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Week Ending: December 24 th, 2005
Alan Franciscus
Editor-in-Chief
To download pdf version click here
This Issue:
• Differentiation Grade Predicts Liver Transplant Survival
• Diabetes Link to Liver Disease
• Valopicitabine Showing Continued Good Results in Hepatitis C: Presented at HEP DART
• Hepatitis C Sufferers in Appeals Limbo
• Can Vitamin C Supplements Help?
• Anger Over ‘Low-Key’ Liver Report
• Clinical Trial: A Phase IIb Clinical Trial to Evaluate the Combination of Pegylated Interferon Alfa plus Valopicitabine (NM283) in Treatment-Naive Patients with Chronic Hepatitis C [NV-08A-006]
• Schering-Plough Announces Peg-Intron® And Rebetol® Approved in Japan for Expanded Use in Treating Chronic Hepatitis C
• Coffee and Tea Intake May Lower Chronic Liver Disease Risk
• Sirna Therapeutics Selects Development Candidate for Its Hepatitis C Antiviral Program
• Anadys Pharmaceuticals to Initiate 28-Day Clinical Trial of ANA975 in Patients with Chronic Hepatitis C
• Promising Test Results for Cubist's Proposed Hepatitis Treatment
• Saliva-Based Hepatitis C Test Developed
• Physicians Collecting Data on Drug at Prison
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December 19th, 2005
Differentiation Grade Predicts Liver Transplant Survival
SourceURL:http://www.gastrohep.com
Histological grade of differentiation and macroscopic vascular invasion are strong predictors of survival in patients with cirrhosis who received transplants for hepatocellular carcinoma, finds December's American Journal of Gastroenterology.
Dr Claudio Zavaglia and colleagues from Italy identified predictors of survival and tumor-free survival with orthotopic liver transplantation.
The research team assessed of a cohort of 155 patients, with hepatocellular carcinoma and cirrhosis, who were treated by orthotopic liver transplantation.
The team reported 603 orthotopic liver transplantations were performed in 549 patients from 1989 to 2002.
Hepatocellular carcinoma was diagnosed in 116 patients before orthotopic liver transplantation and in 39 at histological examination of the explanted livers.
The team reported that 84% of the patients met 'Milan' criteria at histology, and 94 patients received anticancer therapies preoperatively.
The median follow-up was 49 months.
Overall, 1-, 3-, 5-, and 10-yr survival were 84%, 75%, 72%, and 62%, respectively.
The researchers found that survival was not affected by the patient's age or sex, or etiology of liver disease.
5-year patient survival with poorly differentiated hepatocellular carcinoma was 44% – American Journal of Gastroenterology
Child score at transplantation, rejection episodes, tumor number, total tumor burden, or bilobar tumor did also not affect survival.
In addition, the team observed that survival was not affected by pathologic Tumor, Nodes, Metastasis stages.
There was no significant difference in survival when patients were grouped according to the recently proposed simplified Tumor, Nodes, Metastasis staging.
The team noted no difference in survival with grouping patients according to the United Network for Organ Sharing staging system for hepatocellular carcinoma.
The researchers observed that encapsulation of the tumor and alfa-fetoprotein levels significantly affected patient survival.
The 5-year patient survival with poorly differentiated hepatocellular carcinoma was 44%.
The team found that patients with moderately or well-differentiated hepatocellular carcinoma had 5-year survival rates of 67% and 97%, respectively.
The 5-year survival of patients with micro- or macro-vascular invasion was 49% vs 77% for patients without vascular invasion.
Multivariate analysis showed that histological grade of differentiation and macroscopic vascular invasion are independent predictors of survival.
Dr Zavaglia's team commented, "Histological grade of differentiation and macroscopic vascular invasion, as assessed on the explanted livers, are strong predictors of both survival and tumor recurrence in patients with cirrhosis who received transplants for hepatocellular carcinoma."
Am J Gastroenterol 2005: 100(12): 2708
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Diabetes Link to Liver Disease
SourceURL:http://abcnews.go.com
Karen Barrow
Most patients with diabetes know that they have an increased risk of heart disease and stroke, but few realize that their diabetes is also raising their risk of having both liver disease and liver cancer.
"There is now growing evidence that some endocrine disorders, in particular diabetes mellitus, may actually cause liver disease," said Dr. Adrian M. DiBisceglie of the division of gastroenterology and hepatology at the Saint Louis University School of Medicine in a response to the new data.
A pair of studies reveal that patients with type 2 diabetes have two times the risk of developing liver disease and possibly three times the risk of developing liver cancer as their healthy peers.
Because liver disease can go undetected for years, these findings emphasize the importance for those with diabetes to keep a close eye on their liver health.
Reviewing the Problem
In the first study, published in Gastroenterology, researchers followed over 170,000 patients with type 2 diabetes and over 650,000 patients without diabetes who were admitted to various VA hospitals across the country. Fifteen years after being discharged, the patients with diabetes were almost twice as likely to have chronic liver disease as the patients without diabetes.
While it is unclear whether diabetes directly causes liver disease, or if changes in liver function cause diabetes, Dr. Hashem El-Serag, study author from the Houston Veteran Affairs Medical Center, sees this study as an important warning for patients with diabetes. Because liver disease can often go unnoticed, as it causes no discernible symptoms, he recommends "regular testing of liver enzymes for patients with diabetes."
In a related study, published in the journal Gut, 2,061 patients with liver cancer were compared to over 6,000 patients without liver cancer from a Medicare database. The researchers found that 43 percent of the patients with liver cancer also had diabetes, while only 19 percent of the cancer-free control group had diabetes.
When other factors that contribute to liver cancer risk, like alcoholism, were taken into account, the researchers found that patients with diabetes had three times the risk of developing liver cancer as the general population.
"Our results indicate that diabetes is associated with an increased risk of [liver cancer] among people 65 years and older," wrote El-Serag.
Chronic liver diseases, caused by hepatitis B, hepatitis C, heavy alcohol consumption and fatty liver disease have previously been shown to be major risk factors for developing liver cancer, but this is the first time that diabetes alone was seen as a risk factor for liver cancer. This correlation may explain why rates of liver cancer have been on the rise in the United States.
"The incidence of liver cancer is rising in the developed Western world at a time when obesity is also emerging as a major public health threat," said DiBisceglie. "What is the link between these two phenomena?"
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Valopicitabine Showing Continued Good Results in Hepatitis C: Presented at HEP DART
SourceURL:http://www.docguide.com
By Bonnie Darves
KOHALA COAST, HI -- December 19, 2005 -- The novel prodrug valopicitabine (NM283) continues to show promise in the treatment of hepatitis C in patients who have been refractory to standard HCV therapy, according to partial 24-week results from an ongoing phase 2b trial.
Results from the trial show early virologic response (EVR) in up to 70% of patients who are taking high doses -- 400 to 800 mg daily -- of valopicitabine compared to 41% of controls on pegylated-interferon/ribavirin (peg-IFN/RBV) regimens, researchers reported here at the Frontiers in Drug Development for Viral Hepatitis HEP DART 2005 meeting.
"We are seeing statistically superior antiviral effect [with valopicitabine], and overall safety has been satisfactory to date," said Christopher O'Brien, MD, Clinical Associate Professor of Medicine, University of Miami, Miami, Florida, in a presentation on December 13th. "There have been no viral breakthroughs to date."
The "very encouraging early data" prompted Dr. O'Brien and colleagues to extend the trial to 48 weeks.
The multicenter trial, which includes 178 patients, is interesting in several regards, Dr. O'Brien said. Stringent inclusion criteria require that participants be non-responders who have failed previous treatment "for efficacy, not for tolerability," he noted.
For inclusion in the study, participants must have received at least 12 weeks of peg-IFN/ribavirin and at least 75% of the prescribed dose of both drugs. To remain in the current trial, patients also must meet mandatory response criteria at weeks 4, 12 and 24, a HCV RNA 0.5 log drop (1 IU/mL) by week 4, a 1.0 drop by week 12 and a 2.0 log drop by 24 weeks.
"If patients did not meet the response criteria they were discontinued from the trial," Dr. O'Brien said.
Patients were randomised 1:2:2:2:2, to receive valopicitabine alone, valopicitabine plus peg-IFN (400 mg, 400-800 ramping dose and 800 mg) or peg-IFN plus ribavirin in the re-treatment control group.
Dr. O'Brien explained that the study population is unusual in that it includes a large number of Asians, Middle Easterners and Indians.
The best results, as measured by HCV RNA levels, were seen in the two high-dose valopicitabine groups, who achieved -3.8 and -3.5 log10 copies/mL decreases, compared to 3 to 0.5 in the control arm.
"We find these numbers encouraging because the drops appear to be continuing down from week 12 to 24," Dr. O'Brien said.
"The consistency of response seen in the individual patient data in the valopicitabine combination arms compared to the control arm suggests that the differential in viral load reductions may continue to widen in favor of the valopicitabine combination arms as treatment progresses," he added.
Four percent of participants discontinued treatment for serious adverse events and there were no hematologic toxicities for valopicitabine monotherapy. Neutropenia and thrombocytopenia, as expected, occurred in all arms on peg-IFN, Dr. O'Brien said.
Transient nausea and vomiting were common in patients on high doses of the study drug but not severe enough to warrant discontinuation, he said.
[Presentation title: Progress with the Clinical Development of Valopicitabine (NM283) in Combination with Peg-Interferon for the Treatment of Chronic Hepatitis C, in Treatment-Naïve Patients and in Non-Responders to Peg-Interferon/Ribavirin. Abstract 21]
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Hepatitis C Sufferers in Appeals Limbo
SourceURL:http://www.redorbit.com/
By Judith Duffy Health Correspondent
HUNDREDS of hepatitis C sufferers infected by contaminated NHS blood have been left in limbo after compensation claims were refused and an appeals system failed to get off the ground.
The UK-wide Skipton Fund, which awards ex-gratia payments of up to pounds-45,000, began processing claims in July of last year, providing assistance for haemophiliacs who had contracted the deadly liver disease through transfusions in the 1970s and 1980s.
Since then, 316 applicants out of 3640 across the UK have had their claims rejected. But they have been left unable to challenge the decision because the promised appeals tribunal has yet to be established.
SNP health spokeswoman Shona Robison MSP, who raised the issue in a parliamentary question, said there was "no excuse" for any further delay. "For many people time isn't on their side and delays like this in the decision-making isn't acceptable, " she said.
Health minister Andy Kerr said Westminster had been developing procedures in consultation with the devolved administrations and added that he regretted the delay.
Philip Dolan, chairman of the Scottish Haemophilia Groups Forum, called for the Executive to establish a tribunal to deal with Scottish appeals.
Source: Sunday Herald
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Can Vitamin C Supplements Help?
http://www.americanchronicle.com
By Daniel Weigum
The cold and flu season usually drags a percentage of the population down at some time during the year. A clinic visit and some prescription drugs is the usual method of dealing with out of control cold and flu symptoms. Is cold and flu prevention possible?
Vitamin C has gained a reputation of strengthening the immune system. Is this possible? A simple vitamin supplement can offer immunity to some of the most common illnesses afflicting the public today. Studies have indicated vitamin C really can help.
The American Academy of Allergy, Asthma, and Immunology recently conducted a study on the affects of vitamin C on the immune system. Susan Ritter, MD, PhD candidate, and Gailen D. Marshall, Jr., MD, PhD, both from the University of Texas Health Science Center, studied the blood of 12 anonymous patients given a one gram daily vitamin C supplement.
An increase in NK cells was found in all patients after the 2 week vitamin C supplement trial. The NK cells are important in immunity against viral infections. NK cells (Natural Killer cells) are large, granular lymphocytes carried in the blood. The NK cells function basically as a soldier waiting for a mission. When infection activates an immune system response, NK cell are signaled and initiate an attack destroying pathogens as they are designed. The increase level of Natural Killer cells in vitamin C supplement test subjects suggests an increased immunity to infections.
Vitamin C supplement subjects also had an increased level of interferon-gamma. Interferon-gamma is used by the cytotoxic T cells to do a couple of important functions. During a viral infection, cytotoxic T cells are formed specifically to attack the virus infecting the body. When the cytotoxic T cell targets an infected tissue cell, interferon-gamma is secreted and used to prevent the infected cell from replicating into another viral pathogen, increases the processing and presentation of viral infections with MHC class I molecules, and activates macrophages in the area of the infection near the cytotoxic T cell.
The three important steps referred to above can be simplified into isolation, assassination, and finally elimination. The cell replication is stopped when the cytotoxic T cell introduces interferon-gamma. The cell is programmed to die with use of MHC class I molecules. Finally, the dead interferon-gamma coated cell is easily identified as a foreign body and eliminated by the macrophages. Interferon-gamma triggers all three of these events which makes the immune system much more efficient when engaging in battle with a viral infection. The cytotoxic T cell can effectively kill several infected tissue cells from one to the next as well as gain space to maneuver as dead infected cells are eliminated by the macrophages.
A reduction of the presence of interleukin-4 and interleukin-10 were also found in the vitamin C supplement test subjects. Interleukin is secreted by T cells to initiate naive B cells to differentiate into plasma cells secreting immunoglobulins. This antibody response occurs during infections. Interleukins trigger or inhibit the different types of immunoglobulin formation. Immunoglobulin can be tailored to respond to different types of infections. The reduced levels of interleukin-4 and interleuking-10 give evidence of the decreased need of an antibody response by the immune system. The immune system function efficiency is more effective requiring less need for distinct antibody production.
Vitamin C supplements have had a profound affect on this group of people as well as survived the old home remedy tests passed down from generations before. Today, the glass of orange juice isn't the only vitamin C source available. Simple measures such as benefiting the body with vitamin C can keep the body healthy. Instead of reaching for a Kleenex, the offer of a Kleenex to a sick coworker might be a better way to live through the cold and flu season.
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December 20th, 2005
Anger Over 'Low-Key' Liver Report
SourceURL:http://services.press.net
By Ben Pindar, Community Newswire
A charity dedicated to supporting people with liver disease has today hit out over a "low-key" and "non-urgent" Health Protection Agency (HPA) report on hepatitis C.
The British Liver Trust today described its disappointment at the report and claimed it reflected the Government's overall approach to liver disease.
Chief executive of the charity, Alison Rogers, said: "The true burden of both hepatitis C and hepatitis B in terms of future health care and the inevitable impact on society as a whole, appears to be falteringly recognised but is falling on deaf ears."
The report estimates there are currently 4,500 people in the UK living with severe liver disease as a result of having a chronic hepatitis C infection and forecasts that the figure could rise to around 7,000 with severe liver disease by 2010.
However, HPA hepatitis C expert Dr Helen Harris says a large proportion of the 200,000 individuals with chronic hepatitis C in the country will go on to develop severe liver damage over the coming years.
"The Trust is very concerned that much of the epidemiology in the report is out of date," said Ms Rogers. "It certainly does not reflect the experience of liver specialists or convey the magnitude of the problem, diluting the impact and urgency this report should have had.
"We find it shocking that the HPA is only able to quote prevalence figures based on 1995/96 information and no better efforts have been made to achieve reliable estimates, despite the fact that we have known about hepatitis C for more than 20 years.
"Almost 6,000 new cases are diagnosed each year and we believe there are many thousands more who remain undiagnosed and could be cured with available treatment.
"There is wider recognition of consistently higher levels of liver disease reported by medical professionals yet there continues to be glaring contradictions in Government policy.
"The relaxation of the licensing laws despite the increasing numbers of people with alcoholic liver disease is a prime example."
Despite the disappointment surround the new report the British Liver Trust has welcomed the comments of Professor Pat Troop, chief executive of the HPA, who has highlighted the vital role of public and professional awareness campaigns.
Professor Troop said: "Our report shows that the burden hepatitis C places on the individual and on healthcare services is high and will rise in the future.
"Public and professional awareness campaigns will help reduce the level of undiagnosed infections and consequently the level of disease."
The trust said that despite moves to raise the profile of needle exchange services and the suggestion that there should be antenatal screening of all women for hepatitis C, the report makes little reference to any serious national campaign or real funding support.
Ms Rogers added: "Support for the general population is seriously lacking. We are aware of major liver units where funding for the treatment of people with hepatitis C has been limited to one new patient a week - and this is regarded as a success story.
"This approach, providing so little substance and glossing over the real evidence is disappointing and most frustrating for all those working with people with liver disease.
"There is a long overdue need for more public investment in fighting liver disease. A major national awareness and prevention campaign to health professionals and the public would be an effective starting point."
The British Liver Trust is Britain's only national liver disease charity for adults, existing to improve the lives of people suffering from liver disease, of which there are over 100 different forms.
For more information about the work of the charity visit the website at www.britishlivertrust.org.uk
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December 21st, 2005
Clinical Trial: A Phase IIb Clinical Trial to Evaluate the Combination of Pegylated Interferon Alfa plus Valopicitabine (NM283) in Treatment-Naive Patients with Chronic Hepatitis C [NV-08A-006]
SourceURL:http://www.centerwatch.com
This is a research study of an investigational new drug called valopicitabine (NM283) for treating chronic hepatitis C virus (HCV). The purpose of this study is to see how safe it is to take NM283 and pegylated interferon alfa together, and find out how well these drugs work together to help get rid of hepatitis C.
- Participation may last for up to 1 1/2 years which includes about 20 clinic visits.
- All study medications and procedures will be provided at no cost.
- Compensation Provided
Patient Inclusion/Exclusion Criteria:
You may be eligible to participate if you
- are 18-65 years old
- have been diagnosed with hepatitis C
- have not received treatment for your hepatitis C
- meet additional criteria
You will not be able to participate if you
- are pregnant or breastfeeding
- are infected with hepatitis B
- are HIV positive
- have used methadone or have had a substance abuse problem within the past year
Contact:
Juanita Jones, coordinator
Mount Sinai Medical Center
One Gustave L. Levy Place
New York, NY 10029
Telephone: 212-241-1617
Fax: 212-241-4465
Email: juanita.jones@mountsinai.org
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December 22nd, 2005
Schering-Plough Announces Peg-Intron® and Rebetol® Approved in Japan for Expanded Use in Treating Chronic Hepatitis C
Press Release: Schering-Plough Corporation
Combination Therapy Receives Additional Indication for Treating Patients Other Than Those with Genotype 1 Virus and High Viral Load
KENILWORTH, N.J., Dec. 22, 2005 – Schering-Plough Corporation (NYSE: SGP) today announced that Schering-Plough K.K., the company’s country operations in Japan, has received marketing approval for a new, additional indication for PEG-INTRON® (peginterferon alfa-2b) Powder for Injection in combination with REBETOL®(ribavirin) Capsules – the treatment of chronic hepatitis C in adult patients other than those with genotype 1 virus and high viral load. This expanded use represents approximately 40 percent of the patient population in Japan. With this approval, PEG-INTRON and REBETOL is indicated for the treatment of the vast majority of Japanese patients diagnosed with chronic hepatitis C virus (HCV) infection.
The approval by the Ministry of Health, Labor and Welfare (MHLW) follows a priority review designation granted May 18, 2005. An estimated 1 to 2 million Japanese are chronically infected with hepatitis C.
PEG-INTRON and REBETOL was first approved in Japan in October 2004 for treating patients with genotype 1 virus (genotype 1a or 1b) and high viral load for a recommended duration of 48 weeks. With this new, expanded approval, the recommended duration of therapy for all other HCV indications is 24 weeks. This includes patients with genotype 2 or 3 virus and high viral load, as well as patients with genotype 1, 2 or 3 virus and low viral load who did not respond or who relapsed following treatment with interferon monotherapy. In the Japanese clinical study supporting this approval, a sustained virologic response (SVR)1 rate of nearly 90 percent was achieved in these patients with 24 weeks of therapy.
“This expanded indication for PEG-INTRON and REBETOL combination therapy represents a significant advance in the treatment of chronic hepatitis C, a major public health problem in Japan,” said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute. “This approval, and the supporting clinical data, further underscore the efficacy of individualized, weight-based PEG-INTRON used in combination with REBETOL in treating chronic hepatitis C.”
PEG-INTRON and REBETOL is the only pegylated interferon-based combination therapy for hepatitis C approved in Japan. PEG-INTRON is administered once weekly in combination with REBETOL daily. Importantly, PEG-INTRON is the only peginterferon product approved in Japan for which a blood test is not required before every injection.
HCV genotype 1 is generally considered to be the most difficult-to-treat form of hepatitis C and is the most common form in Japan, accounting for approximately 70 percent of all HCV infections there.
Hepatitis C is the leading cause in Japan of liver cancer, with more than 35,000 deaths occurring annually. Hepatitis C is the most common reason for liver transplant in major world markets, including Japan, according to the World Health Organization (WHO).
In the United States, PEG-INTRON and REBETOL combination therapy is indicated for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.
Important Safety Information Regarding U.S. Labeling for PEG-INTRON and REBETOL
WARNING
Alpha interferons, including PEG-INTRON, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping PEG-INTRON therapy.
Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.
REBETOL and combination REBETOL/PEG-INTRON therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL and combination REBETOL/PEG-INTRON therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (at least two reliable forms) during treatment and during the 6-month post-treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064.
PEG-INTRON
There are no new adverse events specific to PEG-INTRON as compared to INTRON® A (interferon alfa-2b, recombinant) for Injection, however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEG-INTRON were “flu-like” symptoms, occurring in approximately 50% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2% of patients receiving PEG-INTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEG-INTRON.
Psychiatric adverse events, which include insomnia, were common (57%) with PEG-INTRON, but similar to INTRON A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEG-INTRON.
PEG-INTRON/REBETOL is contraindicated in patients with autoimmune hepatitis, decompensated liver disease, and in patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia).
The following serious or clinically significant adverse events have been reported at a frequency less than or equal to 1% with PEG-INTRON or interferon alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.
In the PEG-INTRON/REBETOL combination trial the incidence of serious adverse events was 17% in the PEG-INTRON/REBETOL groups compared to 14% in the INTRON A/REBETOL group. The incidence of severe adverse events in the PEG-INTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEG-INTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEG-INTRON (1.5 mcg/kg)/ REBETOL and in 34% of those receiving INTRON A/REBETOL.
REBETOL should not be used in patients with creatinine clearance less than 50 mL/min.
Schering-Plough K.K., based in Osaka, Japan, is the country operations of Schering-Plough Corporation, a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough’s vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company is based in Kenilworth, N.J., USA, and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including statements relating to PEG-INTRON and REBETOL and the potential market for these drugs. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough’s forward-looking statements, including market forces, economic factors, product availability, current and future branded, generic or over-the-counter competition and the regulatory process, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough’s Securities and Exchange Commission filings, including the company’s third quarter 2005 10-Q.
1 SVR is defined as the sustained undetectability of the hepatitis C virus six months following therapy.
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Coffee and Tea Intake May Lower Chronic Liver Disease Risk
SourceURL:http://www.gastrohep.com/
This month's issue of Gastroenterology finds that coffee and tea drinking decreases the risk of clinically significant chronic liver disease.
Coffee drinking has been suggested to protect against liver injury, but it is uncertain whether this is of clinical significance.
Dr Constance Ruhl and Dr James Everhart from Maryland examined the relationship of coffee and tea consumption with the incidence of hospitalization or death from chronic liver disease.
The research team assessed participants in the population-based, first National Health and Nutrition Examination Survey from 1971 to 1975.
The participants were asked about coffee and tea consumption, which was categorized as less than 1 cup, 1 to 2 cups, and more than 2 cups per day.
The risk with more than 2 cups per day was less than half the rate than with 1 cup per day – Gastroenterology
A second analysis included persons who, from 1982 to 1984, were asked more detailed questions on coffee and tea drinking.
The team reported that participants were followed through from 1992 to 1993 for a hospital or death certificate diagnosis of chronic liver disease or cirrhosis.
Hazard rate ratios for chronic liver disease according to coffee and tea intake were calculated using Cox proportional hazards analysis.
Among 9849 persons followed for a median of 19 years, the researchers found that the cumulative incidence of chronic liver disease was about 1%.
In multivariate analysis, those who drank more than 2 cups per day had less than half the rate of chronic liver disease as those who drank less than 1 cup per day.
The team noted that protection by coffee and tea was limited to persons at higher risk for liver diseases.
The higher risks for liver disease were from heavier alcohol intake, overweight, diabetes, or high iron saturation.
The team further assessed 9650 participants who provided detailed drink information in 1982 to 1984.
Among these participants, the team observed that "intake of regular ground coffee and of caffeine was associated with lower incidence of chronic liver disease."
Dr Ruhl and colleague concluded, "Coffee and tea drinking decreases the risk of clinically significant chronic liver disease."
Gastroenterol 2005: 129(6): 1928-36
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Sirna Therapeutics Selects Development Candidate for Its Hepatitis C Antiviral Program
SourceURL:http://biz.yahoo.com
Systemically Delivered siRNA Designed to Dramatically Reduce Drug Resistant Variants
SAN FRANCISCO, Dec. 21 /PRNewswire-FirstCall/ -- Sirna Therapeutics, Inc. (Nasdaq: RNAI - News), a leading RNAi therapeutics company, announced today that it has selected Sirna-AV34, a systemically delivered, chemically modified short interfering RNA (siRNA) compound, as its candidate for advancement to human clinical testing against Hepatitis C virus. Sirna completed its preclinical evaluation of the efficacy of Sirna-AV34 and has begun cGMP manufacturing for its Phase I clinical studies. Sirna expects to initiate IND-enabling toxicology studies in the first quarter of 2006 followed by the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by the fourth quarter of 2006.
Sirna-AV34 is a systemically delivered, nanoparticle-based therapeutic targeting the Hepatitis C virus. The compound consists of multiple individual, chemically modified, siRNA sequences which target highly conserved sequences in the Hepatitis C viral genome. Sirna-AV34 is designed to inhibit viral replication and dramatically reduce the selection of drug resistant mutant variants. The design principles used in Sirna-AV34 were validated by demonstrating reduction in escape mutation frequency in the Hepatitis C virus sub-genomic replicon system in vitro. No existing therapeutic approach has the potential to broadly inhibit Hepatitis C viral replication while reducing the probability of drug resistant variants.
"We are extremely pleased by the significant progress of our Hepatitis C antiviral program," stated Sirna Senior Vice President and Chief Scientific Officer, Barry Polisky, PhD. "The selection of Sirna-AV34 as our clinical candidate reflects two major accomplishments of our research team. The first is the design, chemical modification and synthesis of a stable and potent siRNA compound which is effective broadly against the Hepatitis C virus. The second is the development of a proprietary nanoparticle delivery technology capable of efficient and specific delivery of the siRNA compound to hepatocytes. These two achievements have provided us with a unique opportunity to bring this groundbreaking therapy to the clinic."
Sirna has completed its preclinical evaluation including demonstration of systemic efficacy in both rodent and non-human primate animal models. As previously reported in a rodent model of Hepatitis B virus used as a surrogate for Hepatitis C virus, Sirna demonstrated that a chemically optimized and encapsulated siRNA had significant antiviral activity and prolonged duration of effect in vivo. Recent data from a non-human primate model of Hepatitis C replication demonstrated that Sirna's systemically delivered siRNA compound dramatically suppressed Hepatitis C viral titers via an RNA interference mechanism.
"We are very excited to be moving a systemically delivered siRNA towards the clinic," stated Roberto Guerciolini, MD, Senior Vice President and Chief Medical Officer. "Since the current treatments for chronic Hepatitis C remain highly unsatisfactory, we believe that the application of an siRNA compound targeting multiple components of the viral genome will result in a significant advancement in the treatment of this disease."
Sirna-AV34 will be manufactured at Sirna's cGMP facilities in Boulder, Colorado for both Phase I enabling toxicology studies and Phase I human clinical testing.
About Sirna Therapeutics
Sirna Therapeutics is a clinical-stage biotechnology company developing RNAi-based therapies for serious diseases and conditions, including age-related macular degeneration (AMD), hepatitis B and C, dermatology, asthma, Huntington's disease, diabetes and oncology. Sirna Therapeutics has presented interim Phase 1 clinical trial data for its most advanced compound, Sirna-027, a chemically optimized siRNA targeting the clinically validated vascular endothelial growth factor pathway to treat AMD. Sirna-027, which has been partnered with Allergan, Inc., has been shown to be safe and well tolerated with a trend toward visual acuity improvement and demonstrated biological activity. Sirna has a leading intellectual property portfolio in RNAi with 45 issued patents and over 250 pending applications worldwide. More information on Sirna Therapeutics is available on the Company's web site at http://www.sirna.com.
Safe Harbor Statement
Statements in this press release which are not strictly historical are "forward-looking" statements which should be considered as subject to many risks and uncertainties. For example, Sirna's ability to develop a treatment for Hepatitis C will require additional, much more costly clinical trials, the results of which are highly uncertain. Moreover, Sirna's ability to develop products and operate as a going concern requires significant cash to fund its operating programs. Additional risks and uncertainties include Sirna's early stage of development and short operating history, Sirna's history and expectation of losses and need to raise capital, Sirna's need to obtain clinical validation and regulatory approval for products, Sirna's need to obtain and protect intellectual property, risk of third-party patent infringement claims, Sirna's need to attract and retain qualified personnel, Sirna's need to engage collaborators, availability of materials for product manufacturing, the highly competitive nature of the pharmaceutical market, the limited trading volume and history of volatility of Sirna's common stock, Sirna's concentration of stock ownership, and risks from relocating Sirna headquarters. These and additional risk factors are identified in Sirna's Securities and Exchange Commission filings, including the Forms 10-K and 10-Q and in other SEC filings. Sirna undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.
Contacts:
J. Michael French
Senior Vice President, Corporate Development
Sirna Therapeutics, Inc.,
(303) 449-6500
Investors
Francesca DeMartino
The Ruth Group
(646) 536-7024
fdemartino@theruthgroup.com
Media
Jason Rando
The Ruth Group
(646) 536-7025
jrando@theruthgroup.com
Source: Sirna Therapeutics, Inc.
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Anadys Pharmaceuticals to Initiate 28-Day Clinical Trial of ANA975 in Patients with Chronic Hepatitis C
Source: www.prnewswire.com
Proof-of-Concept Trial in U.S. and E.U. to Build on the Clinical Results of Previously Completed Phase I Studies 501, 502 and 503
SAN DIEGO, Dec. 22 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it plans to initiate a Phase Ib, placebo-controlled, multiple-dose clinical trial of ANA975 in chronic hepatitis C patients in January. The trial is designed to evaluate the safety, tolerability and viral load reduction of ANA975 in hepatitis C patients. ANA975, which Anadys is developing in collaboration with Novartis, is the oral prodrug of isatoribine, a proprietary Toll-Like Receptor-7 (TLR7) agonist.
"With this study we are seeking to extend the encouraging clinical results we obtained in several Phase I clinical trials -- Studies 501, 502 and 503 -- with healthy volunteers that evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of ANA975," said Kleanthis G. Xanthopoulos, Ph.D., Anadys' President and CEO. "We reported the initial part of these studies at the recent annual meeting of the American Association for the Study of Liver Diseases (AASLD) in November 2005."
"The data from ANA975 so far demonstrate the power of our unique and proprietary oral TLR-7 prodrug technology and build on the clinical experience of the active substance, isatoribine, that has demonstrated statistically significant antiviral activity in patients chronically infected with hepatitis C virus, as we have previously reported," said Steve Worland, Ph.D., Anadys' Executive Vice President, Pharmaceuticals. "We are excited to see ANA975 entering the clinic in hepatitis C patients."
ANA975 has been administered to more than 90 healthy volunteers in three completed Phase I trials (501, 502, and 503), setting the stage for the upcoming 28-day clinical study in hepatitis C infected patients. Results from several clinical trials in hepatitis C patients receiving intravenous isatoribine for one week have demonstrated statistically significant and therapeutically relevant viral load reductions. Data from the previous Phase I clinical trials of ANA975 in healthy volunteers indicate that the bioavailability of ANA975 is greater than 80 percent and conversion to isatoribine in plasma is rapid and effective, delivering levels of isatoribine that have been shown to be clinically relevant.
The trial, which will be conducted at multiple centers in the United States and the European Union, will evaluate the safety, tolerability and viral load reduction of ANA975 at multiple doses for 28 days in patients chronically infected with hepatitis C.
Patients will be assigned randomly to one of two main categories. In one category patients will receive either a predetermined dose of ANA975 once a day for 28 days or a placebo. In a second category patients will receive a predetermined dose of ANA975 twice a day for 28 days or a placebo. Anadys expects to report clinical data from this study in the first half of 2006.
Hepatitis C Virus
Hepatitis C virus causes inflammation of the liver and degradation of liver function. Approximately 80% of individuals infected with hepatitis C progress to chronic hepatitis. The most common signs and symptoms of chronic hepatitis, which may show no symptoms for many years, include an enlarged liver and spleen, jaundice, muscle wasting, excoriations (the result of scratching), ascites (swelling of the abdomen) and swelling of the ankles. Chronic infection often progresses to further, more serious complications such as cirrhosis of the liver, liver cancer and death. Of those patients who progress to chronic hepatitis, 10%-20% develop cirrhosis over a period of 20 years, with approximately 1-5% of these patients progressing to end-stage liver disease or liver cancer in their lifetime. Hepatitis C is estimated to chronically infect more than 170 million people worldwide.
The CDC reports that approximately 2.7 million Americans are chronically infected with hepatitis C and at risk of disease progression. There is no vaccine available to prevent the spread of hepatitis C.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company committed to advancing patient care by discovering, developing and commercializing novel small molecule medicines for the treatment of hepatitis, other serious infections, and cancer. The Company has core expertise in Toll-Like Receptor-based small molecule therapeutics and structure-based drug design coupled with medicinal chemistry. Anadys' clinical development programs include ANA975 for the treatment of hepatitis C and hepatitis B, and ANA380 for the treatment of hepatitis B. In addition, Anadys' therapeutic platform is designed to advance a strong and continual pipeline of drug candidates into the clinic.
Safe Harbor 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 Anadys' plan to initiate the Phase Ib trial in January, that the trial will be a proof-of-concept trial, the desire to extend the encouraging clinical results Anadys previously obtained in the previously completed Phase I clinical trials, the power of Anadys' TLR-7 technology, the planned design of the Phase Ib clinical trial, the predictive power of the results from clinical trials of isatoribine, as well as references to the extent to which ANA975 is converted to isatoribine and the corresponding oral bioavailability of ANA975. 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. In particular, the results of initial clinical trials may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will have favorable results in future clinical trials or receive regulatory approval. In addition, Anadys' results may be affected by risks related to the implementation of its collaboration with Novartis, competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, the level of effort that its collaborative partners devote to development and commercialization of its product candidates, difficulties or delays in its 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. These and other factors that may cause actual results to differ are more fully discussed in the "Risk Factors" section of Anadys' Form 10-Q for the quarter ended September 30, 2005. 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.
SOURCE Anadys Pharmaceuticals, Inc.
CONTACT: Vince Reardon, Sr. Director, Investor Relations & Corporate Communications of Anadys Pharmaceuticals, Inc., +1-858-530-3653, vreardon@anadyspharma.com
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Promising Test Results for Cubist's Proposed Hepatitis Treatment
SourceURL:http://www.bizjournals.com
Boston Business Journal
Cubist Pharmaceuticals Inc. has gotten positive midstage human clinical trial results for a therapy to prevent new hepatitis B infections in patients with liver transplants.
The Lexington, Mass.-based company (Nasdaq: CBST) said that its HepeX-B treatment helped prevent hepatitis B infections in two different monthly doses for patients with liver transplants. The company says patient data also revealed fewer side effects than with a competing drug.
Before heading to late-stage human clinical trials, Cubist plan to change how it makes and formulates HepeX-B, allowing for wide commercial manufacturing.
Hepatitis B has infected more than 2 billion people around the world, despite a vaccine introduced in 1982. The infection can lead to severe liver damage and a potential need for liver transplantation
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December 23rd, 2005
Saliva-Based Hepatitis C Test Developed
SourceURL:http://www.scidev.net
Wagdy Sawahel
Israeli scientists have developed a saliva-based test to detect the hepatitis C virus, and say it could be appropriate for mass screening programmes in developing countries.
Hepatitis C is common in the developing world, but the conventional method of detecting the virus in a blood sample is often inaccessible to poorer nations.
Current tests use a sample of the patient's serum, the liquid part of blood in which blood cells are suspended, and detect antibodies that the body produces in reaction to the virus.
But such tests are costly, complicated and rely on an array of medical equipment and skilled personnel.
Now researchers led by Arieh Yaari of Soroka University Medical Center, Israel, have shown that saliva can be used instead of serum to detect the virus.
They carried out their study on 37 dialysis patients, people without kidney function whose blood must be passed through a machine to filter out waste products.
Such patients have a high incidence of hepatitis C and may resemble ill people in developing countries in their immune response levels.
Yaari and colleagues report 100 per cent success at detecting hepatitis C in the saliva of patients who had symptoms of the disease. This is comparable to the results of testing serum.
In patients who had the virus but had yet to develop symptoms, the saliva test was accurate in 94 per cent of cases, while the conventional serum test detected only 63 per cent of infections.
Yaari's team say that as it is cheap and easy to obtain saliva samples, detecting hepatitis C infections using this technique might be economically and clinically important in developing nations.
They add that as the research involved only 37 patients, a larger study is needed to confirm the results. This could focus on a different high-risk population, for example people in developing countries, say the researchers.
They published their findings online on Monday (19 December) in the Journal of Virological Methods.
Reference: Journal of Virological Methods doi: 10.1016/j.viromet.2005.09.009
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Physicians Collecting Data on Drug at Prison
http://www.bismarcktribune.com/
By KATIE BROWN/Bismarck Tribune
Four Bismarck physicians are in the process of collecting data on the treatment of hepatitis C in North Dakota prisons.
Jeff Hostetter, Kent Martin, John Hagan and Olimpia Rauta presented initial findings at the Centers for Disease Control's National Viral Hepatitis Conference Dec. 8 in Washington, D.C.
Hostetter, the medical director for North Dakota prisons, said initial data was sent to the CDC who asked the four physicians to present their research. After presenting, Hostetter said they received approval to continue collecting data for further reports.
Hepatitis C is a blood-born pathogen transmitted mostly through needles during drug use or if a medical professional gets stuck by a needle.
Hostetter said the pathogen can be transmitted through sexual contact if bleeding occurs.
Martin and Hagan have been treating inmates for hepatitis C using a drug called Consensus Interferon instead of Peginterferon, the drug typically used to treat the disease.
Hostetter said their findings have been positive. He said the reason most patients with hepatitis C are not treated with Consensus Interferon, which is less expensive and has less side effects, is that Peginterferon only needs to be administered once a week.
Consensus Interferon must be administered three times a week which Hostetter said is possible for inmates. The state decided to use the drug because it is less expensive.
"For other people it is difficult to do the three injections per week," he said. "They forget or just don't come in for the shot. It's not effective if they don't get them."
He said the data he, Martin, Hagan and Rauta have presented and will continue to collect may show that Consensus Interferon should be used instead of Peginterferon.
"If you ask people, they'd rather have the inconvenience of three shots a week than the side effects of the Peginterferon," Hostetter said. "The problem is it doesn't work because people don't get the shots as often as they need to."
The side effects include a variety of ailments because Peginterferon stays in the body and acts as a toxin.
Hostetter said the data is simply medical charts that would be collected even if a study was not being conducted.
"We're not doing anything that wouldn't be done anyway," he said. "It's important to realize we're not experimenting on prisoners."
An increase in methamphetamine use is blamed for the rise in hepatitis C cases. Hostetter said in 2000, 10 percent of inmates in the North Dakota State Penitentiary were meth users. This year, 62 percent of inmates in the penitentiary are meth users.
"People who use meth have high-risk behavior," Hostetter said. "When they're tweaked out on meth they don't care about having clean needles."
He said due to the increase in hepatitis C, employees and inmates at North Dakota prisons are educated on keeping themselves safe. When inmates begin their sentence they go through an hourlong course informing them of how to avoid coming into contact with the disease.
Medical professionals at the prison and all other facilities are advised by the CDC to practice "universal precaution" meaning they handle every patient as if he or she could have hepatitis C or HIV.
Hostetter said 20 percent to 30 percent of hepatitis C patients get extremely sick right away and pass the disease through their system. The rest have it for life.
"You can live a relatively normal life with hepatitis C if you take care of yourself," he said. "If you drink alcohol, you have almost a 100 percent chance of eventually developing liver cancer."
Hostetter said there may be way for Consensus Interferon to be used more effectively than Peginterferon.
He said using a pump put in the body to deliver the injection on time is an option. So is having public health officials go out and give the injections to patients to be sure they get them on time.
"It's an ethical dilemma," he said. "Should we be letting patients deal with more side effects because it's more convenient."
(Reach reporter Katie Brown at 250-8225 or katie.brown@bismarcktribune.com.)
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