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Shortened duration triple therapy fails in genotype 3 HCV

AMSTERDAM — Six weeks of triple combination therapy induced sustained virologic response in a cohort of patients with genotype 1 HCV but not genotype 3, according to data presented at the International Liver Congress.

“We observed 100% SVR24 for genotype 1, treatment-naive, non-cirrhotic patients who received a triple combination for either 8 or 6 weeks,” Ed Gane, MD, professor of medicine and chief hepatologist, transplant physician and deputy director of the New Zealand Liver Transplant Unit at the University of Auckland in New Zealand, said in his presentation. “However, when you remove simeprevir, the efficacy in genotype 1 is reduced. There was also reduced efficacy of a three-DAA regimen in genotype 3 for 8 weeks.”

Gane said that the rationale for the current study was to determine whether combining three different drugs with different mechanisms of action could allow the duration of therapy to be shortened. In the current study, AL-335 (Achillion) and odalasvir (Achillion) with or without Olysio (simeprevir, Janssen) were studied in a cohort of patients with genotype 1 and 3 disease in New Zealand.

The study included 20 patients with genotype 1 treated with an adjusted dose of the triple regimen for 8 weeks; 33 patients with genotype 1 treated with the double regimen for 8 weeks; 20 patients with genotype 1 treated with the triple regimen for 6 weeks; 20 patients with genotype 1 treated with the triple regimen for 8 weeks; and 19 patients with genotype 3 treated for 8 or, ultimately, 12 weeks. “This was an adaptive cohort study to optimize dose and duration,” Gane said.

Sustained viral response at a number of time points, mainly 12 weeks, served as the primary endpoint. The researchers also investigated safety parameters.

Gane presented the first group of results as a comparison of outcomes for the adjusted dose of the triple regimen versus double therapy for 8 weeks in genotype 1. Results indicated 100% SVR12 for the triple regimen and 84% for the double regimen. When treatment was continued for 12 weeks in the double regimen group, the rate increased to 88%. “Certainly, the optimal regimen for 8 weeks seems to be the three-DAA regimen,” Gane said.

For the next comparison, the researchers compared 6 and 8 weeks of therapy with the triple regimen in patients with genotype 1 disease. Both groups of 20 patients reached 100% SVR12.

For the final question, the researchers investigated 8 weeks of triple therapy in the genotype 3 cohort. “The first five patients in this group relapsed soon after completing therapy,” Gane said. “Based on these disappointing results, the remainder of the cohort had 12 weeks of therapy.”

Ultimately, after 12 weeks, 77% of genotype 3 patients responded to the triple regimen.

Safety data indicated that the regimen was generally well tolerated, with two serious adverse events. Baseline polymorphism data indicated no impact of RAS’s on outcomes, according to Gane. – by Rob Volansky

Reference: Gane E, et al. PS-153. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: Gane reports being a consultant for AbbVie, Achillion, Gilead Sciences, Janssen/Alios, and Merck.

AMSTERDAM — Six weeks of triple combination therapy induced sustained virologic response in a cohort of patients with genotype 1 HCV but not genotype 3, according to data presented at the International Liver Congress.

“We observed 100% SVR24 for genotype 1, treatment-naive, non-cirrhotic patients who received a triple combination for either 8 or 6 weeks,” Ed Gane, MD, professor of medicine and chief hepatologist, transplant physician and deputy director of the New Zealand Liver Transplant Unit at the University of Auckland in New Zealand, said in his presentation. “However, when you remove simeprevir, the efficacy in genotype 1 is reduced. There was also reduced efficacy of a three-DAA regimen in genotype 3 for 8 weeks.”

Gane said that the rationale for the current study was to determine whether combining three different drugs with different mechanisms of action could allow the duration of therapy to be shortened. In the current study, AL-335 (Achillion) and odalasvir (Achillion) with or without Olysio (simeprevir, Janssen) were studied in a cohort of patients with genotype 1 and 3 disease in New Zealand.

The study included 20 patients with genotype 1 treated with an adjusted dose of the triple regimen for 8 weeks; 33 patients with genotype 1 treated with the double regimen for 8 weeks; 20 patients with genotype 1 treated with the triple regimen for 6 weeks; 20 patients with genotype 1 treated with the triple regimen for 8 weeks; and 19 patients with genotype 3 treated for 8 or, ultimately, 12 weeks. “This was an adaptive cohort study to optimize dose and duration,” Gane said.

Sustained viral response at a number of time points, mainly 12 weeks, served as the primary endpoint. The researchers also investigated safety parameters.

Gane presented the first group of results as a comparison of outcomes for the adjusted dose of the triple regimen versus double therapy for 8 weeks in genotype 1. Results indicated 100% SVR12 for the triple regimen and 84% for the double regimen. When treatment was continued for 12 weeks in the double regimen group, the rate increased to 88%. “Certainly, the optimal regimen for 8 weeks seems to be the three-DAA regimen,” Gane said.

For the next comparison, the researchers compared 6 and 8 weeks of therapy with the triple regimen in patients with genotype 1 disease. Both groups of 20 patients reached 100% SVR12.

For the final question, the researchers investigated 8 weeks of triple therapy in the genotype 3 cohort. “The first five patients in this group relapsed soon after completing therapy,” Gane said. “Based on these disappointing results, the remainder of the cohort had 12 weeks of therapy.”

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Ultimately, after 12 weeks, 77% of genotype 3 patients responded to the triple regimen.

Safety data indicated that the regimen was generally well tolerated, with two serious adverse events. Baseline polymorphism data indicated no impact of RAS’s on outcomes, according to Gane. – by Rob Volansky

Reference: Gane E, et al. PS-153. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: Gane reports being a consultant for AbbVie, Achillion, Gilead Sciences, Janssen/Alios, and Merck.

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