« October 2006 | Main | December 2006 »

November 24, 2006

Oglufanide Tested as Potential Hepatitis C Treatment

An Australian clinical trial is testing a novel strategy for battling Hepatitis C. Physicians are starting to treat Hepatitis C patients with oglufanide, a drug capable of regulating the body's immune response.

Drug in New Hepatitis C Clinical Trial
Tuesday November 14, 11:26 pm ET

BRISBANE, Australia, Nov. 14 /PRNewswire/ -- Physicians at Brisbane's Princess Alexandra Hospital have treated the first two patients in a clinical trial designed to test a new strategy for defeating hepatitis C viral infection, one of the toughest infectious diseases in the modern world.

ADVERTISEMENT
Implicit Bioscience's drug, oglufanide, which works as a regulator of the body's immune response, is being given to patients with chronic hepatitis viral infection.

"The drugs currently in use fail to control this disease in about one half of all patients," said Dr. Ian Frazer, Implicit's Chief Scientific Officer. "So there is a compelling need for new and better therapies, and we hope that oglufanide may control or reverse the suppression of the immune system which the hepatitis virus uses to defeat our normally healthy defences."

Dr. Frazer is well known as the co-inventor of the recently approved vaccine for papillomavirus which is designed to prevent cervical cancer.

Dr. Elizabeth Powell, who is the Principal Investigator for the trial which will be recruiting patients into 2007, welcomed the opportunity to study the action of oglufanide in her busy liver diseases clinic at the Princess Alexandra Hospital. "It is an important opportunity for patients to be involved in a new trial such as this, in which new treatment prospects are explored."

Oglufanide was originally developed to treat severe infectious disease in Russia (where it is a registered pharmaceutical), and was extensively studied in cancer clinical trials in the United States before being acquired by the privately-owned Brisbane biotech company Implicit Bioscience Pty Ltd in 2005. Oglufanide regulates the body's innate immune response to defeat invading germs and cancer cells. The drug is also under development by Implicit for severe respiratory diseases such as influenza (including pandemic disease) and ovarian cancer. Oglufanide has US Investigative New Drug status and Orphan Drug designation for cancer.

Source: Implicit Bioscience Inc.

Posted by Editors at 09:52 AM --- Printer-friendly version | Comments (0)

New Method for Improving HCV/HIV Co-Infection Response

Spanish researchers recently investigated the growing trend of basing ribavirin dosages on weight for those co-infected with HIV and Hepatitis C. Their results demonstrate substantial benefit to weight-dosing, and confirm the need for this individualized treatment approach.

Weight-based ribavirin dosing achieves high success rates in hepatitis C/HIV co-infected patients

Gus Cairns, Tuesday, November 21, 2006
aidsmap.com

Increasing the dose of ribavirin in interferon/ribavirin therapy and basing it on the patient’s weight can achieve impressive treatment success rates, approaching if not yet equalling those seen in HIV-uninfected patients, Spanish researchers reported last week.

Study results from the PRESCO trial of pegylated interferon and eight-based ribavirin were presented by Vincent Soriano to the Eighth Glasgow International Congress on Drug Therapy in HIV Infection in Glasgow.

PRESCO is a trial of hepatitis C (HCV) therapy in reasonably well patients: participants had to have a CD4 cell count of over 300 cells/mm3, were not allowed to take AZT (zidovudine, Retrovir) or ddI (diadosine, Videx) and were not cirrhotic. It was an open-label study, with no comparison with other regimens.

The study gave patients 180 micrograms of pegylated interferon alfa-2a (Pegasys) per week and combined it with a daily dose of either 1000mg ribavirin if the patient weighed less than 75kg or 1200mg if they weighed more.

The original PRESCO protocol, devised in December 2002, prescribed 48 weeks of treatment for patients with genotypes 1 or 4 of HCV and 24 weeks for genotypes 2 or 3. However after the APRICOT study results came out, this was amended in August 2004 to allow 72 weeks of treatment for genotypes 1 or 4 and 48 weeks for 2-3.

In the end 192 patients with genotype 1/4 took 48 weeks of treatment and 45 for 72 weeks. Ninety-six patients with genotype 2/3 took treatment for 24 weeks and 56 for 48 weeks.

Presenter Vincent Sorriano commented that it had been difficult to persuade patients to extend their treatment period and results were “hampered by voluntary withdrawal”.

The Sustained Viral Response (SVR) rates were 49.6% for all patients, 35.6% for genotype 1, 32.6% for genotype 4 and 72.4% for genotype 3 – there were virtually no genotype 2 patients in the study.

Extended treatment did convey additional benefit. SVR results for patients with genotypes 1/4 were 53% for patients who took treatment for 72 weeks and 82% for patients with genotypes 2/3 who took 48 weeks of treatment.

Hepatitis C treatment can appear to be successful, with undetectable HCV viral loads at the end of treatment, but it can then relapse and HCV can reappear, which is why the SVR is measured twelve weeks after the end of treatment and is the measure of treatment success. The relapse rate for patients with genotype 1 was 35% and with genotype 4 was 20%, with few relapsers for genotypes 2/3.

About a third (34.6%) of patients discontinued their treatment with 8.2% doing so for adverse events and 16.4% withdrawing voluntarily. About 15% of patients had their interferon dose reduced for toxicity and about 20% of patients had their ribavirin dose reduced.

The dose-limiting toxicity of ribavirin is usually anaemia. Four had to stop treatment at twelve weeks for this reason, four at 24 weeks and one at 48 weeks.

There was one death attributed to treatment in the trial – a patient who committed suicide, presumably due to the depression which is a notorious side-effect of interferon.

Sorriano contrasted his trial results with those from two previous trials: the APRICOT trial (Torriani), which is the largest study ever conducted in HIV/HCV co-infected patients but used an 800mg fixed dose of ribavirin, and the PISG trial (Fried) which used weight-based ribavirin but in monoinfected patients.

Sorriano said that PRESCO was the largest trial using weight-based ribavirin conducted in co-infected people so far and said that his results justified using this approach in future.

Posted by Editors at 06:28 AM --- Printer-friendly version | Comments (0)

November 22, 2006

Hepatitis C Toothbrush Contamination

Separating personal items used by a person with Hepatitis C from other household members to prevent transmission may seem overly cautious. However, a recently published study confirms the risk of spreading Hepatitis C by sharing a toothbrush.

Hepatitis C – contamination of toothbrushes: myth or reality?

Chronic hepatitis C patients are advised not to share toothbrushes, razors, nail-scissors or other personal articles that potentially may have been in contact with blood, with others. This study examines the contamination of toothbrushes in patients with chronic hepatitis C as a model for a possible unconventional way of transmission. In 30 patients with chronic hepatitis C, 2 mL of saliva (before and after toothbrushing) and the toothbrush rinsing water after toothbrushing were tested for HCV-RNA. Saliva before and after toothbrushing was positive for HCV-RNA in nine (30%) and 11 patients (36.7%), respectively. Twelve of the toothbrush rinsing water specimens (40%) tested HCV-RNA-positive. In six of these 12 patients, the 'native' saliva had been negative for HCV-RNA. Patients with HCV-RNA-positive toothbrush rinsing water showed no significant differences from those with negative rinsing water with respect to certain clinical, biochemical and virological parameters. In conclusion, our study demonstrates a contamination with HCV-RNA of a considerable portion of toothbrushes used by hepatitis C patients, suggesting at least a theoretical risk of infection by sharing these objects and strengthening the recommendations to take care of a clear separation of these personal care objects between patients and their household members.

Source:
Journal of Viral Hepatitis
Volume 13 Page 571 - September 2006
doi:10.1111/j.1365-2893.2006.00735.x
Volume 13 Issue 9

Posted by Editors at 09:22 AM --- Printer-friendly version | Comments (0)

November 10, 2006

Study Announcement for Advanced Cancer and Liver Dysfunction

Western medicine has typically had little to offer those with end stage liver disease, which can be marked by advanced cancer and irregular liver function. In the following press release, you will learn more about a recently announced Phase 1 study examining the effects an experimental drug has on this serious combination of conditions.

Summary: PHI-50 NCI#6432: A Phase I Pharmacokinetic Study of PS-341 in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEP-Sponsored Organ Dysfunction Working Group

You have been asked to participate in this research study because you have advanced cancer that is no longer responding to standard treatment and your liver function is normal or is no longer normal. The purpose of this research study is to find out the highest dose of an experimental drug PS-341 that can be given to subjects with advanced cancer and abnormal liver function without causing unmanageable side effects. Additionally, researchers will be looking to find out how the study drug moves through the body. Y

Patient Inclusion/Exclusion Criteria:

- See http://clinicaltrials.coh.org for additional information.

Contact:

City of Hope National Medical Center
1500 East Duarte Road
Duarte, CA 91010-3000
Telephone: 866-896-HOPE (4673)

Source: www.centerwatch.com

Posted by Editors at 11:04 AM --- Printer-friendly version | Comments (0)

November 09, 2006

Next Generation Hepatitis C Drug Begins Clinical Trial

Designed to have more anti-viral and immune-stimulating activity, Maxy-alpha is Roche's next generation interferon alpha for Hepatitis C treatment. Roche has initiated a Phase 1a study to determine the safety and efficacy of this drug.

Maxygen's Next-Generation Interferon Alpha Enters Phase 1a Clinical Trial
PR Newswire

REDWOOD CITY, Calif., Nov. 7 /PRNewswire-FirstCall/ -- Maxygen, Inc. announced today that Roche has initiated a Phase Ia clinical trial in New Zealand to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Maxy-alpha, a next-generation interferon alpha for the treatment of hepatitis C virus infection.

The Phase Ia clinical trial is a double-blind, dose-escalation, controlled study of a single sub-cutaneous administration of Maxy-alpha in healthy volunteers with both placebo and PEGASYS(R) (peginterferon alfa-2a (40KD)) control groups. Maxy-alpha, also known as R7025, Roche's internal designation for the molecule, is a novel PEGylated interferon alpha variant created through the use of Maxygen's proprietary MolecularBreeding(TM) directed molecular evolution technologies. Maxy-alpha has been designed to have more anti-viral activity against the hepatitis C virus and be more effective in stimulating immune responses to help combat the infection. Preclinical data comparing Maxy-alpha to PEGASYS(R) demonstrated that Maxy-alpha has increased anti-viral and immune stimulatory activity compared to PEGASYS(R). Roche and Maxygen worked together to PEGylate Maxy-alpha to ensure comparable pharmacokinetics and dosing convenience to Roche's currently marketed PEGylated interferon alpha, PEGASYS(R).

Maxygen will receive a $2 million dollar milestone payment for the commencement of the Phase Ia trial.

"Maxy-alpha is the first 'shuffled' protein to enter clinical development," said Russell Howard, Chief Executive Officer of Maxygen. "This demonstrates how Maxygen's proprietary technologies can be used to specifically enhance desired properties of potential protein drugs. We designed this molecule to have greater potency over the currently marketed interferon alpha drugs in the hopes of addressing the large percentage of patients that are not effectively served by current therapies. We are hopeful that the forthcoming clinical trials of Maxy-alpha will demonstrate a significant improvement in the treatment of hepatitis C virus infection. Roche is an ideal partner for Maxygen's next-generation interferon alpha and we are encouraged by their enthusiasm and commitment to the program."

Posted by Editors at 09:48 AM --- Printer-friendly version | Comments (0)

November 08, 2006

Hepatitis C Cleared in Some Drug Users

Although sharing contaminated needles for illicit drug use is the most common way of transmitting the Hepatitis C virus, many physicians are hesitant to administer treatment to active drug users. New research demonstrates how drug users are just as likely to clear the virus as non-drug users, which will likely change this prescribing trend and help reduce the spread of the disease.

Patients who recover from hepatitis C have lower risk of reinfection

A new study found that individuals who had tested positive for hepatitis C (HCV) but later tested negative for the virus were significantly less likely to become infected again compared to those who had never been infected, even though they had the same exposure risks.

The results of this study appear in the November 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).

HCV, a major public health threat affecting over 170 million people worldwide, is primarily acquired through injection drug use (IDU). IDU accounts for over 75 percent of HCV cases and HCV is seen in up to 90 percent of IDUs, with most of these individuals going on to develop chronic infection. Recent advances in effectively treating HCV have led to a "cure," (meaning no virus is detectable) in many cases, however there is a concern that treatment is not as beneficial to IDUs because they are continually exposed to the virus.

Through a collaborative effort between Jason Grebely and Brian Conway of the University of British Columbia, Mark Tyndall of the BC Centre for Excellence in HIV/AIDS, the BC Centre for Disease Control, and Vancouver Coastal Health in Vancouver, a large community-based study was conducted comparing 926 individuals who tested negative for HCV during the recruitment period of the study between January 2003 and June 2004 with 506 individuals who had HCV, 152 of whom had spontaneous clearance of the virus. Clearance was considered to be the presence of HCV antibodies followed by at least one negative test for HCV. Using medical records, they then looked at the incidence of HCV infection between 1992 and 2005 in those who had antibodies but no detectable virus and those who tested negative in order to evaluate the effect of previous infection on reinfection rates. Although the two groups were similar in terms of the proportion of individuals engaging in illicit drug use, those previously infected were more likely to be engaged in frequent illicit drug use and IDU. Individuals who had tested positive for HCV, but subsequently tested negative were followed for an average of five years, compared to almost three years for those without previous HCV infection.

The results showed that those with previous HCV infection and viral clearance were four times less likely to develop infection again than those infected for the first time, despite the fact that they had higher rates of HIV coinfection, illicit drug use and injection drug use. In fact, 90 percent of those reinfected continued to engage in illicit drug use, including 50 percent who reported IDU.

"Our data lend support to the hypothesis that previous exposure to HCV may be protective, possibly on an immunologic basis, despite repeated exposure to HCV," the authors state. They propose two potential explanations for their results: those with HCV clearance are genetically predisposed to resist HCV infection and reinfection, or those previously exposed to HCV may be more experienced and have safer injection routines, which would have some protective value. The authors acknowledge some limitations in their study, such as the fact that HCV antibody tests have become more sensitive in recent years compared to the period from which the study looked at results and the fact that the study was retrospective, with testing being performed only by physician request, not systematically. However, they note that these limitations could easily be addressed in future prospective studies with systematic testing for HCV.

The authors point out that treatment for HCV infection is often withheld from IDUs because of the supposed high risk of reinfection. "However, our data suggest that spontaneous clearance may confer some protection against re-infection," they write. "If protection against HCV infection extends to those who have cleared their viremia following antiviral therapy, it could provide a stronger rationale for expanding treatment programs for IDUs, including those who continue to be at risk for HCV exposure." Although further research is required, the present study indicates that since IDUs play such an important role in HCV transmission, strategies that address this group could have a significant impact on the HCV epidemic.
###

Source: "Hepatitis C Virus Reinfection in Injection Drug Users," Jason Grebely, Brian Conway, Jesse D. Raffa, Calvin Lai, Mel Krajden, Mark W. Tyndall, Hepatology; November 2006 (DOI: 10.1002/hep.21376).

Excerpt taken from public press release,Nov. 1
John Wiley & Sons, Inc.

Posted by Editors at 01:01 PM --- Printer-friendly version | Comments (0)