Research & Treatment News
December 27, 2006
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Anemia is a common side effect caused by the drugs used in Hepatitis C combination therapy. For affected individuals, researchers found that a red blood cell-boosting drug can increase tolerance for receiving full-strength Hepatitis C treatment.
Anemia Drug Helpful in Patients with Hepatitis C
December 27, 2006
paktribune.com
The hepatitis C virus can cause permanent liver damage, cancer, or even death. Early symptoms include fatigue, which can progress to the yellow staining of the skin called jaundice and swelling of the abdomen. People can get the virus through any exposure to infected blood, including intravenous drug use, body piercing, tattooing, unbandaged cuts or poorly sterilized medical equipment and blood transfusions.
Standard treatment for hepatitis C infection includes the immune system protein interferon alfa in combination with the antiviral agent ribavirin, both of which are associated with decreased hemoglobin levels, Dr. Douglas T. Dieterich and his associates note in The American Journal of Gastroenterology. When anemia results, ribavirin doses are usually reduced to levels that are likely to be less effective in controlling the hepatitis C virus.
Dieterich, from Mount Sinai School of Medicine, New York, and colleagues evaluated the efficacy of once-weekly doses of epoetin alfa in alleviating anemia and minimizing ribavirin dose reductions in 64 anemic, HCV-infected patients. After 16 weeks, patients assigned to epoetin alfa treatment had higher mean hemoglobin levels than did patients assigned to standard care, the authors report. Moreover, 83 percent of patients receiving epoetin alfa maintained daily ribavirin doses of 800 mg or more, compared with only 54 percent of patients receiving standard care.
Improvements in quality of life measures were greater in the epoetin alfa treatment group than in the standard care group, the investigators report, and epoetin alfa treatment was well tolerated.
"Based on the results of this study," the authors conclude, "epoetin alfa seems to be promising for the treatment of anemia in HCV-infected patients receiving ribavirin/interferon combination therapy. Further research is warranted to investigate the potential impact of epoetin alfa therapy on outcomes, including quality of life and sustained viral response."
Posted by Editors at 12:36 PM --- Printer-friendly version
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Encouraging results were just announced regarding the battle on liver cancer, a devastating illness that may follow Hepatitis C infection. Recently demonstrated to decrease liver tumor recurrence by 76 percent, Progen Industries' PI-88 will progress to Phase III clinical trials for liver cancer treatment.
Positive Results For Liver Cancer Trial
December 24, 2006
www.medicalnewstoday.com
Liver cancer (or hepatocellular cancer) is the fourth most common cancer in the world and one of the most deadly, killing most patients within a year. [1] In Australia in 2002 1.3% of all male deaths were due to liver disease in (AIHW National Morbidity Database, Australia's Health 2004, AIHW).
Most cases of liver cancer are caused by hepatitis infection (usually hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary liver cancer but metastasis (spread) of cancer from elsewhere in the body, e.g. the colon. Treatment options of liver cancer and prognosis are dependent on many factors but especially on tumor size and staging.
Progen Industries (ASX: PGL; Nasdaq: PGLA) today announced positive preliminary results from its Phase II clinical trial of PI-88 for the treatment of patients with primary liver cancer following surgical resection of the tumour. The trial demonstrated that PI-88 increased time to tumour recurrence by 76%.
The patient group treated with 160 mg of PI-88 had a substantial delay in tumour recurrence compared to those not receiving PI-88 (30 weeks compared with 17 weeks).
"These results are clinically very encouraging. It's hard to overstate the importance to the patient's quality of life of each day that they remain free of liver cancer. It is well known that once liver cancer recurs, the patient's survival prognosis is poor and the quality of life deteriorates dramatically," said Professor John Zalcberg, Chief Clinical Advisor to and Non-executive Director of Progen.
Justus Homburg, Chief Executive Officer of Progen stated, "We conducted this preliminary data analysis of all 168 evaluable patients at the 30-week time point to assist us now with a timely Phase 3 trial design. These results offer excellent support as we proceed to Phase 3 development, with the guidance of the FDA, as rapidly as possible. These 30-week data will not change and will be expanded upon as final 48 week data are analysed."
The final data for this Phase 2 trial (at 48 weeks -- comprising 36 weeks of treatment and a 12-week follow-up period) are expected to be available by the second quarter of 2007, once the final data from all trial sites have been checked, processed and statistically analysed. The trial is being conducted at six sites in Taiwan.
Progen is now preparing for much larger Phase III trial of PI-88 for the treatment of liver cancer which will include sites in the US, Taiwan, Singapore, China, Hong Kong and South Korea.
Dr. Chris Parish, PI-88 founding scientist from the Australian National University commented, "I am thrilled to see such strong clinical data on a product that I have spent many years studying. This demonstrates that the early discoveries we made in collaboration with Progen are now translating into benefits for cancer patients."
"The treatment of patients in a post-resection liver cancer setting is a very good match for the biological mechanism of action of PI-88. We know that even though the patient has surgery to remove the tumour there are still small tumours present. PI-88 works via a process called angiogenesis or the inhibition of growth of new blood vessels to these tumours and also on the spread of tumours, or metastatis. It is by this dual mechanism of action that we believe PI-88 has the potential to be any exciting alternative to current cancer treatments."
Posted by Editors at 12:21 PM --- Printer-friendly version
December 21, 2006
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A recent study has shown how HIV diminishes the immune system's ability to respond to Hepatitis C. Researchers from Massachusetts General Hospital indicate that co-infected individuals should begin anti-retroviral treatment earlier than those only infected with Hepatitis C.
Science Daily
December 18, 2006
Coinfection With Both HIV And Hepatitis C Virus A Growing Problem
Although many individuals infected with the hepatitis C virus (HCV) are naturally able to control levels of the virus with their immune systems, those who also become infected with HIV, the virus that causes AIDS, may lose that ability. In a report in the December issue of PLOS Medicine, a group of researchers from the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH) report one of the first studies of how HIV infection impacts immune system functions involved with HCV control. Their findings suggest that beginning antiretroviral therapy earlier than is generally recommended may help preserve HCV control in patients infected with both viruses.
"The global burden on health of chronic viral infections is immense, and HCV and HIV are chief among culprit viruses," says Arthur Kim, MD, of PARC-MGH, co-first author of the PLOS Medicine report. "Due to shared routes of transmission, infection with both viruses is common. Unfortunately, HCV behaves as an opportunistic infection in the presence of HIV and is becoming a leading cause of illness and death in persons with HIV."
In order to examine immune system factors associated with spontaneous control of HCV and how that control is altered by HIV infection, the researchers enrolled four groups of participants: 60 were infected with both viruses, and half of those had low HCV levels upon entering the study. The other two groups of 17 participants were infected with HCV only, with one group successfully controlling viral levels. Spontaneous HCV control is known to rely on the activity of CD4 helper T cells specifically targeted against the virus, and destruction of CD4 cells by HIV underlies the immune deficiency that characterizes AIDS. Therefore the researchers measured participants' T cell response to HCV at the outset of the study and at two- to six-month intervals during the study period.
The results showed that those individuals able to maintain low HCV levels in spite of HIV coinfection had stronger virus-specific responses for both CD4 T cells and the CD8 "killer" T cells than did those with elevated HCV counts. Not surprisingly, participants infected only with HCV had even more powerful antiviral T cell responses. About a quarter of those infected with both viruses who originally controlled HCV levels lost control during the two-and-a half-year study period, and their increased virus levels corresponded with an overall drop in CD4 T cells. None of the viral controllers who were infected with HCV alone had any increase in viral levels during the study period. Loss of protective responses and susceptibility to recurrent HCV infection may help to explain the higher rates of persistent HCV observed in subjects who are HIV/HCV coinfected, compared to those with HCV alone.
In analyzing factors that might be associated with the loss of HCV control in those infected with both viruses, the researchers made a surprising discovery. The factor most powerfully associated with maintaining HCV control was not the CD4 T cell count upon entering the study but the lowest previously recorded or 'nadir' CD4 count. That finding suggests that, for individuals infected with both viruses, beginning antiretroviral treatment before CD4 levels drop too low to maintain HCV responses may be desirable.
The researchers also found that, among those whose HCV levels rose, individuals who maintained some T cell responses had lower viral levels than did those with little or no T cell response. This suggests that the immune system retains a level of secondary immunity against HCV -- the kind of 'memory' response against a previously encountered pathogen seen in many infections.
"Currently a nationwide trial is recruiting people for a study examining whether earlier treatment of HIV will improve hepatitis C treatment outcomes," Kim says. "Part of this study will investigate how earlier treatment may affect immune responses. It also will be important to follow the impact of loss of HCV control on liver disease, since this will probably have important consequences for patients with HIV." Kim is an instructor in Medicine at Harvard Medical School.
Note: This story has been adapted from a news release issued by Massachusetts General Hospital.
Posted by Editors at 4:12 PM --- Printer-friendly version
December 12, 2006
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Pegylated interferon and ribavirin therapy non-responders are the focus of a Phase 4 study evaluating the safety and efficacy of Infergen® (consensus interferon) in combination with ribavirin.
Valeant Pharmaceuticals International (NYSE:VRX) today announced its plans to initiate a phase 4 study of Infergen(R) (Consensus Interferon), which is in development for daily use in combination with ribavirin in the treatment of hepatitis C in patients who were non-responsive to previous pegylated interferon and ribavirin therapy. The study will evaluate the use of Infergen 15 ug/day plus ribavirin (1.0-1.2 g/day) in patients who did not have an optimal response at week 12 of treatment with pegylated interferon and ribavirin.
"Approximately 50 percent of patients do not respond to initial pegylated interferon and ribavirin therapy. Week 12 has been shown to be a pivotal time point in determining the likelihood of responding to therapy. Patients who still have detectable virus at week 12 have less chance of sustaining an SVR than those who are undetectable at week 12. These patients are in need of a new treatment regimen to improve their chance at achieving a sustained response," commented Mitchell L. Shiffman, the study's principal investigator and Chief of Hepatology at Virginia Commonwealth University Medical Center.
The multi-center, randomized U.S. study will enroll patients who received initial treatment with pegylated interferon and ribavirin and achieve a greater than 2log10 decline in HCV RNA at week 12 but still have detectable virus. The patients will be immediately randomized to receive Infergen 15 ug/day plus ribavirin (1.0-1.2 g/day) for 36 or 48 weeks or continue on their pegylated interferon and ribavirin regimen for an additional 36 weeks of therapy. All treatment groups will have a 24 week follow up period to measure sustained virologic response.
"Based on interim results from the DIRECT trial, a shorter washout period from previous pegylated interferon and ribavirin therapy and the degree of fibrosis, may affect response to daily Infergen and ribavirin. This study is the next step in the development of Infergen in patients who exhibit a poor response to initial treatment with pegylated interferon and ribavirin," said Wesley P. Wheeler, Valeant's President of North America and Global Product Development.
Posted by Editors at 4:36 PM --- Printer-friendly version
December 11, 2006
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A Brazilian case study report indicates that by adding thalidomide to standard combination therapy, six HCV-positive, prior non-responders experienced total remission of their chronic Hepatitis C. Known to cause severe congenital abnormalities, thalidomide's safety and efficacy must be investigated in future Hepatitis C trials before being considered as a viable treatment.
Report of 6 Cases of Complete HCV Remission in Prior Non-Responders Treated with Pegylated Interferon Plus Ribavirin Plus Thalidomide
By Ronald Baker, PhD
Excerpt taken from www.hivandhepatitis.com
Although it represents the current standard of care for chronic hepatitis C virus (HCV) infection, combination therapy with pegylated interferon plus ribavirin does not provide optimal treatment for this debilitating and life-threatening disease, which impacts a significant portion of the world's population.
The present article reviews a recent Brazilian paper published in Revista do Instituto de Medicina Tropical de Sao Paulo. This report describes 6 chronic HCV patients who failed initial combination therapy with pegylated interferon/ribavirin (Peg-IFN/RBV). After the addition of thalidomide to Peg-IFN/RBV therapy, all 6 experienced complete remission of their chronic hepatitis C infection and presented with negative HCV RNA, according to the author of these case reports.
The use of thalidomide in a triple combination regimen with pegylated interferon and ribavirin for the treatment of hepatitis C is described in these Brazilian case reports for the first time in the medical literature.
Source:
M M Caseiro. Treatment of chronic hepatitis C in non-responsive patients with pegylated interferon associated with ribavirin and thalidomide: report of six cases of total remission. Revista do Instituto de Medicina Tropical de Sao Paulo 48(2): 109-112. April 2006.
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December 7, 2006
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DNA vaccines are the next wave of hope in disease prevention. Scheduled to make its clinical trial debut in early 2007, Inovio's proprietary electroporation DNA delivery system is designed to activate a T-cell response capable of clearing HCV.
Inovio Biomedical Partner Tripep Files Application for Phase I Clinical Study of Hepatitis C DNA Vaccine
Tuesday, December 5th
SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB of Sweden, has filed an application for a phase I clinical study with the Swedish Medical Products Agency. The application is designed to permit initial clinical testing of Tripep’s proprietary DNA vaccine, ChronVac-C®, administered using Inovio’s MedPulser® DNA Delivery System. This combination is designed to activate a T-cell response capable of clearing hepatitis C virus. Tripep intends to conduct a phase I clinical study in healthy volunteers at the Center for Gastroenterology at Karolinska University Hospital in Sweden beginning in early 2007.
“Our partnership with Tripep has rapidly moved this vaccine from concept to initial clinical evaluation in less than a year,” stated Avtar Dhillon, MD, Inovio’s president and CEO. “This vaccine trial represents the first study in man of an infectious disease vaccine delivered with electroporation and we are excited about the product’s potential.”
About Inovio’s DNA Delivery Technology
DNA vaccines have the potential to by-pass the numerous problems that plague conventional vaccines. For example, DNA vaccines may be better in stimulating cellular immunity necessary to fight chronic infection or diseases such as cancer. Despite this promise, vaccination using DNA plasmids alone, without enhanced delivery, has not been shown to reach the threshold for clinical benefit.
Intramuscular delivery of DNA vaccines using Inovio’s proprietary electroporation technology has been shown in primate studies to boost the immune response by orders of magnitude over DNA plasmid alone. Plasmid-based vaccines induced higher levels of antibodies and T-cell responses when delivered via electroporation, suggesting the potential to provide better protection from infectious diseases such as HIV and hepatitis C.
ChronVac-C(R) is designed to be a therapeutic DNA vaccine that can stimulate the body’s immune system. Animal experiments have demonstrated that ChronVac-C vaccination activated B-cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid will be injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio’s electroporation-based DNA delivery system. These muscle cells would be expected to then produce predetermined proteins that may activate the body’s immune system to attack all cells producing HCV proteins.
Source: Inovio Biomedical Corporation
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