCV nonstructural component (NS) 5A and HNF1, leading to enhanced HNF1 DNA binding."
The researchers further noted, "We describe a novel mechanism by which HCV gene expression may induce adaptive responses involving MRP2 via HNF1 activation. This may constitute, in part, the cellular detoxification task force during HCV infection."
Qadri and colleagues published the results of their research in Molecular Pharmacology (Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol Pharmacol, 2006;70(2):627-636).
For additional information, contact I. Qadri, University of Colorado, Health Science Center, Department of Pediatrics, Mail Stop 8106, 12801 E 17th Avenue, L-18-7403, RC-1 S, Aurora, CO 80045, USA.
Study 3: According to a study from Italy, oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-signal transducer and activator of transcription (STAT) pathway.
"Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha," wrote D. Dibona and colleagues, Consiglio Nazionale delle Ricerche (CNR).
"We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway.
"Pretreatment of Huh-7 cells with 0.5-1 MM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. The reduced expression of these genes was associated to H2O2-mediated suppression of the IFN-alpha-induced assembly of STAT factors to specific promoter motifs on IFN-alpha-inducible genes," the authors reported.
"This was accomplished by preventing the IFN-alpha-induced Tyr phosphorylation of STAT-1 and STAT-2 through the inactivation of the upstream receptor associated Tyr kinases, JAK-1 and Tyk-2. The suppression was fast, occurring within 5 mins of pretreatment with H2O2, and did not require protein synthesis," the scientists observed.
The researchers concluded, "Oxidative stress impairs IFN-alpha signaling and might cause resistance to the antiviral action of IFN-alpha in chronically HCV infected patients with high level of oxidative stress in the liver."
Dibona and colleagues published the results of their research in the Journal of Hepatology (Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway. J Hepatol, 2006;45(2):271-279).
For additional information, contact D. Dibona, Consiglio Nazionale delle Ricerche (CNR), Ist Biomedical & Immunology Molecular, Via U La Malfa, 153, I-90146 Palermo, Italy.
Pharma Business Week - Sep. 17, 2007
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Roche Launches Another Large Study With PEGASYS Plus COPEGUS
http://www.presseportal.de
- PROPHESYS Will Identify Factors That Influence Early Response to Treatment
Roche announces the start of a large multinational observational study, called PROPHESYS, in patients with hepatitis C (HCV). This international cohort study will evaluate the important factors that give hepatitis C patients the best chance of treatment success with PEGASYS(R) (peginterferon alfa-2a (40 KD)) plus COPEGUS(R) (ribavirin). PROPHESYS (PROspective observational study on Predictors of early on-treatment response on sustained virological response in a coHort of trEatment naïve HCV patientS treated with pegYlated interferonS) is the largest study of its kind and will identify factors that influence a patient's response to treatment.
It is well known that patients who respond early to treatment are more likely to achieve a sustained virological response (SVR or cure) and have less chance of relapse.
"For patients with hepatitis C, early response to treatment leads to the best chance of a cure. The PROPHESYS study will establish what factors help a patient to respond early and will give doctors a better understanding of treatment success," said Mario Rizzetto, Professor of Gastroenterology at the University of Torino, Italy, and lead investigator of the study. "Large studies, such as PROPHESYS, can define real-world clinical practice for hepatitis C."
PROPHESYS - Examining How Early Response to Treatment Influences Overall Success
Over 5,000 patients with HCV will be treated with PEGASYS plus COPEGUS in this large international observational study. Patients will be monitored during treatment and for a further 24 weeks after the end of treatment using Roche's highly sensitive COBAS(R) TaqMan(R) real-time PCR tests to measure the amount of virus in the patient's blood. Viral load levels will be recorded prior to treatment, during treatment and at the end of treatment, as well as at 12 and 24 weeks after treatment.
The study will examine whether it is possible to predict if a patient will achieve a cure based on his or her response to treatment at weeks 2, 4 or 12. The study will also examine how certain factors can influence a patient's chance for an early response, sustained virological response (SVR or cure) and relapse. Factors being evaluated include:
- Age
- Pre-treatment viral load
- Alanine aminotransferase (ALT)
- Liver fibrosis stage
- Metabolic parameters
- Race
- Weight
- Gender
Five hundred centres within 18 countries will participate in the study. Enrolment is ongoing and the study is expected to conclude in 2010.
"Roche recognises that there is a need to examine how on-treatment response can influence the overall success for people with HCV, which is why we are launching PROPHESYS," said Claire Steers, PEGASYS Lifecycle Leader at Roche in Basel, Switzerland. "This ongoing research underscores Roche's long-term commitment to curing more people of hepatitis C."
About Hepatitis C
Hepatitis C, the most common chronic blood-borne infection, is transmitted primarily through blood or blood products. Hepatitis C chronically infects 180 million people worldwide, which makes it over four times more prevalent than HIV.(1),(2) It is a leading cause of cirrhosis, liver cancer and liver failure, despite the fact that many patients can be cured.
Efficacy of PEGASYS plus COPEGUS Combination Therapy
PEGASYS plus COPEGUS is the only pegylated interferon combination therapy to have demonstrated significantly superior benefits over conventional interferon combination therapy across all HCV genotypes, irrespective of viral load.(3),(4),(5) The combination of PEGASYS plus COPEGUS consistently shows high cure rates - up to 66% overall sustained virological response - across a number of large, randomised clinical studies including in patients with difficult-to-cure disease such as genotype 1 HCV, cirrhosis and HIV-HCV co-infection.(3),(4-8)
About Roche COBAS(R) TaqMan(R) Tests
For more than a decade, Roche Diagnostics has been the world leader in providing molecular diagnostic tests for Hepatitis C, Hepatitis B, HIV, cytomegalovirus (CMV), and other infectious diseases, and was the first to develop and commercialise real-time PCR, the new gold standard in molecular testing. Roche's broad portfolio of virology tests are designed to improve disease management through diagnosis of active infections, quantification of the amount of virus in the blood (viral-load monitoring) and identification of treatment failure and disease recurrence. With a focus on helping to improve answers for doctors and patients and efficiency for labs, in 2005 Roche introduced the fully automated COBAS(R) AmpliPrep/COBAS TaqMan(R) platform, the first system to fully automate real-time PCR testing. It provides labs with flexible configurations, true walk-away capabilities and improved test-result integrity.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. Additional information is available on the Internet at http://www.roche.com.
All trademarks used or mentioned in this release are protected by law.
Film footage is available for broadcast journalists from The NewsMarket at http://www.thenewsmarket.com
References:
(1). Initiative for Vaccine Research, Viral Cancers, Hepatitis C. World Health Organization, 2006. (Accessed July 24, 2006, at http://www.who.int/vaccine_research/diseases
/viral_cancers/en/index2.html.)
(2). AIDS Epidemic Update. 2006. (Accessed February 27, 2007, at http://www.who.int/hiv/mediacentre/2006_Ep
iUpdate_en.pdf.)
(3). Hadziyannis SJ, Sette H, Jr., Morgan TR, et al. Peginterferon- alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140(5):346-55.
(4). Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004;351(5):438-50.
(5). 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(13):975-82.
(6). Marcellin P, Brillanti S, Cheinquer H. Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) is an efficacious and safe treatment for chronic hepatitis C (CHC) in patients with compensated cirrhosis. In: 38th Annual Meeting of the European Association for the Study of the Liver (EASL) July 3-6; 2003; Geneva, Switzerland; 2003.
(7). Heathcote EJ, Shiffman ML, Cooksley WG, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000;343(23):1673-80.
(8). Zeuzem S, Pawlotsky JM, Lukasiewicz E, et al. International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C. J Hepatol 2005;43(2):250-57.
ots Originaltext: Roche Pharmaceuticals
Im Internet recherchierbar: http://www.presseportal.de
Contact:
Contact: Janet Kettels, Roche, +1-862-596-9084, or Natalie Henson,
Axon Communications, +44-(0)20-843-99-406
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