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 any genotype (1,
2, 3, 4, 5 and 6) of chronic hepatitis C.
Epclusa is a
pangenotypic interferon-free hepatitis C treatment regimen, meaning it works
against all hepatitis C genotypes. 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.
How does Epclusa
Epclusa 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.
Blocking two steps in the lifecycle of the virus stops it from
reproducing and clears the virus from the body rapidly.
The aim of treatment is to achieve a sustained virologic response 12
weeks after completing treatment. If the hepatitis C virus remains undetectable
at this point, it means the virus has been cleared from the body and a person
is cured of hepatitis C.
Who can use Epclusa?
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 infections.
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 transplant.
How is Epclusa
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.
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 with Epclusa.
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.
Epclusa works 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
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 treatment.
sustained virological response, who have undetectable HCV viral load 12 and 24
weeks after finishing treatment (known as ‘SVR12’and ‘SVR24’), are considered
The phase 3
ASTRAL studies showed that the drugs in Epclusa, sofosbuvir plus
velpatasvir, are highly effective against all genotypes of HCV.
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
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.
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.
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.
What are the
side effects of Epclusa?
Epclusa is generally
well-tolerated. The most common side effects reported in clinical trials, affecting
more than one in a hundred people, were vomiting and rash. The drugs in Epclusa
have not been tested in pregnant or breastfeeding women. 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.
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.
Epclusa can 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.
How can I get
Epclusa is approved
in the European Union to treat people with hepatitis C genotypes 1 through 6. Ask
your GP or liver specialist if Epclusa is available in your country and
if it may be a good option for you.
Factsheet reviewed March 2022.