HCV therapeutic research at Idenix is focused on the discovery and development of inhibitors of hepatitis C virus (HCV) replication that may offer significant therapeutic advantages over current anti-HCV agents. Using a process known as directed medicinal chemistry SAR (structure-activity relationship) analysis, we have discovered several nucleoside analogs that we believe will be active against various strains of HCV, including genotype 1, the most prevalent and most treatment-resistant HCV genotype found in the United States, Japan and Western Europe.
Idenix's hepatitis C program is seeking to address two large patient populations: those that have failed to respond to the current standard treatment, pegylated interferon plus ribavirin, and those that are treatment-naïve.
Idenix's lead drug candidate for the treatment of hepatitis C, valopicitabine (NM283), is currently in phase II clinical trials. Valopicitabine (NM283), which is administered orally once a day, is intended to block HCV replication by specifically inhibiting the HCV RNA polymerase.
MODE OF ACTION
Valopicitabine is an orally bioavailable pro-drug of a novel ribonucleoside analog, and is an inhibitor of HCV and related viruses. Valopicitabine targets the virus-encoded RNA polymerase that is responsible for synthesizing viral RNA during replication. Valopicitabine appears to act in two ways: it inhibits the viral polymerase directly and it is incorporated into growing strands of viral RNA, which terminates RNA chain extension. In contrast, human RNA dose not appear to be affected by valopicitabine, thus normal cellular functions seem to be protected from potential toxicity. Valopicitabine is the first antiviral agent of this class to enter clinical trials for the treatment of hepatitis C.
ONGOING PHASE II CLINICAL TRIAL DESIGNS
TREATMENT-REFRACTORY PATIENTS
(patients who have not responded to the current standard treatment)
Phase IIb
A 48-week trial designed to compare the combination of valopicitabine and PegasysR to the standard of care, pegylated interferon plus ribavirin therapy.
Enrollment of 190 treatment-refractory, HCV genotype 1 patients is complete
TREATMENT-NAÏVE PATIENTS
Phase IIa
30 treatment-naïve patients are enrolled in an ongoing trial to evaluate the safety and antiviral activity of valopicitabine combined with pegylated interferon.
Phase IIb
48-week trial to assess the safety and the dose related contribution of valopicitabine to the antiviral activity demonstrated by the combination of valopicitabine and pegylated interferon.
Enrollment concluded with 174 treatment-naïve patients chronically infected with HCV genotype 1.
Clinical Trial Results
TREATMENT-REFRACTORY
Valopicitabine combined with pegylated interferon
After 12 weeks of treatment, there was a statistically significant improvement in viral suppression in patients receiving valopicitabine combined with PegasysR. In addition, 12-week data shows significantly higher rates of early virologic respons, (EVR), in patients who received 800 mg of valopicitabine and PegasysR compared to patients who received treatment with the combination of ribavirin plus PegasysR. EVR is conventionally defined as a reduction of at least 2 log10 , or 99% or more, of HCV levels in a patient's blood serum by week 12 of treatment.
TREATMENT-NAIVE
Valopicitabine combined with pegylated interferon
Interim data from the phase IIa trial demonstrated that for the 10 patients who have reached 24 weeks of treatment with the combination of valopicitabine and pegylated interferon, the average viral load reduction was 4.2 log10, or greater than 99.99%, and eight of the 10 patients who reached 24 weeks of treatment on the combination regimen have achieved HCV levels in blood serum that are below detectable limits (PCR negative). The available 24-week data from this phase IIa clinical trial further indicates no evidence of viral breakthrough, or resistance, in any patients treated with either valopicitabine monotherapy or the combination of valopicitabine and pegylated interferon.
SAFETY AND TOLERABILITY
Valopicitabine is an investigational compound for the treatment of hepatitis C that is currently being evaluated in ongoing clinical trials. The most commonly occurring adverse events are gastrointestinal side effects. For most of the patients experiencing gastrointestinal side effects, the side effects (nausea, vomiting, and occasionally diarrhea) are generally mild to moderate, transient, and resolve while remaining on treatment. However, at the 800 mg/day dosing level, while most patients still report only mild side effects, a higher proportion report moderate or severe intensity to the gastrointestinal side effects compared to observations at the 200 to 400 mg/day dosing level, and may result in treatment discontinuation.
Валопицетабин - вторая фаза испытаний
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Майк Безухов
круто наверное, если не считать побочки в виде различных растройств ЖКТ. посмотрим, что дальше будет. Лет через пять где-то появится возможно в продаже, если всё пройдёт у них гладко. Новому поколению гепСных пригодится. предсавляю сколько курс терапии стоить будет: пег+вал-н. Миллион?:)
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дима
если считать побочки нынешних схем - то не хуже нынешнихю Обнадеживает, что неответчиков пробирает тоже от энтой ядреной микстуры.