New Oral Direct-Acting Antiviral Drug Combination Offers New Hope for Treating Patients With Hepatitis C
NEW YORK -- October 14, 2010 -- For patients with the most common and difficult-to-treat form of hepatitis C virus (HCV), a new oral, direct-acting, experimental drug combination is safe and well tolerated, and shows promising antiviral activity, according to a study published early online and appearing in an upcoming edition of The Lancet.
Importantly, in some patients with no response to interferon-based standard therapy, the virus was undetectable after just 13 days of taking the combined treatment.
The authors suggest that 8 to 12 weeks of this regimen could be sufficient to cure many patients with hepatitis C, as long as resistance does not develop.
Treatment with interferon and ribavirin has significant side-effects, and moreover, only cures about half of patients. Thus, there is an urgent need for the development of a treatment regimen of direct-acting antiviral drugs with different mechanisms of stopping the virus and a higher barrier to resistance, which can improve cure rates and shorten treatment time.
The INFORM-1 trial was designed to assess the safety, tolerability, and antiviral activity of an oral combination treatment with 2 experimental drugs, RG7128 (a polymerase inhibitor that blocks elongation of the new HCV RNA chain) and danoprevir (a protease inhibitor that blocks an enzyme the virus needs to replicate itself) in patients with chronic HCV.
A total of 88 patients with HCV genotype 1 were recruited into 1 of 7 treatment groups and randomised to receive various doses and schedules of the combined treatment (n = 74) or placebo (n = 14) for up to 13 days. Some patients had never been treated before, while others had failed interferon-based standard therapy. Change in HCV RNA concentration was measured at the start of the study and at regular intervals during treatment up to day 14.
Patients who had never been treated before who received the highest doses of the 2 drugs (1000 mg RG7128 and 900 mg danoprevir BID) had a median HCV RNA reduction after 14 days of 5.1 log10 IU/ml, compared with a reduction of 4.9 log10 IU/ml in patients who had shown no response to previous standard treatment, and an increase of 0.079 log10 IU/ml in patients taking placebo.
The combined treatment of RG7128 and danoprevir was generally well tolerated with no treatment-related severe side-effects, and no safety-related treatment discontinuations.
In addition, there was no evidence of treatment resistance, unlike the rapid development of resistance shown by some classes of direct-acting antiviral drugs when given as monotherapy.
"The combination of RG7128 and danoprevir should be further developed and might be a viable interferon-free all-oral regimen for patients with chronic HCV infection," the authors concluded.
In an accompanying comment, David Thomas, MD, Johns Hopkins School of Medicine, Baltimore, Maryland, pointed out that even a 100% effective treatment will not cure many of those infected because, "only a small fraction of the estimated 170 million individuals with chronic hepatitis C infection know they are infected; far fewer ever start treatment. On the other hand, if interferon-sparing treatment is safer, more effective, and simple to administer, such an approach could markedly expand testing, treatment uptake, and treatment efficacy, similar to how the development of highly active antiretroviral therapy led to expanded testing and treatment of HIV."
SOURCE: The Lancet
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