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San Francisco – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found the combination of glecaprevir and pibrentasvir is highly effective and well tolerated in patients with chronic hepatitis C virus (commonly called HCV) genotype-1 infections who have prior treatment experience with sofosbuvir/NS5A inhibitor.
Although most patients with HCV genotype 1 infection can be cured of the infection with first-line direct-acting antiviral therapies, those who do not respond have few retreatment options, presenting a challenge to clinicians.
To address this, researchers from multiple centers in the United States took part in a randomized, controlled trial of a fixed-dose combination of once-daily 300 milligrams of glecaprevir (an NS3/4A protease inhibitor) and 120 milligrams of pibrentasvir (an NS5A inhibitor, also known as G/P).
“The G/P regimen given for 16 weeks was approved by the U.S. Food and Drug Administration for retreatment of HCV GT1-infected patients who failed a prior NS5Ai-containing regimen without prior exposure to a protease inhibitor, explains Mark Sulkowski, MD who is a professor of medicine at Johns Hopkins and the principle investigator of the study at the Hopkins site. “However, due the relatively small number of patients included in the registration trial, the AASLD/IDSA guidelines panel recommended this regimen as an alternative treatment option leading to uncertainty regarding the use this regimen in clinical practice for the re-treatment of persons with HCV genotype 1 infection who failed prior treatment with an NS5Ai-containing regimen,” he explains of what prompted the study.
One hundred seventeen patients participated in the study, which evaluated the G/P regimen for 16 weeks in compensated cirrhotic and non-cirrhotic patients with HCV genotype 1 infection who had previously failed on the combination of an NS5Ai with sofosbuvir. The patients were predominately male (82 percent) who ranged in age from 60-64 years, and the study included patients with HIV infection as well as patients who had undergone prior liver transplantation.
Patients who did not have cirrhosis were randomly assigned to receive G/P for either 12 or 16 weeks at a 2:1 ratio, and patients with cirrhosis were randomly assigned to receive G/P with ribavirin for 12 weeks or G/P alone for 16 weeks at a 1:1 ratio.
Patients were grouped by HCV genotype 1 subtype (1a and 1b), and the researchers monitored them to see if/when they achieved sustained virologic response (as marked by having no detectible HCV virus in their blood for 12 or more weeks after the last dose of treatment).
As of October 2018, sustained virologic outcomes data was available for 172 of the 177 study participants. Of those 172, 157 achieved sustained virologic response.
Among 126 patients without cirrhosis (data on one patient is still pending), 91 percent have reached sustained virologic response. Within this group, 78 patients received G/P for 12 weeks (a 90 percent sustained virologic response rate), and 48 patients received G/P for 16 weeks (a 94 percent sustained virologic response rate).
Among 46 patients with cirrhosis (data on four patients is still pending), 91 percent have reached sustained virologic response. Ninety-six percent of patients in this group who were randomized to 16 weeks of G/P achieved sustained virologic response.
Overall, the researchers found G/P was well-tolerated among study participants with fatigue, headache and nausea reported in 17 percent, 19 percent and 9 percent of participants, respectively. The addition of ribavirin was associated with more side effects. Eleven serious adverse events have been observed among nine participants in the study, including one death due to hepatocellular carcinoma; none of these events were classified as treatment-related. Complete safety, efficacy and resistance associated substitution data will be presented at The Liver Meeting®.
Editor’s note: This press release contains updated data that is not reflected in the published abstract but will be presented at The Liver Meeting®.
Dr. Mark Sulkowski will present these findings at AASLD’s press conference in Room 312-314 at the George R. Moscone Convention Center in San Francisco on Saturday, November 10 from 4:00 PM – 5:30 PM. The study entitled “High Efficacy of Glecaprevir/Pibrentasvir in Patients with Chronic HCV GT1 Infection Who Failed Prior Treatment with NS5A-Inhibitor Plus Sofosbuvir Regimens” will be presented on Sunday, November 12 at 10:30 AM in Room 154/156. The corresponding abstract (number 0226) can be found in the journal, HEPATOLOTY.