Multi-Genotype Hepatitis C Test Drug Successful in Phase 3 Trials

Results from three clinical trials of an investigational drug being developed by AbbVie to treat all major genotypes of the hepatitis C virus show high cure rates at or above 95% among patients tested.

Results from three clinical trials of an investigational drug being developed by AbbVie to treat all major genotypes of the hepatitis C virus show high cure rates at or above 95% among patients tested, according to a company release.

The phase 3 trials involved patients with chronic infection of hepatitis C who had never received treatment, or were not cured with previous interferon-based treatments, and did not have cirrhosis. Long-term infection of the virus can cause serious liver illness including cirrhosis, late stage scarring of liver tissue that can lead to dysfunction.

Each trial tested patients with specific HCV genotypes and success rates varied slightly, ranging from 95% to 99% depending on the genotype, according to data that AbbVie released at a meeting of the American Association for the Study of Liver Diseases in Boston.

“The results we announced today bring us closer to providing a potential pan-genotypic, once-daily treatment option with 8 weeks of therapy for people living without cirrhosis and who are new to treatment,” Michael Severino, MD, AbbVie’s executive vice president of research and development and chief scientific officer, stated in the release. “With our registrational program nearing completion, we’re on track to submit our next generation, pan-genotypic regimen to regulatory authorities by the end of this year in the US and early 2017 in the European Union and Japan.”

The results come from three open-label, multicenter studies that AbbVie conducted to evaluate the safety and efficacy of a regimen (dosed once daily as three oral tablets) for treatment of all six major genotypes (GT1-6) of the hepatitis C virus. The investigational regimen is a ribavirin-free coformulation of a glecaprevir, an NS3/4A protease inhibitor being developed with Enanta Pharmaceuticals and pibrentasvir, an NS5A inhibitor.

Patients were given treatment for eight weeks and the primary efficacy endpoint was sustained virologic response (SVR) -meaning no detectable virus- 12 weeks after treatment ended. Across the eight-week arms of all three studies, no patients stopped taking the drug because they experienced adverse reactions, according to the release.

The Endurance-1 trial tested 351 patients with genotype 1 HCV and showed a 99% success rate, while Endurance-3 tested 157 patients with genotype 3 HCV and had a 95% success rate. The third trial, called Surveyor 2 (part 4), tested a total of 203 patients from the remaining major genotypes 2, 4, 5 and 6 and resulted in a 97% success rate, according to AbbVie.

Overall in more than 700 patients without cirrhosis who had chronic infection of various genotypes of HCV and were new to treatment 693 patients out of 711 or 97.5% had SVR 12 weeks after they were treated with the investigational drug. The rate of virologic failure was 1% (nine patients), the release states.

The most common side effects (adverse events) of the investigational drug were headache and fatigue, occurring at a rate greater than 10% but no more than 20% across studies. There were no clinically relevant laboratory abnormalities observed, including no changes in the liver enzyme alanine aminotransferase, according to the release.

The initial data of the SVR rates are considered “particularly promising” given that most patients living with hepatitis C have earlier stages of liver disease and have never been treated for the virus, one of the investigators involved in the study, Stefan Zeuzem, MD, Chief of the Department of Medicine at the J.W. Goethe University Hospital in Frankfurt, Germany, stated in the release.

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