492 A phase II, placebo-controlled study of merimepodib (XV-497), in combination with pegylated interferon-alfa, and ribavirin in patients with chronic hepatitis C non-responsive to previous therapy with interferon-alfa and ribavirin

Marcellin, Patrick; Horsmans, Yves; Nevens, Frederik; Grange, J D; Jp, Bronowicki; Vetter, D; Kauffman, R. G.; Knox, Steven J.; McNair, Lindsay; Moseley, Scott

doi:10.1016/s0168-8278(04)90492-8

Cited by 8 publications

(4 citation statements)

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“…In treatment-naïve CHC patients, a 4-week course of interferon/VX-497 combination treatment did not significantly affect viremia as compared to interferon alone . In contrast, in nonresponders to interferon/ribavirin, the addition of VX-497 to peginterferon/ribavirin significantly improved on-treatment response at week 24 (Marcellin et al, 2004).…”

Section: Vx-497 (Merimepodip)mentioning

confidence: 81%

Novel approaches for therapy of chronic hepatitis C

Stauber

Stadlbauer

2006

Journal of Clinical Virology

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Section: Vx-497 (Merimepodip)mentioning

confidence: 81%

Novel approaches for therapy of chronic hepatitis C

Stauber

Stadlbauer

2006

Journal of Clinical Virology

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“…VX‐497 (Merimepodip) is a potent, specific and orally taken inhibitor of IMPDH. Although it has been found that VX‐497 monotherapy may increase viral replication because of T‐cells inactivation 40 and IFNα plus VX‐497 combination did not have stronger anti‐viral activity than IFNα monotherapy in naïve CHC patients, 41 the addition of VX‐497 to PEG‐IFNα and RBV was reported to improve significantly the virological response at week 24 in nonresponders CHC patients 42 …”

mentioning

confidence: 99%

Review article: novel therapeutic options for chronic hepatitis C

Papatheodoridis

2008

Aliment Pharmacol Ther

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“…Larger, longer duration treatment trials incorporating PEG-IFN, and using MMPD either alone or in combination with RBV, are required to further explore the findings from this study. A small Phase II study, which evaluated the safety of the triple combination (PEG-IFN, RBV and MMPD), has been completed [25] and a study designed to evaluate the effect of this regimen on SVR rates is in progress.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Trial of Merimepodib (VX-497) and Interferon-α in Previously Untreated Patients with Chronic Hepatitis C

et al. 2005

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Inhibition of inosine monophosphate dehydrogenase (IMPDH) is one of several proposed mechanisms of action for ribavirin (RBV), a critical component of the current treatment for chronic hepatitis C (CHC). This study was a double-blind, placebo-controlled dose-escalation study of a novel, selective, orally active small molecule inhibitor of IMPDH, merimepodib (VX-497 or MMPD) in combination with standard interferon-alpha (IFN-α). Fifty-four treatment-naive patients with genotype-1 CHC were randomized to receive IFN-α 3 MIU subcutaneously three times a week, alone or in combination with 100 mg or 300 mg (every 8 h) of MMPD for 4 weeks. At the end of 4 weeks, all patients were offered 48 weeks of treatment with IFN-α/RBV. The objectives of the study were to evaluate the tolerability of the IFN-α/MMPD combination and to evaluate whether MMPD had an on-treatment effect on HCV-RNA, similar to RBV when added to IFN-α. The drug combination was generally well tolerated; one patient at the higher dose discontinued because of elevated alanine aminotransferase levels. No pharmacokinetic interactions were evident between the two drugs. Analysis of covariance that adjusted for a baseline imbalance in HCV-RNA in the intent-to-treat population did not show any significant differences between the treatment groups, or between MMPD plus IFN-α compared with IFN-α alone. However, the per-protocol primary efficacy analysis based on treatment-compliant patients demonstrated a greater reduction in mean HCV-RNA in the combination of 100 mg MMPD plus IFN-α compared with IFN-α alone (-1.78 log vs -0.86 log, P=0.037). In conclusion, the addition of a selective IMPDH inhibitor to IFN-α was well tolerated. In a low-dose range, the addition of MMPD may have the potential to add to the antiviral efficacy of IFN-α. Larger, longer duration trials incorporating pegylated IFN would be required to determine whether this combination, alone or with RBV, would increase either early or sustained virological response rates.

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492 A phase II, placebo-controlled study of merimepodib (XV-497), in combination with pegylated interferon-alfa, and ribavirin in patients with chronic hepatitis C non-responsive to previous therapy with interferon-alfa and ribavirin

Cited by 8 publications

References 0 publications

Novel approaches for therapy of chronic hepatitis C

Novel approaches for therapy of chronic hepatitis C

Review article: novel therapeutic options for chronic hepatitis C

A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Trial of Merimepodib (VX-497) and Interferon-α in Previously Untreated Patients with Chronic Hepatitis C

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