Valopicitabine
plus Peginterferon Alfa-2a (Pegasys) Is More Effective in Nonresponders Compared
to Peginterferon alfa-2a/Ribavirin Combination Treatment
Nonresponders
(NR) to pegIFN/RBV with HCV
genotype 1 comprise the majority (>50%) of patients who are treated today
and they are currently without effective treatment options. Valopicitabine
(NM 283) is an experimental oral nucleoside analog from Idenix Pharmaceuticals.
The drug has shown anti-HCV activity alone and in combination with pegIFN in early
studies, without viral breakthrough for study periods up to 6 months. Interim
(24-week) results of an ongoing Phase IIb trial of valopicitabine
as monotherapy and in combination with peginterferon alfa-2a
were presented at the 41st EASL in Vienna, Austria,
April 26-30, 2006). The trial compares 5 treatment regimens in NR patients with
HCV-genotype 1, whose HCV RNA never became PCR-negative with >12 weeks
of pegIFN/RBV. All
patients had HCV RNA >5 log10 IU/mL by TaqMan PCR, ALT<5xULN, and
compensated disease. Patients
were randomized 1:2:2:2:2 among 5 treatments: NM283 monotherapy (800 mg/d), 3
combination (comboRx) arms with different NM283 dosing (400 mg/d; 800 mg/d; or
dose-ramping 400 to 800 mg/d) +pegIFN, or pegIFN/RBV retreatment as control. PegIFN
alfa-2a (Pegasys) is dosed at 180 microgram SQ/week with weight-based RBV
(1000-1200 mg daily). Virologic response criteria are stipulated for week 4 (>0.5
log reduction), week 12 (>1.0 log), and week 24 (>2.0 log);
patients who fail these criteria are designated treatment failures and discontinue.
24-week
Interim Results ITT
results for the 162 patients who have reached week 24, including dropouts and
failures: 
HCV RNA responses in the 2 higher-dose NM283+pegIFN combination treatment arms
arms are significantly greater vs pegIFN/RBV retreatment.
By comparison to other Phase IIb data, early HCV RNA reductions are substantially
greater in HCV-1 treatment-naïve patients with similar NM283/pegIFN regimens,
confirming the difficulty in suppressing HCV in NR patients.
No viral breakthrough seen to date.
GI side effects common with valopicitabine/pegIFN
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The
authors conclude, "In non-responders to pegIFN/RBV, valopicitabine plus pegIFN
treatment at optimal dosing produces significantly greater HCV suppression compared
to pegIFN/RBV retreatment, with antiviral efficacy proportional to valopicitabine
dose." "Continued
treatment will determine if these encouraging viral responses at 24 weeks will
result in viral clearance and SVR." 05/12/06 Reference
N
Afdhal N, C O'Brien C, E Godofsky, and others. Valopicitabine (NM283), alone or
with peg-interferon, compared to peg-interferon/ribaviri (pegIFN/RBV) re-treatment
in hepatitis C patients with prior non-response to pegIFN/RBV: week 24 results.
Abstract 483. Program and abstracts of the 41st Annual Meeting of the European
Association for the Study of the Liver. April 26-30, 2006. Vienna, Austria. Additional
Valopicitabine (NM 283) Articles
|
Valopicitabine (NM 283)
- Monotherapy
Randomized
Trial of Valopicitabine (NM 283), Alone or with Peginterferon, vs Retreatment
with Peginterferon Plus Ribavirin in Nonresponders to Peginterferon Alfa
- 11/14/05
No
Effect of Pegylated Interferon Alfa-2b (PegIntron) on the Pharmacokinetics of
Valopicitabine (NM 283) in Chronic HCV Patients
- 11/14/05
Update
on Experimental Therapies for Chronic Hepatitis C Infection - 10/26/05
Valopicitabine
(NM283) - DDW 2005 Showcases New Therapies for Chronic Hepatitis C - 5/20/05
Potency
of Novel New Nucleoside Valopicitabine Enhanced in Combination with Peginterferon
in HCVPatients with HCV Genotype 1 - 4/15/05
Pharmacokinetics
and Pharmacodynamics of Valopicitabine (NM283): Results from a Phase
I/II Dose Escalation Trial - 4/15/05
Efficacy,
Safety and Pharmacokinetics of NM 283, a New Polymerase Inhibitor for the
Treatment of Hepatitis C 11/01/04
Gilead and Genelabs Announce Collaboration for the Development and Commercialization
of Genelabs’ Hepatitis C Compounds - 10/04/04
NM283:
a Novel Nucleoside Analog That Specifically Inhibits the HCV RNA Polymerase
05/26/04
Dose Escalation Trial Assesses Tolerance, Pharmacokinetics, and Antiviral
Activity of NM 283, a Novel Antiviral Treatment for Hepatitis C - 05/24/04
Polymerase Inhibitors, NM283 and Isatoribine: HCV Experimental
Therapies in Early Stage Development -
01/14/04
Valopicitabine (NM 283) +/- peginterferon alfa-sa (Pegasys)
- Combination
Valopicitabine
Dosed in Combination with Pegylated Interferon Alfa-2a (Pegasys) Leads
to Rapid Virologic Response in 93 percent of Genotype 1 Hepatitis C Patients
-
1/10/06
Randomized
Trial of Valopicitabine (NM 283), Alone or with Peginterferon, vs Retreatment
with Peginterferon Plus Ribavirin in Nonresponders to Peginterferon Alfa - 11/14/05
No
Effect of Pegylated Interferon Alfa-2b (PegIntron) on the Pharmacokinetics
of Valopicitabine (NM 283) in Chronic HCV Patients - 11/14/05
Potency
of Novel New Nucleoside Valopicitabine Enhanced in Combination with Peginterferon
in HCV Genotype in Patients with HCV Genotype 1 - 4/15/05
Pharmacokinetics
and Pharmacodynamics of Valopicitabine (NM283): Results from a Phase
I/II Dose Escalation Trial - 4/15/05
Encouraging
Interim Results of Phase II Study of Valopicitabine (NM-283) in Combination
with Peginterferon Alfa in Patients with HCV Genotype 1 -
01/18/05
Safety,
Activity and Pharmacokinetics of the Combination of New Anti-HCV Compound
NM-283 Plus Pegylated Interferon 11/03/04
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