Shortening hepatitis C treatment to 6 weeks for
easier-to-treat patients without cirrhosis does not greatly reduce the efficacy
of hepatitis C treatment for people with genotype 1 infection, according to
results of a study combining grazoprevir, elbasvir and sofosbuvir in short
Moreover the study showed that for people with genotype 3
hepatitis C 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.
The findings of the C-SWIFT study were presented to the
International Liver Congress in Vienna, Austria, last month by Dr Fred Poordad of the
Texas Liver Institute, University of Texas. Preliminary findings were presented
previously at the American
Liver Meeting in November 2014.
type of tumour affecting the lymph nodes.
C-SWIFT is a proof-of-concept study designed to test whether
the use of an especially potent regimen of grazoprevir (an HCV protease
inhibitor) and elbasvir (an NS5A inhibitor) – two drugs in development by Merck – plus Gilead’s NS5B polymerase
inhibitor sofosbuvir (Sovaldi) could
shorten the duration of treatment for people with genotypes 1 or 3 hepatitis C.
The study tested treatment durations of 4, 6 or 8 weeks in people with genotype
1, and 8 or 12 weeks in people with genotype 3. Genotype 3 is considered
harder to treat than genotype 1. The study recruited previously untreated
people with hepatitis C genotypes 1 or 3 and liver enzyme (ALT and AST) levels
below 350 IU/ml.
Participants in the study were randomised according to the
4 weeks (31)
6 weeks (20)
8 weeks (15)
12 weeks (12)
6 weeks (30)
8 weeks (21)
12 weeks (14)
A total of 143 people were enrolled; 66% male, 98% white and 45%
Hispanic. Of the people with genotype 1, 82% had genotype 1a.
The primary efficacy analysis showed that a
4-week course of treatment in the group who did not have cirrhosis performed very poorly. Just 33%
of participants achieved a sustained virological response, compared to 87% of
those treated for 6 weeks in the group without cirrhosis and 80% in the
group with cirrhosis. Ninety-four per cent of participants with cirrhosis treated for 8 weeks achieved a sustained
virological response. No cases of viral breakthrough during treatment were
observed. All but four treatment failures were cases of virological relapse; the
remainder of treatment failures were due to treatment discontinuation.
In the genotype 3 group, an 8-week treatment
course was marginally less effective than a 12-week treatment course among participants without cirrhosis (93% vs 100% SVR12), the difference being
attributable to one case of virological relapse after completion of treatment.
Ninety-one per cent of participants in the 12-week group with cirrhosis achieved a sustained
virological response. A per-protocol sub-group analysis of people with genotype 3 showed a trend towards poorer virological response in people with
baseline HCV RNA > 2,000,000 IU/ml, but no other substantive differences in
The only serious adverse events occurred in
the group with cirrhosis and genotype 1. One participant discontinued treatment due to
the development of B-cell lymphoma after four weeks, and one developed
pyelonephritis. No cases of liver enzyme or total bilirubin elevation were
Giving an overview of conference
presentations on viral hepatitis treatment on the final day of the conference, Professor
Michael Manns of Hannover Medical School, 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 into shorter
regimens, composed of grazoprevir, the experimental nucleotide inhibitor
MK-3682 and either elbasvir or the experimental NS5A inhibitor MK-8408, in
genotypes 1, 2, 3 and 4.