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HIV and Hepatitis.com Coverage of
Digestive Disease Week 2006 (DDW 2006)
 May 20 - 25, 2006, Los Angeles, California

In Nonresponders to Peginterferon/Ribavirin, Valopicitabine Plus Peginterferon at Optimal Dosing Produces Significantly Greater HCV Suppression Compared to Retreatment with Peginterferon Alfa

HCV genotype 1 non-responders (NR) to pegIFN/RBV comprise over 50% of currently treated patients and have no proven treatment options. NM283 has shown anti-HCV activity alone and in combination with pegIFN in Phase I-IIa trials, without viral breakthrough for study periods up to 6 months.

This ongoing Phase IIb trial is comparing 5 treatments 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.

PegIFNa-2a (Pegasys) is dosed at 180 mg SQ/week with weight-based RBV (1000-1200 mg daily). Virologic response criteria are stipulated for week 4 (≥0.5 log reduction), week 12 (³1.0 log), and week 24 (≥2.0 log); patients who fail these criteria are designated treatment failures and discontinue.

Results  

Intent-to-Treat (ITT) results for the 162 patients who have reached week 24, including dropouts and failures by LOCF conventions:

 

Response at 24 Weeks

Treatment Group

N

Mean ¯ HCV RNA
(log10 IU/mL)

Median ¯ HCV (log10 IU/mL)

1  PegIFN + RBV control

31

2.31

  1.21

2  NM283 400 + pegIFN

40

 2.49

2.31

3  NM283 400-800 ramp + pegIFN

38

 3.01*

3.05

4  NM283 800 + pegIFN

32

 3.32*

3.29

5  NM283 monoRx

21

0.54

0.42

*p<0.03 pooled 800+peg-IFN vs peg-IFN

HCV RNA responses in the 2 higher-dose NM283+pegIFN comboRx 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 has been seen to date.

In conclusion, the authors write, “In non-responders to pegIFN/RBV, valopicitabine + 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.”

05/26/06

Reference

Paul Pockros, Christopher O’Brien, Eliot Godofsky, and others. Valopicitabine (NM283), Alone or with Peg-Interferon, Compared to Peg Interferon/Ribavirin (pegIFN/RBV) Retreatment in Hepatitis C Patients with Prior Non-Response to PegIFN/RBV: Week 24 Results. Abstract 4 (Presidential Plenary 1). DDW 2006. May 20-25, 2006. Los Angeles, CA.





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