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C-SALT: Child-Pugh B patients respond to grazoprevir/elbasvir
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VIENNA — A novel combination regimen of grazoprevir and elbasvir was associated with favorable responses in a cohort of patients with advanced cirrhosis, according to findings presented at the 2015 International Liver Congress.
HCV Next Chief Medical Editor Ira M. Jacobson, MD, chair of the Department of Medicine at Mount Sinai Beth Israel Medical Center, co-director of the Liver Institute at Mount Sinai Health System and senior faculty at the Icahn School of Medicine at Mount Sinai, New York, presented findings for 30 Child-Pugh class B patients and 10 patients without cirrhosis. Patients in the cirrhotic group were treated with 50 mg grazoprevir and 50 mg elbasvir (MK-5172, MK-8742; Merck) once daily without ribavirin for 12 weeks. Patients without cirrhosis were evaluated in a pharmacokinetic analysis and treated with 100 mg grazoprevir and 50 mg elbasvir once daily for 12 weeks.
Ira M. Jacobson
“Patients with advanced cirrhosis have incompletely met needs,” Jacobson said. “No treatments exist for patients with Child-Pugh B.”
SVR12 served as the primary endpoint. The study was an intention-to-treat analysis.
All patients in the Child-Pugh B group had genotype 1 infection with a mean MELD score of 9.79 (SD, 2.46), mean albumin of 3.4 g/dL (range, 2.6-4.8) and mean platelet count of 83 × 103/mcL (range, 36-175).
Among cirrhotic patients, the response rates were 80% at week 4 of treatment, 100% at end of treatment, 93% at follow-up week 4 and 90% at follow-up week 8.
Regarding virologic failures, Jacobson said that two patients with cirrhosis relapsed. “There were no breakthroughs or rebounds,” he said. “There were no failures in the non-cirrhotic arm.”
MELD scores decreased in 11 patients, showed no change in 11 patients and increased in 6 patients, according to the findings.
Child-Pugh scores decreased in 18 patients, showed no change in seven patients and increased in four patients.
“We observed high rates of virologic response in Child-Pugh B,” Jacobson said.
There were no discontinuations due to adverse events. Jacobson reported no grade 3 or 4 AST or ALT elevations. “We did observe transient bilirubin elevations,” he said.
The serious adverse events that were observed were not related to study medications but to progression of liver disease, according to Jacobson.
Jacobson reported that in patients with or without cirrhosis, steady-state preliminary plasma C2h was 1.12 (0.62, 2.00), while C24h was 1.73 (0.87, 3.43) and AUCO-24 concentrations were 1.30 (0.76, 2.21) for grazoprevir. For elbasvir, C2h was 0.95 (0.70, 1.30), C24h was 1.07 (0.75, 1.53) and AUCO-24 was 0.93 (0.69, 1.25).
“This regimen was highly effective and well tolerated in a traditionally hard-to-treat group,” Jacobson said. “We saw no evidence of hepatotoxicity.” – by Rob Volansky
For More Information:
Jacobson IM, et al. Abstract O008. Presented at: International Liver Congress; April 22-26, 2015; Vienna.
Disclosure: Jacobson reports a relevant relationship with Merck.