Research & Treatment News
April 30, 2008
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A Phase IIa trial investigating triple combination therapy with PEGASYS, COPEGUS and Roche's investigational drug R1626, demonstrated a higher response rate than traditional combination therapy alone. While R1626's effectiveness and high barrier to resistance makes it a top Hepatitis C contender, the following six months will determine if its ability to clear the virus lasts.
Roche's Investigational Hepatitis C Polymerase Inhibitor, R1626, Demonstrated Significant End-of-Treatment Response In Phase IIa Study
www.medicalnewstoday.com
Article Date: 27 Apr 2008
Roche's investigational therapy for chronic hepatitis C virus (HCV) infection, R1626, has shown a significant end-of-treatment response rate when given in combination with PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). R1626 also shows a high barrier to the development of resistance.
After four weeks of treatment with this triple combination, followed by 44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84 percent of patients infected with genotype 1 virus. This was higher than patients treated with PEGASYS and COPEGUS alone for the entire 48-week treatment period (65 percent). These new data were presented in a late-breaker oral session at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), being held in Milan, Italy.
R1626 was discovered and developed at Roche and belongs to a class of antivirals called polymerase inhibitors, which are being investigated with the current standard of care for hepatitis C combination therapy with pegylated interferon and ribavirin.
"These results demonstrate that R1626 holds significant promise to potentially increase the number of hepatitis C patients who can be successfully treated," said Dr. David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, Florida. "Since most patients responded very early in treatment with R1626, we expect sustained virological response (SVR) rates that improve significantly on those achieved with the current standard of care. I look forward to SVR data from this Phase IIa study, and to results of the ongoing Phase IIb study."
Patients in this Phase IIa study will be followed for an additional 24 weeks with no treatment to determine the SVR rate, which indicates successful treatment.
More About the Phase IIa Study and End-of-Treatment Results
The Phase IIa study is a multicenter trial that enrolled 104 patients with genotype 1 HCV, who had not previously received treatment. Its primary endpoint was to evaluate the four-week efficacy and safety of combining R1626 with PEGASYS alone or with PEGASYS plus COPEGUS, in comparison to a current HCV standard of care (SOC), pegylated interferon plus ribavirin.
Patients were randomized into the following treatment groups:
-- Group A: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly for four weeks
-- Group B: R1626 3,000 mg twice a day plus PEGASYS 180 mcg weekly for four weeks
-- Group C: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks
-- Group D (standard of care group): PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks
Following the four weeks of treatment in this study, all patients received PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for an additional 44 weeks to complete the 48-week trial.
The study found:
-- Data collected at four weeks showed that patients receiving the triple combination (Group C) had a mean decrease in viral load of 5.2 log10 from baseline, indicating a robust and rapid virological response.
-- At week 48, HCV was undetectable in 84 percent of patients (26 of 31) who received the triple combination of R1626 1,500 mg BID + PEGASYS + COPEGUS compared with 65 percent of patients (13 of 20) treated with the SOC.
-- A higher incidence of grade four neutropenia was reported in the R1626 treatment arms during the four-week treatment period; however, after stopping treatment with R1626, absolute neutrophil counts returned to the level typically seen with patients receiving the SOC alone.
R1626 - A High Barrier to the Development of Resistance
In a separate oral presentation at EASL, it was reported that R1626 continues to present a high barrier to the development of viral resistance. This is a serious concern emerging in the development of small molecule treatments for hepatitis C. Resistance to R1626 has not been yet been identified, after either two weeks of R1626 monotherapy, or after four weeks in patients treated with R1626 in combination therapy.
Rapid Development of R1626 - A Large Phase IIb Study is Now Fully Enrolled
A large Phase IIb study with R1626 was initiated in November 2007 to define the optimal dose of R1626, in combination with PEGASYS and COPEGUS. This Phase IIb trial, called POLI 1, is now fully enrolled with approximately 500 patients, all with genotype 1 hepatitis C.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and a leading cause of cirrhosis, liver cancer and the need for liver transplants. According to the Centers for Disease Control and Prevention (CDC), an estimated 4.1 million Americans (1.6 percent) have been infected with hepatitis C; 3.2 million are chronically infected. The number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. CDC estimates the number of hepatitis C-related deaths could increase to 38,000 annually by the year 2010, surpassing annual HIV/AIDS deaths.
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.
IMPORTANT SAFETY INFORMATION
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS(R) (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS(R), may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).
Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema). Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at http://www.RocheExchange.com.
All trademarks used or mentioned in this release are protected by law.
Roche
http://www.rocheusa.com
Posted by Editors at 2:26 PM --- Printer-friendly version
April 29, 2008
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A four-year study confirms that low-dosage maintenance interferon therapy prevents disease progression in those with portal hypertension or cirrhosis from Hepatitis C.
Positive Findings In Treating Patients With Advanced Hepatitis C, Study Shows
www.sciencedaily.com
ScienceDaily (Apr. 25, 2008) — The hepatitis C therapy peginterferon alfa-2b, when given as low-dose maintenance therapy, can prevent disease progression in certain patients who failed previous interferon-based hepatitis C therapies and have advanced liver disease, according to findings from a large, four-year study presented April 24 at the 43rd annual meeting of the European Association for the Study of the Liver (EASL).
The study, called COPILOT (COlchicine versus Peg-Intron LOng-Term), showed that low-dose peginterferon alfa-2b was superior to colchicine in improving the disease-free survival of patients with cirrhosis and portal hypertension, especially in patients who stayed on treatment. In the study, more than 40 percent of patients had portal hypertension, a condition of high blood pressure in the major vessel going to the liver from the gastrointestinal tract and which often accompanies liver cirrhosis. However, peginterferon alfa-2b maintenance therapy was not superior to colchicine in patients overall.
"These findings make a strong case for considering low-dose peginterferon alfa-2b as a maintenance therapy in patients with cirrhosis and portal hypertension who have failed hepatitis C eradication therapy," said principal investigator Nezam Afdhal, M.D., Chief of Hepatology at Beth Israel Deaconess Medical Center (BIDMC) and Associate Professor of Medicine at Harvard Medical School. "While other interferon maintenance therapies have been studied in the past few years in previous interferon nonresponders, these findings show, for the first time, a clinical benefit in a specific population with advanced disease," he said.
Hepatitis C virus (HCV) infection is transmitted through exposure to infected blood and affects an estimated 4 million individuals in the United States. The current standard treatment, combination therapy with pegylated interferon plus ribavirin for 24 to 48 weeks, can eradicate the virus in about 50 percent of patients. Those who do not respond and have cirrhosis are at far greater risk for developing liver cancer or liver failure, so the development of treatment strategies for these nonresponders is a priority.
Conducted at approximately 40 sites in the United States, the COPILOT study compared weight-based low-dose peginterferon alfa-2b (subcutaneous injection of 0.5 mcg/kg/wk, one-third the dose used in standard HCV combination therapy) versus colchicine (0.6 mg orally, twice daily), an anti-inflammatory and antifibrotic medication, in 555 chronic hepatitis C patients with advanced liver fibrosis who previously failed interferon-based therapies. Patient baseline characteristics were well balanced between the two study arms.
Over the four years of the randomized study, investigators monitored the patients to determine how many reached a primary endpoint, defined as death, liver transplant, hepatocellular carcinoma (liver cancer), variceal bleeding, or liver failure (increase in Child-Pugh-Turcotte [CPT] by 2 points with ascites, jaundice or encephalopathy). They analyzed their findings for all 555 patients, who received at least one dose of their assigned drug, in two ways: based on all events that occurred during the entire four years of the study, regardless of whether a patient was still taking their assigned drug or not (the "intent-to-treat" or ITT analysis), and based on only the events that occurred while patients were taking their assigned drug (the "on drug" analysis).
The investigators found a primary endpoint was reached by 17.8% (51/286) of patients in the peginterferon alfa-2b group versus 20.4% (55/269) in the colchicine group in the ITT analysis, and by 12.2% (35/286) and 16.0% (43/269) patients, respectively, in the on-drug analysis (treatment differences were not statistically significant). Among patients who had portal hypertension (42.3% and 48.0% of patients in the peginterferon alfa-2b and colchicine groups, respectively), peginterferon alfa-2b therapy resulted in significantly improved event-free survival in both the ITT and on-drug analyses (Wilcoxon p = 0.041 and 0.028, respectively). Further, variceal bleeding, a specific complication of portal hypertension, was almost abolished with peginterferon alfa-2b in both the ITT (10 vs. 1 patients) and the on-drug (10 vs. 0 patients) analyses. In the ITT analysis, hepatocellular carcinoma occurred in 7.7% and 5.9% of patients in the peginterferon alfa-2b and colchicine groups, respectively, a non-significant difference.
Overall, 49% of patients discontinued their medication before the end of the four-year study, with 36% due to failure to comply and 13% due to side effects. Peginterferon alfa-2b was generally well tolerated. Among patients who discontinued due to interferon side effects (17.1%, 49/286), the most common reason (45%, 22/49 patients) was general intolerance to interferon (e.g., due to flu-like symptoms, malaise, and other common interferon side effects).
The COPILOT study was supported by Schering-Plough Corporation, manufacturer of peginterferon alfa-2b.
Adapted from materials provided by Beth Israel Deaconess Medical Center, via EurekAlert!, a service of AAAS.
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Currently approved for treating contagious diarrhea in children, nitazoxanide has been found to make pegylated interferon-based treatment for Hepatitis C genotype 4 more effective. Prompting new trials in the U.S. and Europe, this drug is now being evaluated for Hepatitis C genotype 1.
Nitazoxanide Demonstrates Activity in Treatment-Naive Patients With Hepatitis C Virus Genotype 4: Presented at EASL
By Emma Hitt, PhD
www.docguide.com
MILAN, Italy -- April 29, 2008 -- Nitazoxanide significantly improves response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic hepatitis C virus genotype 4 (HCV-4), according to new research findings presented here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).
Jean-Francois Rossignol, MD, Research Scientist, and Cofounder, Romark Institute For Medical Research, Tampa, Florida, reported the results of a randomised trial of nitazoxanide, an oral agent that targets host-cell interactions with HCV. Dr. Rossignol and colleagues sought to evaluate the antiviral activity and safety of nitazoxanide in combination with PEG-IFN alfa-2a, with or without ribavirin.
A total of 120 patients with chronic HCV-4 were sequentially randomised to 1 of 3 treatment arms. The first arm was a standard-of-care arm: PEG-IFN alfa-2a plus ribavirin (RBV) for 48 weeks. The second arm was nitazoxanide for 12 weeks followed by nitazoxanide plus PEG-IFN alfa-2a for 36 weeks. The third arm was a triple therapy consisting of nitazoxanide for 12 weeks followed by nitazoxanide combined with PEG-IFN alfa-2a plus RBV for 36 weeks.
PEG-IFN alfa-2a was injected by clinical investigators at 180 mcg/kg/week while ribavirin was dosed at 1000 to 1200 mg/day. Nitazoxanide was administered at 500 mg twice daily with food.
Patients were previously untreated, with the exception of 12 interferon-experienced patients included in each of the nitazoxanide-containing arms.
During the monotherapy lead-in phase with nitazoxanide, a modest (0.25 log10) but statistically significant decrease in HCV ribonucleic acid (RNA) from baseline to week 12 was observed (P = .0032). Out of 76 patients, 5 had a drop in HCV RNA of greater than 1 log10 from baseline to week 12; and 1 patient had undetectable HCV RNA, with a 5.4 log10 decline in HCV RNA and normalised alanine aminotransferase (ALT) test results at week 12. There was no significant change in overall ALT measurements during the lead-in period.
Among the interferon-naive patients (n = 96), the patients receiving the triple regimen (nitazoxanide plus PEG-IFN plus RBV) achieved a higher sustained viral response (SVR) than the patients receiving the standard of care (79% vs 50%; P = .023). In the nitazoxanide arm without RBV, the SVR was 61%. The rapid viral response (RVR) was also higher in patients receiving the triple therapy compared with those receiving the standard of care (64% vs 38%; P = .048).
In the interferon-experienced patients (n = 24), no efficacy differences were observed between the 2 nitazoxanide-containing arms (not compared with standard of care).
"Adverse events in the overall population were characteristic of those typically observed with pegylated interferon and ribavirin, with no additional effects resulting from nitazoxanide," Dr. Rossignol noted here on April 25. "Additional clinical trials of nitazoxanide in interferon-naive patients and nonresponders to pegylated interferon plus ribavirin have been initiated in patients with HCV genotype 1 in the United States and Europe."
Nitazoxanide was initially developed as an antiprotozoal, antiviral, and antibacterial agent, and is approved for the treatment of diarrhoea caused by Cryptosporidium and Giardia in children. Nitazoxanide has since shown activity against HCV and hepatitis B virus.
[Presentation title: Randomized Controlled Trial of Nitazoxanide-Peginterferon-Ribavirin, Nitazoxanide-Peginterferon and Peginterferon-Ribavirin in the Treatment of Patients With Chronic Hepatitis C Genotype 4. Abstract 68]
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April 28, 2008
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New research was presented at the American Association for Cancer Research supporting the use of Lapatinib for those with advanced liver cancer. Although currently approved for treating breast cancer, this drug represents hope for those who have progressed from chronic Hepatitis C to hepatocellular carcinoma.
Lapatinib Shows Promise for Advanced Hepatocellular Carcinoma: Presented at AACR
www.docguide.com
By Sophie Bainbridge
SAN DIEGO -- April 21, 2008 -- Lapatinib, a kinase inhibitor recently approved in the United States for treatment of HER2-positive metastatic breast cancer, may also be effective in patients with advanced hepatocellular carcinoma (HCC), investigators reported here at the American Association for Cancer Research (AACR) Annual Meeting 2008.
In a phase 2 trial that included 26 patients with advanced HCC, treatment with lapatinib stabilised disease in 8 patients after a median of 2 treatment cycles, and disease stabilisation lasted longer than 6 months in 8% of these patients, said Joseph Markowitz, MD, PhD, Researcher, Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
"Rates of liver cancer are increasing in the United States. This rise correlates with the increase in hepatitis-C-related liver disease, which is a principal risk factor for HCC," Dr. Markowitz said in a poster presentation on April 15. "There is also a link to an increased incidence of fatty liver, which is more prevalent these days because of the increasing rates of obesity and type 2 diabetes in the US population."
Lapatinib blocks the activity of the tyrosine kinase enzyme of both epidermal growth factor receptor (EGFR) and HER2/neu, and should be effective in patients who express one or both receptors.
"Given the lack of curative or even modestly effective treatment options for patients with advanced hepatocellular cancer, new therapies are desperately needed," he said.
Dr. Markowitz and principal investigator Tanios Bekaii-Saab, MD, Assistant Professor, Hematology and Oncology, and Assistant Professor of Pharmacology, also at Ohio State University, treated patients with oral lapatinib 1,500 mg/day. Each treatment cycle consisted of 28 consecutive days, and the median number of cycles was 2, with some patients receiving only one 1 cycle and some receiving as many as 12 cycles.
Patients had a median age of 58 years (range, 29-83 years), 65.4% were men, and Eastern Cooperative Oncology Group performance status was 0 in 12 patients and 1 in 14 patients. Twenty percent of patients had been on previous treatment before receiving lapatinib.
Patients underwent radiological assessments every 8 weeks.
Although there were no objective responses, 31% of the patients achieved disease stabilisation, and 8% had stable disease lasting longer than 6 months, Dr. Markowitz reported.
The most common toxicities were diarrhoea (69%) and nausea (54%). Three patients had grade 3/4 toxicities, including diarrhoea, rash, and acute renal failure. There was no evidence of cardiac dysfunction.
"We are analysing the survival data and correlative studies are underway to try to understand the molecular biology of this tumour and guide directed therapy for subsets of patients with hepatocellular carcinoma who may benefit from EGFR inhibition," Dr. Markowitz said.
He added that they are also studying K-RAS mutational status because it is thought that K-RAS mutations correlate with resistance to EGFR-directed treatment. "Knowing which patients have the mutation should help us tailor treatment," he commented.
[Presentation title: A Phase II Study of The Efficacy and Tolerability of Lapatinib in Patients With Advanced Hepatocellular Carcinomas. Abstract LB-306]
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April 18, 2008
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Researchers from Oklahoma have revealed that a drug commonly prescribed for high cholesterol also lowers Hepatitis C viral load. Although not capable of clearing Hepatitis C on its own, a Phase II trial will reveal its effectiveness in combination with interferon and ribavirin.
Researchers Find New Treatment for Hepatitis C
www.physorg.com
April 11, 2008
Researchers at the Oklahoma University Health Sciences Center have found a new use for an old drug. Their findings appear online in the American Journal of Gastroenterology.
The drug, Fluvastatin, has been approved since 1993 by the U.S. Food and Drug Administration for the treatment of elevated cholesterol in adults. Millions of patients have taken Fluvastatin for cholesterol without difficulty.
In a study of 31 veterans at the Veteran’s Administration Medical Center in Oklahoma City, researchers found that Fluvastatin significantly lowered the viral load, or levels of hepatitis C virus, for up to six weeks when used alone.
“This research is the first to demonstrate the antiviral activity of Fluvastatin in human beings infected with hepatitis C, most of whom were non-responders to the standard of care treatment,” said Ted Bader, M.D., the principle investigator on the project and director of liver diseases at the OU Health Sciences Center.
Since Fluvastatin will not completely clear the hepatitis C virus by itself, researchers have started a phase II randomized, controlled trial that combines Fluvastatin with the standard treatment of peg-interferon and ribavirin. They hope to use the combination of medicines to significantly improve the cure rate for hepatitis C. After further required testing and approval, the drug could be available as a new treatment for hepatitis C far sooner than any other anti-hepatitis C drug currently under research and development.
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Due to phase II safety trial results, Wyeth Pharmaceuticals and ViroPharma Inc. agreed to discontinue developing their Hepatitis C drug HCV-796. Executives report that HCV-796's capacity to inflict liver damage was too great to maintain its candidacy.
ViroPharma, Wyeth end development of hepatitis C drug
Philadelphia Business Journal
www.bizjournals.com
Thursday, April 17, 2008
ViroPharma Inc. and Wyeth Pharmaceuticals have decided to discontinue the development of HCV-796, their new drug candidate being developed as a potential treatment for hepatitis C.
The companies said Wednesday night the decision was based on a previously announced safety issue -- an increased risk of liver damage -- that emerged during phase-II testing of the compound.
"Clearly, this is a disappointing outcome for patients suffering from this difficult disease," said Vincent Milano, president and CEO of ViroPharma (NASDAQ:VPHM) of Exton, Pa. "Significant activities were undertaken to determine a clear path forward for HCV-796; however, the risk associated with potential hepatotoxicity ultimately posed too high of a hurdle to merit further development."
ViroPharma and Wyeth Pharmaceuticals of Collegeville, Pa., a division of Madison, N.J.-based Wyeth (NYSE:WYE), said they do not expect to continue to collaborate on future development of hepatitis C treatment candidates.
Posted by Editors at 10:13 AM --- Printer-friendly version
April 17, 2008
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The warmer weather is here and so are those pesky flies and insects. Learn if you should be worried about being infected with viral hepatitis from insect bites.
by Nicole Cutler, L.Ac.
Regardless of how technologically advanced a culture is, the viral hepatitis epidemic seems to be enveloping the globe. Of particular concern to the healthcare community, the viruses that cause chronic hepatitis are the most troublesome. Chronic infection with Hepatitis B or Hepatitis C can progress to advanced liver disease, a fate involving cirrhosis, liver cancer or liver failure. A vehicle for transmitting some types of viruses, some people worry that an insect bite could pass on viral hepatitis. Since many cases of chronic viral hepatitis are incurable, hepatitis prevention takes center stage. However, even the most prepared have trouble preventing insect bites.
Because scientists know that Hepatitis B and Hepatitis C are primarily spread via blood- to-blood contact, all possible breaches of the skin have been suspected in viral hepatitis transmission. Occurring when blood from an infected person enters the body of a person who is not infected, Hepatitis B and Hepatitis C are mostly spread through:
· having unprotected sex with an infected person (more likely with Hepatitis B)
· sharing drugs, needles, or “works” when injecting drugs
· needle sticks or sharp exposures on the job
· from an infected mother to her baby during birth
· being tattooed with a contaminated needle (more likely with Hepatitis C)
Hepatitis B Virus (HBV) Transmission Risks
According to the Centers for Disease Control (CDC), those at highest risk for Hepatitis B infection include:
· Persons with multiple sex partners or diagnosis of a sexually transmitted disease
· Men who have sex with men
· Sex contacts of infected persons
· Injection drug users
· Household contacts of chronically infected persons
· Infants born to infected mothers
· Infants/children of immigrants from areas with high rates of Hepatitis B infection
· Healthcare and public safety workers with exposure to blood
· Hemodialysis patients
Hepatitis C Virus (HCV) Transmission Risks
According to the CDC, those at highest risk for Hepatitis C infection include:
· Injection drug users
· Recipients of clotting factors made before 1987
· Hemodialysis patients
· Recipients of blood and/or solid organs before 1992
· People with undiagnosed liver problems
· Infants born to infected mothers
· Healthcare/public safety workers – Low risk
· People having sex with multiple partners – Low risk
· People having sex with an infected steady partner – Low risk
Mosquito Transmission
Aside from the characteristic itching and swelling involved, fears of mosquito bites spreading disease are due to its contact with blood. The insect pierces the skin, siphons out a person’s blood then repeats on a different individual – all without sterilization in between victims. Although some say there is a theoretical risk of being infected with viral hepatitis from a mosquito bite, there are no known cases worldwide. If mosquito transmission of Hepatitis B or Hepatitis C were possible, many more millions of people would likely be affected. However, mosquito bites can transmit some viruses. Mosquito-born diseases include:
· Encephalitis
· Malaria
· Dengue fever
· Rift Valley fever
· Yellow fever
Bed Bug Transmission
Similar to a mosquito’s motive, bed bugs are also bloodsuckers. Bed bug bites can create considerable anxiety and localized and occasionally systemic reactions. Different from mosquitoes, bed bugs may be a suspected transmitter of viral hepatitis:
1. HBV – Hepatitis B viral DNA can be detected in bed bugs up to six weeks after they feed on infectious blood, but no transmission of Hepatitis B infection was found in a chimpanzee model.
2. HCV – Transmission of Hepatitis C is unlikely, since Hepatitis C viral RNA is not detectable in bed bugs after an infectious blood meal.
Regardless of the presence or absence of genetic material, these critters have never been proven to transmit disease. However, if concerned about the potential for getting Hepatitis B from this insect, make sure you are vaccinated. Some suggestions for detecting bed bugs include:
· Look around. Bed bugs are large enough to see.
· Look under the mattress and in the seams, in and around the bed frame and along any cracks or peeling paint in the wall or picture frames.
· Check in the cracks of any wooden furniture, particularly antiques.
· You can also spot bed bugs’ droppings, which may be tinged with blood.
Although the thought of mosquito or bed bug bites may be disconcerting, we do share this planet with them. Without invitation, these bugs break our skin and extract our blood, actions which logically cause concern. Thankfully, the risk of being infected with HBV or HCV through insect bites is just shy of impossible. So using mosquito repellant and checking for bed bugs will make you more comfortable and spare some itching, but it won’t make a difference in your susceptibility to acquiring viral hepatitis.
References:
Hwang, W. Stephen, et al., Bed Bug Infestations in an Urban Environment, Emerging Infectious Diseases, April 2005.
http://hotels.about.com, Bed Bugs, Charlyn Keating Chisholm, About.com, 2007.
www.cdc.gov, Hepatitis B: Fact Sheet, Centers for Disease Control, 2007.
www.cdc.gov, Hepatitis C: Fact Sheet, Centers for Disease Control, 2007.
www.emedicine.com, Bedbug Bites, Robert A Schwartz, MD, MPH, WebMD, 2007.
www.hepatitisc.org.uk, FAQ, Glasgow and Scotland Hepatitis C Charity, 2007.
www.whfhhc.com, Can Hepatitis B be transmitted by a mosquito or insect bite?, Centers for Disease Control, 2007.
Posted by Editors at 4:04 PM --- Printer-friendly version
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Even though you may be on a first name basis with your general practitioner, research from Germany proves that your chances for successfully eliminating the Hepatitis C virus are greater when treated by a hepatologist.
by Nicole Cutler, L.Ac.
Once diagnosed with Hepatitis C, a little research will eventually reveal that the current standard treatment is pegylated interferon with ribavirin. Despite the relatively low rate of success in eliminating the virus, many may mistakenly believe that it doesn’t matter who administers the treatment. However, new research demonstrates that it is well worth the effort to seek out a specialist for monitoring your therapy.
Successful Treatment
Known as sustained virological response (SVR), successful treatment for Hepatitis C is described as the inability to detect any of the virus in the blood six months after stopping therapy. Although it is currently the only viable option for Hepatitis C, estimates of those attaining SVR with pegylated interferon and ribavirin treatment vary widely.
Regardless of a study’s country of origin, large trials evaluating Hepatitis C treatment success have reported SVR rates ranging between 30 and 80 percent. However, close examination of people fighting Hepatitis C in the real world have led researchers to suspect that the type of doctor a patient seeks help from significantly impacts SVR likelihood.
German Study
In an attempt to realize the real world impact of the type of physician administering Hepatitis C treatment, researchers at the University of Dusseldorf conducted a landmark retrospective study. At their outpatient clinics, these German researchers analyzed the records of patients receiving at least one dose of interferon treatment for Hepatitis C over a span of seven years.
After analyzing over 300 people receiving Hepatitis C treatment for the first time, approximately two thirds consulted with an expert hepatologist on a regular basis while just over one third had their interferon treatment administered and supervised by a general practitioner. Even though the characteristics of infection were similar between those working with a hepatologist and those seeing a general practitioner, the outcomes of Hepatitis C treatment were significantly different between the two groups.
Right after interferon treatment, elimination of the Hepatitis C virus was more likely for those seeing a hepatologist:
· A viral load of zero was evident in 74 percent of those seeing a hepatologist.
· A viral load of zero was evident in 48 percent of those seeing a general practitioner.
At the six-month mark when SVR is measured, those seeing a hepatologist continued to have a definite advantage:
· SVR was attained by 66 percent of those seeing a hepatologist.
· SVR was attained by 34 percent of those seeing a general practitioner.
When broken down even more, those with genotypes 1 and 4 and those with advanced liver damage specifically benefited from expert care:
· For study participants infected with genotype 1 or 4, SVR was attained by 61 percent of those seeing a hepatologist.
· For study participants infected with genotype 1 or 4, SVR was attained by 27 percent of those seeing a general practitioner.
· For study participants with advanced liver damage, SVR was attained by 69 percent of those seeing a hepatologist.
· For study participants with advanced liver damage, SVR was attained by 25 percent of those seeing a general practitioner.
These results led the German authors to conclude “Patients with…genotypes 1 and 4 or with advanced liver damage benefit from HCV therapy supervision by a specialist, probably because of less frequent treatment interruptions or dose reductions.”
What Is An Expert?
A hepatologist is a physician who has obtained additional, specialized training in liver diseases. Initially, all hepatologists are trained in general internal medicine (adult medicine) or pediatrics (children’s medicine). Some pursue additional training in gastroenterology (which includes digestive disorders involving the esophagus, stomach, small and large intestines, pancreas, gallbladder and liver). However, to be a hepatologist, a fellowship focusing solely on the liver is typically mandated. Even though a hepatologist is the most qualified type of doctor to treat liver disease, there is currently no separate board certification examination in this highly specialized field.
The field of hepatology is a rapidly changing, emerging field. Even though the standard of care for Hepatitis C has been interferon-based treatment for many years, there are many factors involved in its administration. Hepatologists are up-to-date on the latest research and discoveries for treatment modifications, length of treatment, dosage adjustments, side effect management and all of the other details related to Hepatitis C treatment.
Although most people are comfortable with their general practitioner – and they may have been the physician who originally detected their infection – an expert may be more qualified to administer Hepatitis C treatment. Especially important for people who have genotypes 1 or 4, or who already have advanced liver disease, the chance of achieving SVR is much higher when an expert liver specialist manages treatment.
References:
http://depts.washington.edu, Sagir, A., et al., Therapy outcome in patients with chronic hepatitis C: role of therapy supervision by expert hepatologists, Journal of Viral Hepatitis, September 2007.
www.acponline.org, Hepatitis C, American College of Physicians, ACP Observer, April 2006.
www.annals.org, Update in Hepatology, Willis C. Maddrey, MD, Annals of Internal Medicine, February 2001.
www.hepatitiscounselor.com, Thoughts about Hepatitis C and Liver Disease, Hepatitiscounselor.com, 2007.
www.hepato-site.net, What is a hepatologist and why do I need one?, University of Cincinnati, 2007.
www.hivandhepatitis.com, Treatment Outcomes in HCV Patients Whose Therapy is Supervised by Expert Hepatologists, hivandhepatitis.com, October 2007.
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April 7, 2008
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Of special interest for those who have relapsed after Hepatitis C pegylated interferon therapy: Medical experts are gaining insight into why some courses of treatment are unsuccessful. By aiming to eliminate the likely causes for previous failures, more non-responders may be good candidates for re-treatment.
by Nicole Cutler, L.Ac.
In the United States, the Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. Accounting for about 15 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis and up to 50 percent of cirrhosis, end-stage liver disease and liver cancer, HCV is a major threat to the health of our population. While it has undergone many improvements over the past decade, the current standard of therapy for HCV has a far way to go before this virus can be considered curable. Understanding why those with chronic HCV may not respond to treatment outlines the potential for successful re-treatment.
Sustained Virologic Response
The most common way to measure HCV treatment success is via the virologic response. To measure virologic response, doctors use a blood test to measure how much virus is in the blood. While Hepatitis C RNA may be undetectable immediately following treatment, this test must be repeated six months later to see if any of the virus remained and reproduced. Also referred to as viral load, the best outcome is a sustained virologic response (SVR). When the virus remains undetectable in the blood six months (or more) following HCV therapy, SVR is considered attained. So far, studies following those with HCV for two to three years after SVR have demonstrated a low relapse rate.
While the virologic response is primarily dependent on the action of the pegylated interferon, the prevention of relapse is mostly reflective of the action of ribavirin and the maintenance of its dosing. However, relapse prevention is also affected by the following variables:
· How quickly undetectable HCV RNA is attained after the start of treatment.
· How long the patient remains on treatment after achieving undetectable HCV RNA.
Broken down by the most common HCV genotypes, the following are estimates of how frequently SVR is attained with pegylated interferon and ribavirin therapy:
· Approximately 40 to 45 percent of those with chronic HCV genotype 1, the most common strain in the United States, achieve SVR.
· Approximately 75 to 80 percent of those with chronic HCV genotypes 2 and 3 achieve SVR.
Non-Responders
While those attaining SVR may be permanently free of HCV, the remaining people on pegylated interferon and ribavirin are non-responders. However, there is plenty of evidence that previous non-responders can be re-treated successfully, eventually achieving SVR. Identifying which HCV non-responders are appropriate candidates for re-treatment requires a complete understanding of the various virologic response patterns and the pitfalls associated with achieving and maintaining virologic response.
There are many reasons that a person may not achieve SVR. The individuals without any response to interferon-based therapies are poor candidates for re-treatment. These people have no significant decline in HCV RNA during treatment and are essentially immune to the effects of interferon. Aside from those without any virological response, the four most common reasons assumed responsible for continued HCV infection after treatment are missing doses, premature discontinuation of ribavirin, insufficient ribavirin dosage and infrequent viral load testing.
1. Missing a Dose – Recent studies highlight missing a dose of peg-interferon alfa and/or ribavirin as a leading contender for not achieving SVR. Missed doses can be a result of physicians instructing their patients to temporarily stop treatment because of significant treatment-related side effects, patients missing a dose by accident or intentional skipped doses in an attempt to self-treat side effects.
2. Premature Discontinuation of Ribavirin – Stopping ribavirin too soon increases the person’s chance of viral load rebound. In those who demonstrate a slow virologic response, several studies have demonstrated that relapse can be significantly reduced in those with HCV genotype 1 patients by prolonging the duration of treatment from 48 to 72 weeks.
3. Insufficient Ribavirin Dosing – Another frequently encountered reason for HCV relapse is initiating ribavirin treatment with an insufficient dosage. Three randomized trials have demonstrated that patients who initiate treatment with a higher dose of ribavirin have a lower relapse rate.
4. Infrequent Viral Load Testing – In addition, experts believe that SVR is attained by those who quickly recognize when viral load is undetectable and their current treatment regimen is adjusted swiftly. For this reason, viral load must be assessed periodically during treatment to identify this point as soon as possible.
By recognizing the patterns associated with a poor response to interferon-based therapy, physicians can better approximate why therapy failed and who might be a good candidate for re-treatment. If a non-responder attempts pegylated interferon and ribavirin treatment again, all efforts must be made to maintain adequate, sufficient dosing for the required time interval and frequently evaluate viral load. As long as there was some type of viral response to initial treatment, virologists estimate that a sizable percentage of previous non-responders are good candidates for HCV re-treatment.
References:
http://clinicaloptions.com, Understanding HCV Nonresponse and Identifying Candidates for Retreatment, Mitchell L. Shiffman, MD, Clinical Care Options LLC, 2008.
http://digestive.niddk.nih.gov, Chronic Hepatitis C: Current Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases, 2008.
Posted by Editors at 2:32 PM --- Printer-friendly version
April 4, 2008
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Scientists have discovered a unique property of a segment of one of Hepatitis C's proteins - inhibition of HIV. Continued research on this Hepatitis C component could lead to a new therapy capable of preventing HIV from being sexually transmitted.
Hepatitis May Be Ally Against HIV
April 1, 2008
www.sciam.com
A part of one of the proteins of the Hepatitis C virus shows anti-HIV activity in cell cultures. Cynthia Graber reports.
Podcast Transcript: The disease hepatitis C might provide a new tool in the fight against HIV/AIDS, say scientists at the Scripps Institute and in the Netherlands. The research was published March 31st online in the Proceedings of the National Academy of Sciences.
A segment of one of the proteins of the hepatitis C virus is called C5A. Ironically, this segment, or peptide, actually actually is deadly to the hepatitis virus. So scientists wondered if it could kill the HIV virus as well. They found that in cell cultures, C5A did indeed damage HIV. It also interfered with HIV’s ability to infect cells such as the immune system’s T cells. And C5A properties are in effect at low pH, which is important if any therapy based on it were to be used by women before sex.
The researchers say that C5A has a wider range of anti-viral activity than other antimicrobial peptides. Scientists hope that the Hep C peptide research will lead to the development of antiviral therapies that could help prevent the sexual transmission of HIV.
Posted by Editors at 3:47 PM --- Printer-friendly version
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In addition to demonstrating a Hepatitis C anti-viral effect, an early trial investigating ITMN-191 met safety goals. With this good news, a Phase II study will evaluate this drug in combination with pegylated interferon and ribavirin.
InterMune Hepatitis C Drug Passes Study
© 2008 The Associated Press
April 1, 2008, 9:48AM
www.chron.com
BRISBANE, Calif. — Biotechnology company InterMune Inc. said Tuesday its hepatitis C drug candidate met safety goals in an early stage clinical trial and showed signs of effectiveness.
The drug candidate ITMN-191, being developed with Swiss drug company Roche, reduced hepatitis C RNA in the small-scale study, showing an antiviral effect. Early stage clinical trials typically measure a drug's safety profile and whether it reaches its treatment target. The patient population is often too small to determine whether the drug candidate is actually effective.
The two companies plan a 14-day study on the drug in combination with two approved drugs, Pegasys and Copegus, also called ribavirin. An application was submitted to European regulatory authorities last month for the triple-combination study. Also, Roche has completed the tablet formulation of ITMN-191 and will use it in a midstage, or Phase II, clinical trial.
Shares of InterMune rose $2.84, or 19.1 percent, to $17.42. The stock has traded between $11.72 and $30.99 over the last 52 weeks.
Posted by Editors at 3:27 PM --- Printer-friendly version
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With a shocking 25 percent of Americans living with non-alcoholic fatty liver disease, California researchers claim that this condition is associated with a decline in cardiac and respiratory fitness levels.
1-in-4 U.S. Adults Have Fatty Liver Disease
www.redorbit.com
Tuesday, 25 March 2008, 12:00 CDT
One out of four U.S. adults suffers from non-alcoholic fatty liver disease — liver disease characterized by excessive fat in the liver, U.S. researchers said.
Non-alcoholic fatty liver disease, the most common cause of abnormal liver enzymes, is considered by many to be a manifestation of the metabolic syndrome — belly fat, elevated blood pressure, insulin resistance, high cholesterol — which result in an increased risk of coronary heart disease.
Study leader Joanne Krasnoff of the University of California San Francisco recruited 37 adult patients with a spectrum of non-alcoholic fatty liver disease severity measured by liver biopsy.
Patients had suboptimal cardiorespiratory fitness, muscle strength, body composition and physical activity participation. More than 97 percent had a body fat percentage that put them at increased risk for morbidity and mortality and less than 20 percent met recommended guidelines for physical activity.
The study, published in the April issue of Hepatology, demonstrated lower cardiorespiratory fitness in subjects with increasing non-alcoholic fatty liver disease severity.
However, the finding raised the question of a cause-or-effect phenomenon — does cardiorespiratory fitness attenuate non-alcoholic fatty liver disease, or does increasing non-alcoholic fatty liver disease severity result in a decline in cardiorespiratory fitness? the authors asked.
Posted by Editors at 2:15 PM --- Printer-friendly version
April 1, 2008
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Musician Gregg Allman is undergoing treatment for Hepatitis C. As one of the estimated five million Americans with this virus, Allman's fight against Hepatitis C reminds us that this disease affects people from all walks of life.
Gregg Allman has hepatitis C
Associated Press
www.news-journalonline.com
March 28, 2008
The Allman Brothers Band won't be peakin' at the Beacon for a while.
The rock band's annual spring run of concerts at New York City's Beacon Theatre has been postponed while co-founder Gregg Allman undergoes treatments for hepatitis C. The band also canceled their upcoming performances at the Wanee Festival, which they host every year in Live Oak.
"I'm getting better but I'm still tired," Allman said in a press release from Woody Graber, a public relations consultant for concert promoter Live Nation FL. "I need to be at 110% to do the shows the way we do them."
The Allman Brothers trace their roots to Daytona Beach, where Gregg and his late brother Duane first formed early incarnations of the band.
The Beacon dates, originally set for May 5-24, will be rescheduled. The Wanee Festival will go on as scheduled on April 11-12.
Posted by Editors at 9:20 AM --- Printer-friendly version