Valopicitabine plus Peginterferon Alfa-2a (Pegasys) Is More Effective in Nonresponders
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
(
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
All patients had HCV RNA
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
(
fail these criteria are designated treatment failures and discontinue.
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.
http://www.hivandhepatitis.com/2006icr/easl/docs/051206_a.html
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
http://www.hivandhepatitis.com/2006icr/easl/docs/051206_a.html