Meeting News

New three-drug HCV regimen shows nearly 100% response in 6, 8 weeks

WASHINGTON — A novel triple therapy combination correlated with nearly perfect SVR12 rates in most patients treated for 6 or 8 weeks, according to findings presented at The Liver Meeting 2017.

“There is evidence that any shortening of treatment for hepatitis C may have potential to improve patient compliance, convenience, and tolerability,” Stefan Zeuzem, MD, of J. W. Goethe University, Frankfurt am Main in Germany, said. “The doses were chosen from a prior phase 2a study.”

Zeuzem and colleagues presented findings for a three-drug combination called JNJ-4178 that includes the NS5B inhibitor AL-335 (Achillion) at 800 mg, the NS5A inhibitor odalasvir (Achillion) at 25 mg, and Olysio (simeprevir, Janssen) at 75 mg once daily. Researchers followed eligible participants for 24 weeks after the end of treatment.

SVR12 served as the primary endpoint, and adverse events, laboratory abnormalities, electrocardiogram or echocardiogram, and pharmacokinetics served as secondary endpoints.

The study included 183 patients treated for 6 weeks and 182 treated for 8 weeks. HCV genotypes 1a and 1b comprised approximately 70% of the cohort, with genotypes 2 and 4 comprising about one-quarter and a small proportion having genotype 5 HCV. “We extended the genotypes to the phase 2b study,” Zeuzem said. “All genotypes but genotype 6 were enrolled. They were allowed to be enrolled.”

For the 8-week arm, 178 of 182 patients reached the primary endpoint, according to Zeuzem. In the 6-week arm, 181 of 183 patients reached SVR12. Zeuzem noted that these findings translated to an overall 98.9% SVR12 rate. “This of course also meets the non-inferiority to historical controls,” he said.

SVR12 rates were above 98% in every genotype except genotype 2, Zeuzem added. “Specifically, genotype 2c infection patients experienced relapses most frequently,” he said.

There were no grade 4 adverse events reported, no premature discontinuations of the study drug, and no laboratory abnormalities observed, according to Zeuzem. “There were typical adverse events, fatigue, headache, but nothing special in particular,” he said. “Extensive and thorough cardiac evaluation did not reveal any evidence for cardiotoxicity.”

There is some debate about the role of resistance variants in patients who failed to reach SVR12, particularly those with genotype 2 disease, according to Zeuzem. Most of the variants were found in patients with genotype 2c.

“Six and 8 weeks of treatment with [JNJ-4178] resulted in SVR rates of 99% and 98%, respectively,” Zeuzem concluded. – by Rob Volansky

For more information:

Zeuzem S, et al. Abstract 65. Presented at: The Liver Meeting; Oct. 20-24, 2017; Washington, D.C.

Disclosure: Zeuzem reports consulting for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck/MSD.

WASHINGTON — A novel triple therapy combination correlated with nearly perfect SVR12 rates in most patients treated for 6 or 8 weeks, according to findings presented at The Liver Meeting 2017.

“There is evidence that any shortening of treatment for hepatitis C may have potential to improve patient compliance, convenience, and tolerability,” Stefan Zeuzem, MD, of J. W. Goethe University, Frankfurt am Main in Germany, said. “The doses were chosen from a prior phase 2a study.”

Zeuzem and colleagues presented findings for a three-drug combination called JNJ-4178 that includes the NS5B inhibitor AL-335 (Achillion) at 800 mg, the NS5A inhibitor odalasvir (Achillion) at 25 mg, and Olysio (simeprevir, Janssen) at 75 mg once daily. Researchers followed eligible participants for 24 weeks after the end of treatment.

SVR12 served as the primary endpoint, and adverse events, laboratory abnormalities, electrocardiogram or echocardiogram, and pharmacokinetics served as secondary endpoints.

The study included 183 patients treated for 6 weeks and 182 treated for 8 weeks. HCV genotypes 1a and 1b comprised approximately 70% of the cohort, with genotypes 2 and 4 comprising about one-quarter and a small proportion having genotype 5 HCV. “We extended the genotypes to the phase 2b study,” Zeuzem said. “All genotypes but genotype 6 were enrolled. They were allowed to be enrolled.”

For the 8-week arm, 178 of 182 patients reached the primary endpoint, according to Zeuzem. In the 6-week arm, 181 of 183 patients reached SVR12. Zeuzem noted that these findings translated to an overall 98.9% SVR12 rate. “This of course also meets the non-inferiority to historical controls,” he said.

SVR12 rates were above 98% in every genotype except genotype 2, Zeuzem added. “Specifically, genotype 2c infection patients experienced relapses most frequently,” he said.

There were no grade 4 adverse events reported, no premature discontinuations of the study drug, and no laboratory abnormalities observed, according to Zeuzem. “There were typical adverse events, fatigue, headache, but nothing special in particular,” he said. “Extensive and thorough cardiac evaluation did not reveal any evidence for cardiotoxicity.”

There is some debate about the role of resistance variants in patients who failed to reach SVR12, particularly those with genotype 2 disease, according to Zeuzem. Most of the variants were found in patients with genotype 2c.

“Six and 8 weeks of treatment with [JNJ-4178] resulted in SVR rates of 99% and 98%, respectively,” Zeuzem concluded. – by Rob Volansky

For more information:

Zeuzem S, et al. Abstract 65. Presented at: The Liver Meeting; Oct. 20-24, 2017; Washington, D.C.

Disclosure: Zeuzem reports consulting for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck/MSD.

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