Hepatitis C treatment breakthrough
Kate Hagan
March 15, 2011
A NEW treatment for hepatitis C trialled in patients at The Alfred hospital has cut debilitating side effects and reduced treatment times, creating the potential for many more patients to be cured of the disease.
About 250,000 Australians have hepatitis C but only 5 per cent choose to have the current treatment due to multiple side-effects such as psychotic episodes, depression, insomnia and muscle aches and pains.
Current treatment involves weekly injections of interferon - a protein that fights the virus but causes the side effects - as well as twice-daily tablets for up to seven weeks.
But researchers have found that a combination drug without interferon is even more effective, curing some patients of the disease within two weeks in a recent trial.
The study, published in The Lancet and funded by the drug company Roche, involved 88 patients from six hospitals in Australia and New Zealand, including The Alfred.
The Alfred hospital's director of gastroenterology, Associate Professor Stuart Roberts, said the success of the combination drug - which inhibits enzymes that cause the virus to multiply - was an exciting breakthrough.
About 70 per cent of people with hepatitis C develop a chronic form of the virus. One-fifth of those patients develop cirrhosis - a scarring of the liver that can lead to cancer.
The blood-borne virus can be spread by sharing drug-injecting equipment such as needles, through needlestick injuries in healthcare settings, or from blood transfusions before 1990 that may not have been screened for the virus.
''The interferon-free treatment … will see a lot more people taking up treatment because of the lack of major side effects,'' Professor Roberts said.
''It may also open up opportunities to increase treatment outside specialist centres in the hospitals because there is less requirement for intensive care and monitoring of patients.
''Introducing this treatment as standard practice is a few years off, but this study provides a proof of concept that it can be effective,'' he said.
While the current treatment produces a 50 per cent cure rate, Professor Roberts said the new treatment may be up to 80 per cent effective and would be used far more widely.
''At the moment many patients elect to manage themselves conservatively and don't undergo treatment,'' he said.
''Treatment, when successful, can not only arrest the progression of the disease but often it will reduce in severity as the liver remodels itself.''
Hepatitis C infections have increased in Victoria, with 662 new cases reported by doctors during the second quarter of 2009 - 25 per cent more than in the same period in 2008.
The article did not have a link to the lancet abstract....I'm sure you have seen this, but here it is folks;
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The Lancet, Volume 376, Issue 9751, Pages 1467 - 1475, 30 October 2010
doi:10.1016/S0140-6736(10)61384-0Cite or Link Using DOI
Published Online: 15 October 2010
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial
Original TextDr Edward J Gane MD a , Stuart K Roberts MD b, Catherine AM Stedman MD c, Prof Peter W Angus MD d, Brett Ritchie MD e, Rob Elston PhD f, David Ipe MS f, Peter N Morcos PharmD f, Linda Baher BS f, Isabel Najera PhD f, Tom Chu MD f, Uri Lopatin MD f, M Michelle Berrey MD g, William Bradford MD h, Mark Laughlin MD f, Nancy S Shulman MD f, Patrick F Smith PharmD f
Summary
Background
Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs—RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor—in patients with chronic HCV infection.
Methods
Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13 days oral combination treatment with RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg every 8 h or 600 mg or 900 mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo.
Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13 days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov, NCT00801255.
Findings
88 patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose).
The median change in HCV RNA concentration from baseline to day 14 ranged from −3·7 to −5·2 log10 IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was −5·1 log10 IU/mL (IQR −5·6 to −4·7) in treatment-naive patients and −4·9 log10 IU/mL in previous standard of care null responders (−5·2 to −4·5) compared with an increase of 0·1 log10 IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.
Interpretation
This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV.
Funding
Roche Palo Alto.
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