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Viramidine Phase III Study-did not meet efficacy endpoint
Valeant looking at weight-based dosing of Viramidine based on post-hoc analysis
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Reported by Jules Levin
EASL, April 26-30, 2006, Vienna, Austria
"The Safety and Efficacy of Viramidine Plus PegIFN alfa-2b Versus Ribavirin Plus PegIFN alfa-2b in Therapy-Naive Patients Infected with HCV: Phase 3 Results (VISER1)"
Authors: Y. Benhamou, P. Pockros, M. Rodriquez-Torres, S. Gordon, M. Shiffman, Y. Lurie, N. Afdahl, K. Lamon, Y. Kim, B. Murphy
Background
- Peginterferon alfa-2b monotherapy results in sustained virologic response (SVR) of approximately 24%
- The addition of ribavirin to PegIFN nearly doubles the rate of SVR compared to monotherapy
- Anemia associated with PegIFN/ribavirin use occurs in approximately 25% of patients
- Viramidine is a liver targeting pro-drug of ribavirin resulting in less anemia
AUTHOR SUMMARY
- Superiority safety endpoint met
- Overall non-inferiority criterion not met on ITT analysis
- Lower rates of anemia compared to ribavirin were observed at higher Viramidine mg/kg exposure (weight-based dosing analysis performed post-hoc, after study completion)
- Increasing mg/kg exposure of Viramidine improves SVR (also based on post-hoc analysis of weight-based dosing, SEE GRAPHS BELOW)
SVR (ITT) rates were 38% for Viramidine vs 52% for ribavirin overall. In genotypes 1, 4, 5, & 6 SVR rate was 29% for Viramidine vs 42% for ribavirin. For genotypes 2/3, SVR rate was 62% for Viramidine & 78% for ribavirin. So, the primary study endpoint of efficacy was not met. Regarding anemia, 5% of patients receiving Viramidine vs 24% receiving ribavirin experienced anemia, so this endpoint was achieved. In a post-hoc analysis, after the study was completed, the company went back and performed an analysis to see if they had weigh-based dosed Viramidine would it have performed well, and it appeared to perform well. Efficacy improved while anemia increased a little. You can see the data in the graphs below. So, I think now Valeant is waiting to hear from the FDA how they can proceed; will they have to perform a prospective study of weght-based dosing Viramidine?
Viramidine Phase 3 (VISER1) Study:
Design
Randomized, Double-blind Multicenter, Parallel-group Study
in Treatment-naive Subjects (N = 970)
Stratified by Genotype, HCV RNA and Weight
HCV, NGI SuperQuant; sensitivity to 39 IU/mL
*Genotype 2, 3 = 24 weeks/1, 4, 5, 6 = 48 weeks
PegIFN alfa-2b 1.5 _g/kg/week
Co-Primary Endpoints
Primary Efficacy
Sustained Virologic Response at FW 24
- HCV RNA 39 IU/mL
Non-inferiority test vs. ribavirin
Primary Safety
Hemoglobin <10 g/dL or >/= 2.5 g/dL drop from baseline
Superiority test vs. ribavirin
Key Eligibility Criteria
- Treatment naive
- Compensated liver disease
- Liver Biopsy within 3 years consistent with HCV infection
- Hemoglobin
- Women: >/= 12.0 g/dL
- Men: >/= 13.0 g/dL
- BMI 18 to 35 kg/m2
DEMOGRAPHICS
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