Epclusa is a
new medication used to treat hepatitis C. It is a combination pill containing
sofosbuvir (sold separately as Sovaldi)
plus velpatasvir. It was approved in Europe in July 2016 for treatment of
adults with all genotypes (1, 2, 3, 4, 5 and 6) of chronic hepatitis C.
Epclusa is the
first pangenotypic interferon-free hepatitis C treatment regimen, meaning it
works against all hepatitis C genotypes. It is more effective than the older Harvoni combination (sofosbuvir + ledipasvir)
for people with genotype 3. Some people with harder-to-treat disease may do
better if they take Epclusa with ribavirin.
Successful treatment reduces the risk of long-term complications of hepatitis C
such as liver cancer or needing a liver transplant.
contains two direct-acting antiviral drugs that target different steps of the
hepatitis C virus (HCV) lifecycle. Sofosbuvir is a nucleotide analogue HCV polymerase
inhibitor, meaning it blocks the polymerase enzyme which the virus must use to
reproduce. Velpatasvir is an HCV NS5A replication complex inhibitor that
interferes with another protein HCV uses to reproduce.
Epclusa is approved
for use by adults with chronic hepatitis C, meaning infection lasting more than
six months. It is approved for people with HCV genotypes 1, 2, 3, 4, 5 and 6.
Genotype 1 is the most common type in Europe. Genotype 3 is considered hardest
to treat with direct-acting antivirals.
Epclusa can be
used by people being treated for hepatitis C for the first time (known as ‘treatment
naive’) and for retreatment of people who were not cured with previous therapy
(known as ‘treatment experienced’).
Epclusa has also
been tested in people with HIV and HCV co-infection. Response rates and side-effects
are similar to those seen in HIV-negative people, and Epclusa can be used with many HIV medications. People with HIV and
HCV co-infection who want to take Epclusa
should do so under the care of a doctor who has experience treating both
Epclusa can be
used by people with all stages of liver disease, including compensated cirrhosis,
decompensated cirrhosis (laboratory abnormalities or symptoms
of poor liver function) and people who are awaiting or have received a liver
How is Epclusa taken?
Epclusa is taken
as a single pill once daily with or without food. The length of treatment is 12
weeks for people with all HCV genotypes, with or without cirrhosis.
People with decompensated cirrhosis should add
ribavirin. Ribavirin may also improve effectiveness for people with genotype 3
and compensated cirrhosis. People who previously did not respond to earlier
treatment with a different NS5A inhibitor may benefit from longer treatment
Recommended uses for people with HIV and HCV co-infection
are the same as for HIV-negative people, but they should be cautious about
using antiretroviral medications that can interact with the drugs in Epclusa.
effective is Epclusa?
better for some people than for others. Several factors predict how well
someone will respond, including HCV genotype, extent of liver damage and
previous treatment history.
People with advanced liver disease do not respond as
well as those with mild or moderate liver fibrosis. This may be overcome by
adding ribavirin, which helps prevent relapse. People who are new to treatment
have a better chance of being cured than those who did not respond to prior
People with sustained virological response, who have
undetectable HCV viral load 12 and 24 weeks after finishing treatment (known as
‘SVR12’and ‘SVR24’), are considered cured.
The phase 3 ASTRAL studies showed that the drugs in Epclusa, sofosbuvir plus velpatasvir, are
highly effective against all genotypes of HCV.
ASTRAL-1 tested Epclusa
without ribavirin in more than 700 previously untreated and
treatment-experienced people with HCV genotypes 1, 2, 4, 5 and 6, while
ASTRAL-2 focused on people with genotype 2. In both studies 99% of participants
ASTRAL-3 enrolled more than 500 people with
hard-to-treat genotype 3. The cure rate was 95% for people taking Epclusa for 12 weeks compared to 80% for
those taking sofosbuvir plus ribavirin for 24 weeks.
The ASTRAL-4 study showed that Epclusa works for people with decompensated cirrhosis. Cure rates were 83% for those treated
with Epclusa alone for 12 weeks and
94% for those who added ribavirin.
ASTRAL-5 showed that people with HIV and HCV
co-infection had response rates similar to those of HIV-negative people,
ranging from 92% for genotype 3 to 100% for genotypes 2 and 4.
effectiveness in ‘real world’ use may be somewhat lower than cure rates seen in
clinical trials, in part because patients may be sicker or have other
conditions that make treatment more complicated.
the side-effects of Epclusa?
generally well-tolerated. The most common side-effects reported in clinical
trials were headache, fatigue
and nausea. The drugs in Epclusa have
not been tested in pregnant or breastfeeding women, or in children and
adolescents with hepatitis C. Epclusa
has not yet been tested in people with advanced decompensated cirrhosis (Child-Pugh
C) or people with severe kidney dysfunction or haemodialysis. Ribavirin
can cause side-effects including anaemia. It can also cause birth defects, so
it should not be used by pregnant women or their male partners.
Does Epclusa interact with other drugs?
The drugs in Epclusa
can interact with other drugs that are processed by the same enzymes in the
liver or intestines. This can lead to low drug levels that are less effective
or high levels that can cause worse side-effects. People taking other medicines
or natural remedies should consult with their doctor before starting treatment
The drugs in Epclusa
can interact with some TB medications, psychiatric drugs, cholesterol-lowering
drugs, proton pump inhibitors, the heart medication amiodarone and herbal
products containing St John's wort.
raise levels of the HIV drug tenofovir (Viread,
also in several antiretroviral co-formulations), so people taking these drugs
together should have their kidney function checked regularly. Information about
other specific drug interactions is available online at www.hep-druginteractions.org.
I get Epclusa?
Epclusa is approved
in the European Union to treat people with hepatitis C genotypes 1 through 6. When
to start treatment will depend on a number of factors, including severity of
liver damage (as determined by FibroScan
or a liver biopsy). Ask your GP or liver specialist if Epclusa is available in your country and if itmay be a good option for you.