Valeant Pharmaceuticals posted results at the treatment week 12 analysis point for the phase IIb clinical trial for its antiviral compound, taribavirin, a prodrug of ribavirin in development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon.
The phase IIb trial is a US multi-centre, randomised, parallel, open-label study in 278 treatment-naïve, genotype 1 patients evaluating taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b. The control group is being administered weight-based dose ribavirin (800/1000/1200/1400mg daily) and pegylated interferon alfa-2b. Overall treatment duration is 48 weeks with a post-treatment follow-up period of 24 weeks. The primary endpoints for this study are viral load reduction at treatment week 12 and anaemia rates throughout the study.
The 12-week early viral response (EVR) data from the phase IIb study showed comparable reductions in viral load for weight-based doses of taribavirin and ribavirin. The anaemia rate was statistically significantly lower for patients receiving taribavirin in the 20mg/kg and 25mg/kg arms versus the ribavirin control arm.
The most common adverse events were fatigue, nausea, flu-like symptoms, headache and diarrhoea. The incidence rates among treatment arms were generally comparable except with respect to diarrhoea, where diarrhoea was approximately twice as common in taribavirin patients as ribavirin patients. However, the diarrhoea was generally mild and not treatment limiting for taribavirin or ribavirin patients.
In 2006 Valeant released data from its phase III VISER1 and VISER2 trials of taribavirin, administered in a fixed dose of 600 mg BID (approximately equivalent to 13-18 mg/kg), in which taribavirin did not meet its primary efficacy endpoint of comparable efficacy to weight-based dose ribavirin. In 2007, the company began this phase IIb study to evaluate higher doses of taribavirin than used in the VISER trials, while also employing a weight-based dosing regimen, consistent with the dosing regimen for ribavirin.
"Ribavirin continues to be a necessary part of hepatitis C treatment, and clinicians would welcome a ribavirin prodrug with a profile of similar efficacy with decreased anaemia," said Fred Poordad, M.D., Chief of Hepatology at the Centre for Liver Disease and Transplant, Cedars-Sinai Medical Centre, Los Angeles, California. "A drug with fewer required dose reductions for anaemia or a reduced need for adjunctive growth factor therapy may subsequently improve treatment adherence and overall response rate."
"We are encouraged that these data suggest that weight-based dosing with taribavirin at higher doses may have a role in the treatment of patients infected with hepatitis C while continuing to produce lower anaemia than ribavirin," said J. Michael Pearson, chairman and chief executive officer, Valeant. "However, we caution that these results only represent data from the first 12 weeks of a 72-week phase II trial that was designed to identify appropriate doses for further development. We will use these data to explore the best options for taribavirin's continued role in our portfolio, including consideration of partnering options."
In the study, the following percentages of patients completed 12 weeks of treatment in the taribavirin and ribavirin arms: 20mg/kg: 87.0 per cent; 25mg/kg: 80.0 per cent; 30mg/kg: 82.6 per cent; ribavirin 74.3 per cent. The following percentages of patients had adverse events leading to dose modification or interruption of taribavirin or ribavirin: 20mg/kg: 11.9 per cent; 25mg/kg: 15.7 per cent; 30mg/kg: 25.0 per cent; ribavirin 28.6 per cent.
In the Intent to Treat Analysis, the Rapid Virological Responses (RVR - virus undetectable at treatment week 4) in this study were 20mg/kg: 16.4 per cent; 25mg/kg: 14.3 per cent; 30mg/kg: 16.2 per cent; ribavirin: 11.4 per cent.
Taribavirin is an investigational compound that has not been found by the Food and Drug Administration (FDA) or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until FDA has approved a New Drug Application. Similar restrictions apply in other countries.