The first presentation looked at a pair of studies
evaluating sofosbuvir/velpatasvir plus GS-9857 in treatment-experienced
patients with HCV genotypes 1-6, a majority of whom were not cured with
previous regimens containing older NS5A inhibitors or multiple DAA drug classes.
These multicentre phase 2 studies included 128
participants in the US and New Zealand. Study GS-US-367-1168 enrolled only
people with HCV genotype 1, while GS-US-367-1169 enrolled people with all
A majority of participants (75%) were men, most were
white and the mean age was 58 years. About half had HCV genotype 1, 16% had
genotype 2, 27% had genotype 3 and 7% had genotype 4 or 6. A majority had
unfavourable IL28B gene patterns and nearly half had liver cirrhosis.
About 80% of participants (all genotype 1 patients and
a majority of genotype 2-6 patients) had previously used DAAs and half had
tried drugs from two or more drug classes; the remaining genotype 2-6 patients
had tried interferon/ribavirin without DAAs. Just over a quarter (27%) had
previously used NS5A inhibitors. At baseline a majority (60%) had some resistance-associated
variants (RAVs) – HCV mutations that confer drug resistance.
All participants in these open-label studies received
sofosbuvir/velpatasvir as a fixed-dose coformulation (400/100mg) plus GS-9857,
both taken orally once daily for 12 weeks.
A study of this combination presented last November at the AASLD
Liver Meeting showed that a 6-week regimen was not long enough, and while 8 weeks worked well
overall, the response rate with this duration was lower for people who had
previously used DAAs, thus 12 weeks was chosen for the present trials.
The primary endpoint was sustained virological
response, or continued undetectable HCV RNA at 12 weeks after completion of
The overall SVR12 rate was 99%. Cure rates were 100%
for people with genotypes 1, 2 and 4/6. The rate was 97% for genotype 3, with
one patient relapsing at 8 weeks post-treatment.
The sole relapser was a 58-year old white woman with
cirrhosis and a pre-treatment HCV viral load of 7 log10 IU/ml. She
had a NS5A RAV but no NS3 or NS5B RAVs at baseline. After treatment failure she
had a new NS3 RAV.
The likelihood of a cure did not differ significantly based
on presence of liver cirrhosis, prior use of NS5A inhibitors or the number of
previous DAA classes used. SVR12 rates were 100% for people without and 99% for
those with pre-treatment RAVs.
Treatment with sofosbuvir/velpatasvir plus
GS-9857 was generally safe and well-tolerated. The most common adverse
events were headache, fatigue, diarrhoea and nausea, mostly mild or moderate.
There were no clinically significant laboratory abnormalities. One person discontinued
treatment early due to gastritis but nevertheless achieved SVR12.