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EASL 2015: Shortening Triple Therapy to 6 Weeks Is Effective for Some Hepatitis C Patients


Shortening direct-acting antiviral therapy to 6 weeks for easier-to-treat patients without liver cirrhosis does not greatly reduce the efficacy of hepatitis C treatment for people with HCV genotype 1 infection, according to results of a study evaluating grazoprevir, elbasvir, and sofosbuvir (Sovaldi) in short treatment courses. Moreover, for people with HCV genotype 3 but no cirrhosis, an 8-week course of treatment was only marginally less effective than a 12-week course, even though genotype 3 infection is considered harder to treat.

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Fred Poordad of the Texas Liver Institute presented findings from the C-SWIFT trial at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna. Preliminary findings were presented previously at the 2014 AASLD Liver Meeting in November 2014.

C-SWIFT is a proof-of-concept study designed to test whether the use of an especially potent regimen consisting of Merck's grazoprevir (an HCV protease inhibitor) and elbasvir (an NS5A inhibitor) plus Gilead Science’s NS5B polymerase inhibitor sofosbuvir could shorten the duration of treatment for people with HCV genotypes 1 or 3.

The study recruited previously untreated people with liver enzyme (ALT and AST) levels below 350 IU/mL. A total of 143 patients were enrolled; 66% were male, 98% were white, 45% were Hispanic, and the mean age was approximately 52 years. Of the genotype 1 patients, 82% had harder-to-treat genotype 1a.

The study tested treatment durations of 4, 6, or 8 weeks for genotype 1 patients, and 8 or 12 weeks for genotype 3 patients. Genotype 3 is considered harder to treat than genotype 1. Participants in the study were randomized according to the following protocol:


Genotype 1

Genotype 3






Treatment duration (n)

4 weeks (31)

6 weeks (20)

8 weeks (15)

12 weeks (12)

6 weeks (30)

8 weeks (21)

12 weeks (14)

The primary efficacy analysis showed that a 4-week course of treatment for non-cirrhotic genotype 1 patients performed very poorly. Just 33% of these participants achieved a sustained virological response at 12 weeks post-treatment (SVR12), compared to 87% of those treated for 6 weeks in the non-cirrhotic group and 80% in the cirrhotic group. 94% of cirrhotic participants treated for 8 weeks achieved SVR12. No cases of viral breakthrough during treatment were observed. All but 4 treatment failures were cases of viral relapse; the remainder were due to treatment discontinuation.

In the genotype 3 group, an 8-week treatment course was marginally less effective than a 12-week course among non-cirrhotic participants (93% vs 100% SVR12), the difference being attributable to 1 case of viral relapse after completion of treatment. 91% of participants in the 12-week cirrhotic group achieved SVR12. A per-protocol sub-group analysis of genotype 3 participants showed a trend towards poorer virological response in people with baseline HCV RNA >2,000,000 IU/mL, but no other substantive differences in response were noted.

The only serious adverse events occurred in the cirrhotic genotype 1 group. One participant discontinued treatment due to the development of B cell lymphoma after 4 weeks, and 1 developed pyelonephritis. No cases of liver enzyme or total bilirubin elevation were observed.

Giving an overview of conference presentations on viral hepatitis treatment on the final day of the conference, Michael Manns of Hannover Medical School in Germany said that when shortening treatment for the easiest to treat patients, C-SWIFT showed that 6 weeks appears to be the barrier below which efficacy falls off.

Merck will continue research on shorter regimens composed of grazoprevir, the experimental nucleotide inhibitor MK-3682, and either elbasvir or the experimental NS5A inhibitor MK-8408, in people with genotypes 1, 2, 3, and 4.



F Poordad, E Lawitz, JA Gutierrez, et al. C-SWIFT: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis C virus genotype 1 infection, for durations of 4, 6 or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract O006.

Other Source

Merck. Merck Announces Presentation of Phase 2 Clinical Trial Results of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir at the International Liver Congress 2015. Press release. April 25, 2015.