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Week Ending: January 28th, 2006
Alan Franciscus
Editor-in-Chief
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This Issue:
• Oral Glucose Tolerance Test Predicts Cirrhosis Prognosis
• MIGENIX to Initiate MX-3253 HCV Viral Kinetics Study in Treatment Naive Patients; CEO Message No. 17
• Hepatitis, 'The Silent Killer,' Driven Out of the Shadows
• Telithromycin Linked to Two Cases of Liver Failure and Implicated in a Third Case of Hepatitis
• Increased Risk of Hospital Mortality in Patients with Hep C
• Hep C Therapy with Interferon Alfa-2a and Ribavirin Is Safe in Practice
• Refractory Ascites Increases Mortality Post Liver Transplant
• Utah Actor, Writer Eric Tierney Dies at 26
• Fatigue May Be Misdiagnosed as Depression During Anti-HCV Therapy in HIV Coinfected
• Hepatitis C Protease Inhibitor Does Well in Early Clinical Trial
• Transgene Awarded EUR 1.3 M Grant for Hepatitis C Therapeutic Vaccine Programme
• Predictive Models for Liver Transplant Outcomes
• ALT Levels May Not Give True Picture of Liver Disease in HIV/HCV Coinfected, Suggests Study
• Vaccinate Infants of Hepatitis B Mothers, Say Experts
• AVI BioPharma Announces Hepatitis C Virus License Agreement with Chiron
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January 23rd, 2006
Oral Glucose Tolerance Test Predicts Cirrhosis Prognosis
SourceURL:http://www.gastrohep.com
This month's American Journal of Gastroenterology shows that oral glucose tolerance test is useful for evaluating the prognosis of cirrhosis, and diabetes mellitus is one of the most powerful independent negative predictor of survival.
Dr Tsutomu Nishida and colleagues evaluated whether oral glucose tolerance test was useful in evaluating the prognosis of liver cirrhosis.
The investigative team enrolled 56 patients with liver cirrhosis in a prospective cohort study.
In all cases, glucose tolerance was diagnosed by a 75 g oral glucose tolerance test according to World Health Organization criteria.
The relationship of clinical variables to the cirrhosis-related prognosis was investigated using univariate and multivariate regression models.
Diabetes mellitus was diagnosed in 21 subjects, impaired glucose tolerance in 13 subjects, and normal glucose tolerance in 22 subjects.
The cumulative survival rates of patients with liver cirrhosis and normal glucose tolerance were 95% at 5 years.
The investigators found that the survival rates of liver cirrhosis and impaired glucose tolerance at 5 years was 69%.
Liver cirrhosis and diabetes mellitus at 5 years had a 57% survival rate – American Journal of Gastroenterology
Liver cirrhosis and diabetes mellitus at 5 years had a 57% survival rate.
The survival rates of patients with liver cirrhosis and diabetes mellitus significantly differed from those with normal glucose tolerance.
The team used univariate analysis to demonstrate that serum albumin, total bilirubin, and prothrombin activity were prognostic factors.
Child-Pugh scores, and glucose intolerance were also highly significant prognostic factors.
Multiple regression analysis yielded albumin and diabetes mellitus as the most powerful independent negative predictors of survival.
Dr Nishida's team concluded, "Oral glucose tolerance test appears to be useful for evaluating the prognosis of cirrhotic patients."
Am J Gastroenterol 2006: 101(1): 70
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MIGENIX to Initiate MX-3253 HCV Viral Kinetics Study in Treatment Naive Patients; CEO Message No. 17
http://biz.yahoo.com
VANCOUVER, BC and SAN DIEGO, CA, Jan. 23 /CNW/ - MIGENIX Inc. (TSX: MGI - News; OTC: MGIFF - News), a clinical-stage developer of drugs for infectious and degenerative diseases, released the Company's 17th CEO Message today. The CEO Message provides an overview of the MX-3253 and CPI-226 clinical programs for 2006 and the first half of 2007, including the Company's plan to initiate a combination therapy viral kinetics clinical trial of celgosivir (MX-3253) in Hepatitis C virus (HCV) patients. Celgosivir is an orally administered, first- in-class alpha glucosidase 1 inhibitor, in development for the treatment of chronic HCV infections. The viral kinetics study is intended to demonstrate improved viral load kinetics (antiviral activity) in treatment-naive HCV patients when celgosivir is used in combination with interferon over a treatment period of up to 28 days. The study is expected to start early in the second quarter of calendar 2006, with results in the second half of calendar 2006.
Jim DeMesa, M.D., President and CEO of MIGENIX stated, "This viral kinetics study provides us another significant clinical result in HCV patients in 2006. In mid-year 2006 we will have results from our MX-3253 Phase IIb study in HCV 'non-responder' patients initiated in November 2005 with support from Schering-Plough. These results, along with the CPI-226 Phase III clinical results expected in the first half of 2007 provide us several near-term value driving opportunities".
To obtain a copy of the complete CEO Message, please visit the MIGENIX web site at www.migenix.com or contact Investor Relations at 1-800-665-1968, Extension 241.
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Hepatitis, 'The Silent Killer,' Driven Out of the Shadows
SourceURL:http://www.usatoday.com
By Anita Manning, USA TODAY
There was a time when Arline Loh of Wilmington, Del., didn't tell people she has hepatitis B.
"Now, I don't want to be silent," says Arline Loh about having hepatitis B.
"It carries such a stigma," says Loh, 57, an information technology expert who retired three months ago because of liver damage caused by the disease. "Hepatitis B is classified as an STD (sexually transmitted disease)."
It can be transmitted sexually, but Loh contracted the disease at birth from her mother, who carried the virus. About 90% of babies who are infected at birth develop chronic infection, compared with 6% of those infected later in life.
Until recent years, there was little the medical profession could do to help. Loh says the doctor who diagnosed her 17 years ago told her to "rest, and maybe you'll get better."
That has changed. Today there are five medications for hepatitis B, including two approved in 2005.
"Now, I don't want to be silent," Loh says. "Now there are drugs available to manage and treat this disease."
HEPATITIS BY THE LETTER
Hepatitis is an inflammation of the liver caused by a virus. Of the five known types of hepatitis virus, A, B and C are the most common in the USA:
Hepatitis A: Spread by the fecal-oral route, usually in areas with poor sanitation or by intimate contact with an infected person.
Hepatitis B: Spread through blood, usually through sexual contact, infected needles or from an infected mother to her baby at birth.
Hepatitis C: Spread through blood, often by needle sharing, needle sticks or from mother to child at birth.
Hepatitis D: Found in the blood, it exists only in the presence of hepatitis B and may increase severity of disease.
Hepatitis E: Most often spread in developing countries through contaminated water. Found in North Africa and South Asia but usually not in the USA.
Like hepatitis C, hepatitis B can cause long-term, chronic infection that can lead to severe liver damage, cirrhosis or liver cancer. The diseases can go undetected for decades because they often cause no symptoms until serious liver damage has occurred. "We're seeing an epidemic of both advanced cirrhosis and liver cancer," says Fred Poordad, chief of hepatology in the Center for Liver Disease and Transplantation at Cedars-Sinai Medical Center, Los Angeles. "I expect this to only get worse over the next 10 years" as the baby boomer population ages.
Hepatitis B disproportionately affects Asians and Pacific Islanders, who account for over half of the more than 1.3 million carriers of the virus, says hepatitis researcher Samuel So, director of the Asian Liver Center at Stanford University School of Medicine. Hepatitis rates among Asian-Americans are higher because the rates are high in many of their countries of origin, according to the Asian Liver Center.
China, where Loh was born, bears the world's highest rate of hepatitis B, he says. About one in 10 are infected, and about half a million people there die each year. "We call it the silent killer," So says. "Many people who are infected don't know it because they feel perfectly healthy."
Studies show that 10% to 20% of Asian-Americans have chronic hepatitis B infection. And carriers with no symptoms can unwittingly pass it on to their sexual partners or to their children. Routine blood tests don't include the specific test to detect hepatitis B, he says, so patients should ask for it.
Hepatitis is caused by viruses that attack the liver, causing inflammation. There are several types of the virus, labeled alphabetically A through E. But all of them initially can cause temporary symptoms such as fatigue, appetite loss, nausea and abdominal discomfort, dark urine and jaundice, or a yellowing of the skin and eyes.
There are vaccines for types A and B. An advisory committee of the Centers for Disease Control and Prevention last fall strengthened its recommendations to increase use of both vaccines. Now, all babies, not only those in states with high hepatitis rates, will be immunized against hepatitis A at 12 months to 23 months old. Also, hepatitis B vaccine will be required for all newborns and adolescents who missed their baby shots. Hepatitis B vaccine also is recommended for adults, especially those in high-risk groups.
Vaccination has helped reduce rates of hepatitis A from 143,000 cases in 2000 to 61,000 in 2003, and of hepatitis B from an average of 260,000 new cases a year in the 1980s, when the vaccine was licensed, to about 73,000 in 2003, the CDC says.
But the most common type of hepatitis is C, and for that there is no vaccine. As many as 4 million Americans and 170 million people worldwide may be infected, Poordad says. "There are still 30,000 to 40,000 new cases a year. Much of it stems from recreational drug use as well as immigrants to the U.S. who come already infected." He says hepatitis C is the most common cause of end-stage liver disease requiring transplantation.
Yet here, too, there is hope, he says. "There's been a flurry of research activity" investigating promising new drugs and drug cocktails, he says, and "we've gone from treatments that are less than 10% effective to therapies now that are 50% effective." Some strains of the virus can be eliminated in patients. "We feel if we can eradicate the virus," Poordad says, "we call that a cure."
That's what's happened for Robert Hartmann, 42, of Los Angeles, who owns the Improv Comedy Club chain. He contracted the disease after having dental work in 1977. It was undetected until 1992. "They didn't have a lot of treatment options," he says, so he didn't begin drug therapy for another 10 years. Now, after 16 months of combination drug therapy, he has been virus-free for a year and a half.
"That's why the message needs to get out that, guess what -- get tested for hep C because the cure rate goes up every year," he says. "The sooner you get tested, the better chance you have of beating this without damage to your liver."
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Telithromycin (Ketek) Linked to Two Cases of Liver Failure and Implicated in a Third Case of Hepatitis
SourceURL:http://www.medicalnewstoday.com
Three case reports of liver problems after taking the antibiotic telithromycin (Ketek®) are reported in Annals of Internal Medicine today.
Researchers at Carolinas Medical Center in Charlotte, N. C., say that one of the patients died; one required and received a liver transplant; and the third recovered from drug-induced hepatitis after the antibiotic was stopped.
The article, "Severe Hepatotoxicity of Telithromycin: Three Case Reports and Literature Review" will be published in the March 21, 2006, print edition of the journal. It was released early today online and is available to the public on Jan. 20, 2006, at acponline.org/journals/annals/hepatotoxicity.htm.
"These cases could represent an unusual clustering of a rare, idiosyncratic drug reaction at one medical center," said John S. Hanson, MD, an author and hepatologist with the liver transplant center at Carolinas Medical Center.
"However, the severity of liver injury in two of our patients warrants this report in the medical literature and will alert other physicians to this possible link with telithromycin."
Dr. Hanson said that, despite the three reports, "At this point, there is not enough data to indicate major changes in prescribing habits."
All cases have been referred to the FDA's Adverse Event Reporting System.
Patients taking Ketek® should report symptoms such as malaise, weakness, or jaundice to their prescribing physicians.
Telithromycin was approved by the U.S. Food and Drug Administration in 2004 to treat acute bacterial infections from chronic bronchitis, acute bacterial sinusitis and community-acquired pneumonia.
Telithromycin, an antibiotic derived from the macrolide class of antibacterial agents, appears effective against some pneumonia strains resistant to other older antibacterials such as penicillin.
In the three cases described in the Annals of Internal Medicine article, liver problems were observed after the patients began taking telithromycin. The reports do not prove that the antibiotic caused the liver impairment. But, in the article, the authors advise "caution in prescribing this drug pending further postmarketing surveillance data."
Patients in two of the three cases reported some use of alcohol, although no prior liver damage had been noted. Authors say that the relationship between telithromycin and alcohol use "warrants further study."
Carolinas Medical Center, an academic medical center teaching hospital, is a 861-bed facility of Carolinas HealthCare System. CHS is the largest healthcare system in the Carolinas and the third largest public system in the nation.
Early release article from Annals of Internal Medicine
Susan Anderson
sanderson@acponline.org
American College of Physicians http://www.acponline.org
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January 24th, 2006
Increased Risk of Hospital Mortality in Patients with Hep C
SourceURL:http://www.gastrohep.com/
Patients admitted to the hospital with alcohol-related diagnoses have longer hospital stays and are more likely to die in hospital if they have a diagnosis of Hepatitis C, finds this month's Journal of Hepatology.
Alcohol is known to act synergistically with chronic Hepatitis C virus infection to cause liver disease.
However, their combined effect on outcomes in acutely hospitalized patients is less clear.
Dr Judith Tsuia and colleagues examined the impact of Hepatitis C infection on hospital mortality.
The research team also investigated the impact and length of stay among hospitalized patients with Hep C and alcohol abuse problems.
The team retrospectively identified 6354 admissions to an urban, public hospital between 1996 and 2002.
The patients had discharge diagnoses related to alcohol dependence or abuse.
Hepatitis C diagnosis and other information were extracted from a clinical database.
Patients with Hepatitis C were twice as likely to die during hospital admission – Journal of Hepatology
The data extracted was tested for associations with death and length of hospital stay using multivariable regression techniques.
The researchers found that the prevalence of diagnosed Hepatitis C infection in this sample of patients with alcohol abuse was 15%.
Patients with Hepatitis C were about twice as likely to die during hospital admission.
The team noted a trend toward increased mortality even after adjustment for demographics, medical service, homelessness and comorbidities.
Length of stay was significantly longer for patients with Hepatitis C than those without.
Dr Tsuia's team concluded, "Patients admitted to the hospital with alcohol-related diagnoses have longer hospital stays and are more likely to die in hospital if they have a diagnosis of Hepatitis C."
J Hepatol 2006: 44(2): 262-6
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January 25th, 2006
Hep C Therapy with Interferon Alfa-2a and Ribavirin Is Safe in Practice
SourceURL:http://www.gastrohep.com
The latest Alimentary Pharmacology & Therapeutics reports that the efficacy and safety of pegylated interferon alfa-2a plus ribavirin in clinical practice is comparable with results of randomized-controlled trials.
Pegylated interferon alfa-2a plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials.
Dr Lee and colleagues from Canada examined the efficacy and safety of this therapy in routine clinical practice.
The research team conducted a prospective open-label programme.
The researchers gave treatment-naive patients with chronic Hepatitis C pegylated interferon alfa-2a 180 μg/week plus ribavirin 800 mg/day for 24 or 48 weeks.
The negative predictive value of an early virological response at week 12 was 94% – Alimentary Pharmacology & Therapeutics
In total, 508 patients were enrolled, of which 334 were non-cirrhotic, and 174 were cirrhotic.
In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics.
The team noted that sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% and 72%, respectively.
The researchers found that the corresponding values for cirrhotic genotype 2 and 3 were 66% and 44%.
The negative predictive value of an early virological response at week 12 was 94%.
Predictive factors for sustained virological response on multivariate analysis were genotype 2 and 3, and low viral load and degree of fibrosis.
The team observed that the rates of serious adverse events and adverse events inducing withdrawal were comparable with the phase III trials.
Dr Lee's team concludes, "Efficacy and safety of pegylated interferon alfa-2a plus ribavirin in clinical practice is comparable with results of randomized-controlled trials."
Aliment Pharmacol Ther 2006: 23(3): 397
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Refractory Ascites Increases Mortality Post Liver Transplant
SourceURL:http://www.gastrohep.com
Research in the recent issue of the American Journal of Transplantation shows a 9 times higher mortality rate in patients following refractory ascites development after liver transplantation, exacerbated by Hep C recurrence.
Dr Nishidaa and colleagues conducted a retrospective study of 1058 liver transplant recipients.
The research team determined the incidence, etiology, timing, clinical features and treatment of refractory ascites.
Survival following refractory ascites was poorer with Hep C recurrence – American Journal of Liver Transplantation
The researchers established the risk factors for refractory ascites development, and the predictors of refractory ascites disappearance.
In addition, the team assessed the predictors of survival following refractory ascites, and the impact of refractory ascites on patient survival.
The team consulted 62 patients that had developed refractory ascites, and noted that its disappearance occurred in 27 cases.
Patients having Hepatitis C virus had a significantly higher hazard rate of developing refractory ascites.
The team reported that no other baseline characteristic was associated with refractory ascites.
The researchers undertook a stepwise regression analysis of the hazard rate of refractory ascites disappearance.
Following this analysis, the team found 2 significant factors contributed to developing refractory ascites.
The team noted that Hepatitis C virus recurrence implied a poorer outcome, whereas an unknown reason implied a favourable outcome.
In addition, survival following refractory ascites was significantly poorer among patients having bacterial peritonitis or Hepatitis C virus recurrence.
The mortality rate was 9 times higher in patients following refractory ascites development, while it was ongoing.
The researchers found that if the refractory ascites disappeared, then the additional risk of death also disappeared.
Dr Nishidaa's team concluded, "This study illustrates the importance of developing an optimal treatment strategy to effectively treat refractory ascites if it develops and to prevent Hepatitis C recurrence."
Am J Transplant 2006: 6(1): 140
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Utah Actor, Writer Eric Tierney Dies at 26
SourceURL:http://kutv.com
SALT LAKE CITY Utah actor and writer Eric Tierney has died of liver failure associated with hepatitis B.
He was 26.
Tierney died early Monday, just eight hours after the final performance of ``Love! Valour! Compassion!'' He had performed last week in the first four shows of the Wasatch Theatre Company's production at the Rose Wagner Performing Arts Center before he fell ill and was admitted to the hospital on Thursday.
Director Jerry Rapier, who filled in for Tierney as Perry, one of eight gay New Yorkers in the play, joined about three dozen friends and family members at the hospital Sunday evening.
"In theater, you spend such a concentrated period of time together, you become a family,'' Rapier said.
Tierney, a graduate of West Jordan High School and the University of Utah's Acting Training Program, wrote an events column, "The Gay Agenda,'' plus theater reviews and arts stories for Salt Lake Metro, a biweekly gay and lesbian newspaper.
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Fatigue May Be Misdiagnosed as Depression During Anti-HCV Therapy in HIV Coinfected
SourceURL:http://www.aidsmap.com
Edwin J. Bernard
Fatigue is more than twice as prevalent as depression during anti-hepatitis C (HCV) treatment in HIV-positive individuals, according to a study presented to the Second International Workshop on HIV and Hepatitis Coinfection, held in Amsterdam earlier this month. Lead author, Dr Kristina Jones of Weill Cornell Medical Center, New York, suggests that fatigue is being misdiagnosed as depression in these individuals and recommends using standardised questionnaires so that the coinfected patient can be correctly assessed and treated. Her findings also suggest that coinfected individuals can be treated safely with anti-HCV therapy despite the development of depression, provided psychiatric care is integrated with medical care.
The psychological side-effects of current anti-HCV treatments are a frequent reason for discontinuation, although there are few data regarding the prevalence of depression and fatigue during anti-HCV therapy.
Consequently, Dr Kristina Jones of the Department of Psychiatry, The New York-Presbyterian Hospital, Weill Cornell Medical Center, set up a substudy of 93 HIV/HCV coinfected patients who were enrolled in a prospective trial of the optimal management of anaemia and neutropenia (comparing dose reduction versus growth factor supplementation) in individuals receiving pegylated interferon alfa-2b (Viraferon-Peg / Peg-Intron) and ribavirin (Copegus / Rebetol / Virazole).
A total of 72 (77%) men and 21 (23%) women were included in the study, 43% of whom were African American, 30% of whom were Caucasian, and 22% of whom were Hispanic. Patients with a history of severe depression (defined as a history of hospitalisation, electro-convulsive therapy or history of serious suicide attempt) were excluded, as were those who were active substance abusers.
At baseline, 18 individuals (19%) reported a history of depression, six (6%) reported a history of attempting suicide and one (1%) reported a history of suicidal ideation. HIV viral load was below 400 copies/ml in 68 (73%) and HCV viral load was over one million copies in 46 (49%) patients.
Fatigue and anaemia
A total of 65 (70%) experienced fatigue during the study, and this developed very early (during week 1) for the majority of participants, and peaked at week 4. Prevalence of fatigue was strongly associated with anaemia: of the 44 individuals diagnosed with anaemia, 34 (77%) experienced fatigue during the study. Only 20% of non-anaemic individuals complained of fatigue, resulting in a 3.8-fold increase in the prevalence of fatigue amongst anaemic participants compared with non-anaemic participants.
No association was found between depression and fatigue, and although one person discontinued anti-HCV treatment early due to fatigue, fatigue was not statistically significantly associated with early discontinuation. In addition, there was no association between depression and anaemia: 27% of anaemic patients were depressed, whereas 77% of anaemic patients were fatigued.
Depression
A total of 31 (33%) were diagnosed with depression using a standardised questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Of these 31, 25 (81%) experienced both depression and fatigue. The 33% prevalence of depression found in this study is similar to the 35% prevalence of depression in monoinfected individuals on anti-HCV therapy (Kraus, 2003).
Depression was slower to develop in comparison to fatigue, but in the majority of cases occurred by week 12. Of the 31 patients who became depressed, seven of these had a history of depression and 24 did not. These observations suggest that 77% were de novo depression.
Despite the 19% pre-existing prevalence of depression and although there was one episode of suicidal ideation, there were no suicide attempts or completed suicides, and the person who experienced suicidal ideation did not discontinue the study early.
In total, there were two early discontinuations due to depression. However, depression was not found to be a statistically significant predictor of early discontinuation. In fact, early discontinuation was found to be associated with anaemia and neutropenia, but not with psychiatric side-effects.
"A bit of a shock"
Dr Jones told the conference that she suggests all patients ought to be "checked for depression at baseline and by week 4 using standardised questionnaires to detect depression," adding that "nurses could do these questionnaires, saving the doctor's time. Using standardised questionnaires would enable us to detect those one-third of patients who are going to suffer from depression during treatment and who are going to need treatment."
She added that "my data don't support the idea of prophylactic treatment of depression. Since only a third develop depression", this would result in over-treatment.
She also concluded that her findings suggest that HIV/HCV coinfected individuals can be treated safely with anti-HCV therapy despite the development of depression, "provided that psychiatric care is integrated with medical care."
Dr Marion Peters, from the University of California in San Francisco, and a member of the on-stage panel that discussed Dr Jones' data added that she thought this were "very important data" and questioned Dr Jones further about the differences between fatigue and depression. "We say 69% of patients on [anti-HCV therapy] need antidepressants," Dr Peters said, before asking: "Is it just that we're terrible psychiatrists? Are we calling fatigue depression?"
Dr Jones replied that "the critical point of the study is that's it's hard to tell the difference between fatigue and depression unless you ask the nine questions necessary for the diagnosis of depression using DSM-IV. In the present moment of fatigue a patient will report being depressed. The fascinating thing for me was that I thought it was going to be the depressed patients who got depressed again, but it wasn't. And that was a bit of a shock."
References
Jones K et al. High prevalence of fatigue and depression in HIV/HCV coinfected patients treated with interferon and ribavirin. 2nd Intl Workshop HIV/HCV Coinfection, Amsterdam, abstract 38, 2006.
Kraus MR et al. Psychiatric symptoms in patients with chronic hepatitis C receiving interferon alfa-2b therapy. J Clin Psychiatry 64 (6), 708 - 714, 2003.
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Hepatitis C Protease Inhibitor Does Well in Early Clinical Trial
www.aidsmap.com
Michael Carter
A hepatitis C virus protease inhibitor has done well in early clinical trials. The oral drug, VX-950, which is being developed by Vertex Pharmaceuticals, achieved significant reductions in hepatitis C viral load when used in combination with pegylated interferon alfa-2a (Pegasys).
Current treatment for hepatitis C virus involves weekly injections with pegylated interferon and daily doses of ribavirin. This treatment is not universally effective and has unpleasant, often intolerable side-effects. Coinfection with hepatitis C is common amongst HIV-positive individuals and the current standard of treatment is less effective in coinfected individuals than in patients who are only infected with hepatitis C.
In the phase Ib study, the combination of VX-950 and Pegasys produced a significant reduction in hepatitis C viral load in the first two days of treatment, and by day 14, 50% of patients provided with the investigational therapy had an undetectable hepatitis C viral load (below 10 copies IU/ml).
The 14-day randomised, blinded, placebo-controlled trial involved 20 individuals with hepatitis C virus genotype 1. This is the commonest and hardest to treat of the hepatitis C genotypes. Patients were randomised to receive VX-950 at a dose of 750mg every eight hours in combination with Pegasys, the same dose of VX-950 alone, or Pegasys alone. On entry to the study, patients had a median hepatitis C viral load of over four million copies IU/ml.
Analysis of preliminary results showed that individuals taking the investigational protease inhibitor with Pegasys had a median fall of 5.5 log10 in their viral load, compared to a median fall of 4 log10 in patients taking VX-950 alone and 1 log10 in individuals randomised to take Pegasys monotherapy.
No serious side-effects were reported and patients taking VX-950 reported only mild adverse events.
Vertex have announced plans for larger phase II clinical trials which will investigate the safety and effectiveness of VX-950 in combination with both Pegasys and ribavirin. The trial will start in the next few months and involve 200 patients.
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Transgene Awarded EUR 1.3 M Grant for Hepatitis C Therapeutic Vaccine Programme
SourceURL:http://www.prnewswire.com
STRASBOURG, France, January 25 /PRNewswire-FirstCall/ -- Transgene S.A. (Eurolist Paris: FR0005175080) announces today that it has been awarded funding by the Lyon Biopole Competitiveness Cluster (Pole de competitivite) for the development of its therapeutic vaccine candidate against hepatitis C chronic infection (HCV). This funding is expected to total EUR 1.3 million over the next three years and will cover 30% of the research and development costs for this programme.
The grant aims at strengthening the development of Transgene's vaccine candidate TG4040 (MVA-HCV). TG4040 is currently undergoing preclinical studies and should enter Phase I/II trial by mid-2006 to treat patients non responding to standard therapy. The TG4040 development programme is carried out by Transgene's infectious diseases research team based in Lyon, France. Research units of INSERM, CNRS, Grenoble University Hospital and Lyon Civil Hospitals will also participate in the subsidised programme.
"We are extremely pleased to be among the very first projects selected by Lyon Biopole and to receive government financial support for the development of our innovative approach to treat patients chronically infected by hepatitis C," stated Philippe Archinard, Chief Executive Officer of Transgene.
About Hepatitis C:
Hepatitis C infection is a major public health problem with around 170 to 200 million people infected worldwide. An estimated 500,000 people are infected in France and only 50% of them are diagnosed. About one third of diagnosed patients receive a standard treatment efficient in roughly 50% of cases.
About Transgene:
Transgene is a France-based biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The company has three compounds in Phase II trials and one compound in Phase I studies. Transgene has bio-manufacturing production capacities for viral-based vectors and technologies available for out-licensing. For further information about Transgene, please visit http://www.transgene.fr
About France Competitiveness Clusters:
"Competitiveness clusters" are designed to spark growth of industrial activities and jobs and to strengthen the regions. In September 2005, a call for projects was launched to select a first series of proposals for the creation of clusters in the area of structuring technologies and industrial activities in which France is specialised or has acknowledged potential. Based upon public-private partnerships, eligible proposals may involve businesses, research centres and higher education hubs, financial institutions, regional authorities, France's central government and Europe.
Forward-looking statement:
This press release contains forward-looking statements referring to the planned development and clinical testing of one of Transgene's therapeutic vaccine candidates. However, product development and clinical testing depend on a variety of factors, including the timing and success of patient enrolment and the risk of unanticipated adverse patient reactions. Furthermore, as is the case with all biopharmaceutical products under development, results from future studies with more data may show less favorable outcomes than prior studies. There is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. In addition, as previously communicated, Transgene's currently available funding does not ensure that it can continue operations after 2007, and thus additional financing may be necessary to carry out planned development and testing. For a more detailed description of the risks and uncertainties involved in the development and clinical testing of Transgene's product candidates, see Transgene's Annual Report on Form 20-F and its other reports on file with the U.S. Securities and Exchange Commission.
Press Contacts:
Philippe Poncet
+33-3-88-27-91-21
http://www.transgene.fr
Transgene Capital
Shaun Brown
Mary Clark
+44-(0)20-7307-5330
MS&L
Estelle Guillot-Tantay
Tiphaine Hecketsweiler
+33-1-53-70-74-93
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January 26th, 2006
Predictive Models for Liver Transplant Outcomes
SourceURL:http://www.gastrohep.com
The latest Lancet reports that 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centers, and provide a means of assessing post-transplantation mortality risk.
Mortality after liver transplantation depends on heterogeneous recipient and donor factors.
Dr Andrew Burroughs and colleagues assessed risk of death and to develop models to help predict mortality after liver transplantation.
The research team analyzed data from 34,664 first adult liver transplants from the European Liver Transplant Registry.
The researchers identified factors associated with mortality at 3-months, and 12-months after transplantation.
The team used multivariable logistic regression models to generate mortality scores for each individual.
Model discrimination and calibration on an independent validation dataset was assessed.
Increased mortality at 3-months post-transplantation was associated with acute liver failure – The Lancet
The team found that 12% of individuals in the 3-month training sample had died by 3 months.
Compared with those transplanted in 2000 to 2003, those transplanted earlier had a higher risk of death.
The researchers observed that increased mortality at 3-months post-transplantation was associated with acute liver failure.
Donor age older than 60 years, compatible or incompatible donor-recipient blood group, and older recipient age were also associated with acute liver failure.
In addition, liver failure was associated with split or reduced graft, total ischemia time of longer than 13 hours, and low United Network for Organ Sharing score.
However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, Hepatitis C or primary biliary cirrhosis were associated with improved early outcomes.
The team noted that donor age 40 years or younger, Hepatitis B, and larger size of transplant center were also associated with improved early outcomes.
The 3-month mortality score discriminated well between those who did and did not die in the validation sample.
The researchers noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint.
Dr Burroughs concludes, "The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centers."
"Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups."
Lancet 2006: 367: 225-32
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ALT Levels May Not Give True Picture of Liver Disease in HIV/HCV Coinfected, Suggests Study
SourceURL:http://www.aidsmap.com
Michael Carter
The majority of HIV-positive individuals coinfected with hepatitis C virus who, according to a key blood test, have normal liver function are, in fact, suffering from mild to severe liver damage, according to an Italian study published in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
Using liver biopsies the researchers established that 25% of patients with normal alanine aminotransferase (ALT) levels - a key marker of liver function - have such severe liver damage that they require anti-hepatitis C treatment, with 13% having cirrhosis, permanent scarring of the liver.
Doctors in Milan conducted a retrospective study, involving 326 HIV/hepatitis C coinfected patients who had a liver biopsy between 1997 and 2003. None of the patients had taken anti-hepatitis C treatment. The patients were divided into groups according to whether they had persistently normal or elevated ALT levels in the twelve months before their liver biopsy. The stage of liver disease was then compared between the two groups and the investigators conducted statistical analysis to see if there were any factors that predicted which patients with normal ALT levels were more likely to have liver damage.
In total 15 individuals (24%) had persistently normal ALT levels. There were no significant differences between these patients and those with elevated ALT levels with respect to age, gender, HIV risk group, CD4 cell count, or the use of HIV therapy. Individuals with normal ALT scores, however, were statistically more likely to have an undetectable HIV viral load (63% vs 35%, p = 0.014).
Unsurprisingly, liver biopsies showed that patients with normal ALT levels were much more likely to have no, or very mild fibrosis (75% vs. 31%, p = 0.0001).
However, the investigators noted that 25% of individuals whose ALT blood tests suggested that they had normal liver function in fact had a degree of liver fibrosis (score 2 - 6) severe enough to require anti-hepatitis C treatment. In addition, two further patients (8%) with normal ALT levels had cirrhosis (level 7 fibrosis or above).
The investigators then looked at the characteristics of the patients with normal ALT scores whose liver biopsies had mild to severe fibrosis. They found that these individuals were older (p = 0.01) and had a lower CD4 cell count (below 500 cells/mm3, p = 0.03).
Finally, investigators conducted long-term follow-up of patients with persistently normal ALT levels. The median duration was five years, and 91% of patients did not show any progression of their HIV disease, with 33% remaining HIV treatment-naive. However, 42% of patients had experienced hepatitis C disease progression including six patients who required anti-hepatitis C therapy, one patient who died of liver disease and one individual who developed decompensated cirrhosis.
"These findings highlights the threat hidden by persistently normal ALT levels, which are too often considered a sign of well-balanced liver status in HIV-positive subjects with chronic hepatitis C virus infection", conclude the investigators.
Reference
Uberti-Foppa, C et al. Liver fibrosis in HIV-positive patients with hepatitis C virus: role of persistently normal alanine aminotransferase levels. J Acquir Immune Defic Syndr 41: 63 - 67, 2006.
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January 27th, 2006
Vaccinate Infants of Hepatitis B Mothers, Say Experts
SourceURL:http://www.eurekalert.org
Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis; BMJ Online First
Immunising newborn infants of mothers with hepatitis B prevents infection being transmitted from mother to child, finds a study published online by the BMJ today.
There are around 350 million hepatitis B carriers worldwide. The virus is transmitted by contact with blood or body fluids of an infected person. Mother to child transmission around the time of birth is common and accounts for up to half of all carriers.
Researchers analysed randomised trials to assess the beneficial and harmful effects of hepatitis B vaccines (active production of antibodies) and hepatitis B immunoglobulin (passive transfer of antibodies) in newborn infants of mothers positive for hepatitis B surface antigen.
They found that hepatitis B vaccine, hepatitis B immunoglobulin, or the combination of vaccine plus immunoglobulin given to the newborn infants of mothers positive for hepatitis B surface antigen prevents the occurrence of hepatitis B. Furthermore, the combination of vaccine plus immunoglobulin was superior to vaccine alone.
There was no difference between the two types of vaccine currently available.
"Although this study confirms that vaccines and immunoglobulin are effective, more research is needed to identify the optimal dose and treatment schedule of hepatitis B immunisation," conclude the authors.
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AVI BioPharma Announces Hepatitis C Virus License Agreement with Chiron
http://www.genengnews.com
AVI BioPharma, Inc. (Nasdaq:AVII), today announced that it has entered into an agreement with Chiron Corp. granting AVI a nonexclusive license to Chiron's patents and patent applications for the research, development and commercialization of antisense therapeutics against hepatitis C virus (HCV). Chiron scientists were the first to clone HCV, and the company has been granted more than 100 HCV-related patents.
The license further strengthens AVI's patent position on its HCV antisense product candidates, which are already covered by issued U.S. patent claims. AVI's lead NEUGENE(R) antisense compound for HCV, AVI-4065, is currently being evaluated in a multicenter exploratory safety and efficacy clinical trial in the U.S. In conjunction with the license agreement, AVI will issue Chiron shares of AVI common stock as an initial license fee payment. Other financial terms of the agreement were not disclosed.
"This agreement with Chiron positions AVI to move forward in our HCV development program with confidence and clarity around intellectual property," said Denis R. Burger, Ph.D., chief executive officer of AVI. "The addition of the HCV patents licensed from Chiron to AVI's own patents provides a solid proprietary base in the HCV field for AVI and our eventual commercial partners."
The multicenter clinical study currently underway is designed to assess the safety, tolerability, pharmacokinetics and viral response to daily subcutaneous administration of AVI-4065 among healthy volunteers and patients with chronic active HCV. AVI recently reported completion of the first phase of this study with favorable safety, tolerability and pharmacokinetic profiles and is now in the second efficacy phase of the program. Additional data are expected from this trial later in the first quarter.
The principal investigator of the clinical trial is Mark Holodniy, M.D., F.A.C.P., professor of medicine at Stanford University School of Medicine and director of the Department of Veterans Affairs Public Health Research & Consultation Program.
About Hepatitis C
Chronic HCV infection causes an inflammation of the liver that can result in the development of cirrhosis, liver cancer or liver failure. According to the World Health Organization, approximately 170 million people worldwide are chronically infected with HCV. It is the most common chronic blood-borne infection in the developed world and the leading cause of liver transplants in the U.S. The CDC estimates that approximately 3.9 million Americans have been infected with HCV, of whom 2.7 million are chronically infected.
The Hepatitis Foundation International estimates that between 8,000 and 10,000 people die annually in the U.S. from HCV-related cirrhosis or liver cancer. The current treatment for HCV, 24 to 48 weeks of therapy with pegylated interferon alpha and ribavirin, is successful in less than half of the patients infected with genotype 1 HCV, the most common form of the virus in the U.S. Furthermore, this treatment has numerous side effects, some of them severe, which makes it difficult for almost half of initially treated patients to tolerate the recommended dosages and duration of treatment.
About AVI BioPharma
AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using third-generation NEUGENE antisense drugs. AVI's lead NEUGENE antisense compound is designed to target cell proliferation disorders, including cardiovascular restenosis, cancer and polycystic kidney disease. In addition to targeting specific genes in the body, AVI's antiviral program uses NEUGENE antisense compounds to combat disease by targeting single-stranded RNA viruses, including West Nile virus, hepatitis C virus, dengue virus and Ebola virus. AVI has introduced a NEUGENE-based exon-skipping technology called ESPRIT therapy. More information about AVI is available on the company's Web site at http://www.avibio.com.
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: The statements that are not historical facts contained in this release are forward-looking statements that involve risks and uncertainties, including, but not limited to, the results of research and development efforts, the results of preclinical and clinical testing, the effect of regulation by the FDA and other agencies, the impact of competitive products, product development, commercialization and technological difficulties, and other risks detailed in the company's Securities and Exchange Commission filings.
CONTACT:
AVI Contact:
AVI BioPharma, Inc. Michael Hubbard, 503-227-0554 hubbard@avibio.com
or
Investor Contacts: Lippert/Heilshorn & Associates Inc. Bruce Voss or Jody Cain, 310-691-7100 bvoss@lhai.com or jcain@lhai.com
or
Press Contact: Waggener Edstrom Worldwide Bioscience and Healthcare Practice Jenny Moede, 503-443-7000 jmoede@waggeneredstrom.com
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