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Chronic hepatitis C virus genotype 1: Grazoprevir / Elbasvir in infected treatment-naïve and difficult-to-cure patients


The results from a multi-arm phase 2 clinical trial evaluating Grazoprevir / Elbasvir ( MK-5172 / MK-8742, the investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively ) with or without Ribavirin in treatment-naïve and previously-treated ( with Peg-Interferon / Ribavirin ) patients with chronic hepatitis C virus ( HCV ) genotype 1 ( GT1 ) infection, the C-WORTHy study ( Parts A and B ) were presented at the 65th American Association for the Study of Liver Diseases ( AASLD ) Annual Meeting ( also known as The Liver Meeting ) and published in The Lancet.

Treatment-naïve cirrhotic patients and Peg-Interferon / Ribavirin null-responders

In HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with Grazoprevir / Elbasvir, with or without Ribavirin, for 12 weeks or 18 weeks, the rates of sustained viral response, 12 weeks after the completion of therapy ( SVR12 ) were greater than, or equal to, 90% regardless of treatment duration or co-administration of Ribavirin.

The rate of virologic failure was 5% ( 6/123 ) in treatment-naïve cirrhotic patients and 3% ( 4/130 ) in the null-responder population.

Treatment was generally well-tolerated. The most common adverse events associated with the administration of Grazoprevir / Elbasvir in combination with or without Ribavirin were: fatigue ( 26% ), headache ( 23% ) and asthenia ( 14% ).
There were no early discontinuations due to adverse events with Grazoprevir / Elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

HCV mono-infected and HIV/HCV co-infected patients

Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with Grazoprevir / Elbasvir with or without Ribavirin, demonstrated high rates of SVR12.

Among this patient population treated for 12 weeks, the overall rate of virologic failure was 4% ( 7/188 ), including three breakthrough failures and four relapses, in both mono- and co-infected patients.
In patients treated for 8 weeks, the rate of virologic failure was 17% ( 5/30 ), with five relapses.

The most common adverse events with or without Ribavirin were fatigue ( 23% ), headache ( 20% ), nausea ( 15% ) and diarrhea ( 10% ).
There were no early discontinuations due to adverse events with Grazoprevir / Elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

C-WORTHy is a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of Grazoprevir / Elbasvir with or without Ribavirin in patients with chronic HCV infection.
In C-WORTHy Parts A and B, a total of 471 patients with chronic HCV GT1 infection with HCV RNA levels of greater than or equal to 10,000 IU/mL were enrolled and randomized across 16 arms.
The patients include hard-to-cure sub-populations, including treatment-naïve patients with liver cirrhosis ( 12- and 18-week arms, with and without Ribavirin ) and prior-null responder patients with and without cirrhosis ( 12- and 18-week arms, with and without Ribavirin ).

The results of the C-WORTHy study supported the advancement of Grazoprevir / Elbasvir into the phase 3 clinical development program called C-EDGE.
The Phase 3 C-EDGE program is evaluating Grazoprevir / Elbasvir with and without Ribavirin in various genotypes and across a broad range of patient populations with chronic HCV infection, including treatment-naive patients and patients who previously failed Peg-Interferon / Ribavirin therapy, patients with and without cirrhosis, patients with chronic kidney disease ( including those on hemodialysis ), patients with HIV/HCV co-infection, patients on opiate substitution therapy and patients with inherited blood disorders.

Source: Merck, 2014

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