Sofosbuvir (brand name
Sovaldi) is a new medication used to
treat hepatitis C. It was approved in Europe
in January 2014 for treatment of adults with all genotypes of chronic hepatitis
For some people,
sofosbuvir will be the first interferon-free hepatitis C treatment option. For
others, sofosbuvir can greatly shorten treatment when added to pegylated
interferon and ribavirin. Successful treatment reduces the risk of long-term
complications of hepatitis C such as liver cancer or needing a liver
How does sofosbuvir work?
Sofosbuvir is one of
the new direct-acting antiviral drugs that target different steps of the
hepatitis C virus (HCV) lifecycle. It is a nucleotide analogue HCV polymerase
inhibitor, meaning it blocks the polymerase enzyme which the virus must use to
reproduce. Sofosbuvir should be combined with other medications, which may
include pegylated interferon (which stimulates the body's own immune response),
ribavirin or other direct-acting antivirals that work differently.
Who can use sofosbuvir?
indicated for use by adults with chronic hepatitis C, meaning infection lasting
more than six months. It is approved for people with HCV genotype 1, 2, 3, 4, 5
or 6. Genotype 1 is the most common type in Europe
and considered the hardest to treat.
Sofosbuvir 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 interferon-based therapy (known as 'treatment-experienced').
Sofosbuvir has also
been tested in people with HIV and HCV co-infection. Response rates and side-effects
are similar to those of HIV-negative people, and sofosbuvir does not interact
with HIV drugs. People with co-infection who want to take sofosbuvir should do so
under the care of a doctor who has experience treating both infections.
Sofosbuvir can be used
by people with all stages of liver disease including compensated and
decompensated cirrhosis. However, it works better for people with less advanced
liver damage. Data on safety and efficacy in decompensated cirrhosis have not
yet been published. People with chronic hepatitis C who are awaiting or have
received a liver transplant tolerate sofosbuvir better than older medications.
How is sofosbuvir taken?
Sofosbuvir is taken as
a single pill once daily with food. It is not effective if taken alone and this
can lead to drug resistance.
Length of treatment
People with HCV
genotype 1, 4, 5 or 6 should take sofosbuvir with weekly pegylated interferon
injections and twice-daily ribavirin pills for 12 weeks. Those who cannot use
interferon can take sofosbuvir plus ribavirin alone for 24 weeks.
People with HCV
genotype 2 should take sofosbuvir with ribavirin alone for 12 weeks. Genotype 3
is harder to treat, so these patients should either extend sofosbuvir plus
ribavirin to 24 weeks, or take sofosbuvir with both pegylated interferon and
ribavirin for 12 weeks.
Recommended uses for
people with HIV and HCV co-infection are the same as for HIV-negative people. Chronic
hepatitis C patients who are awaiting a liver transplant should take sofosbuvir
plus ribavirin, without interferon, until the transplant takes place.
How effective is sofosbuvir?
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 history. People with liver cirrhosis do not respond as well
as those with mild or moderate liver fibrosis. People who are new to treatment
have a better chance of being cured than those with little or no response to
factors that traditionally predict poor response to interferon-based therapy do
not make as much difference with interferon-free treatment. These factors may
be overcome by longer treatment or by adding another direct-acting antiviral
Sofosbuvir treatment response
People who experience
a rapid drop in HCV viral load soon after starting treatment are more likely to
be cured. People with sustained virological response, who still have
undetectable viral load 12 weeks after finishing treatment (known as 'SVR12'),
are considered cured.
A clinical study
called NEUTRINO tested sofosbuvir plus pegylated interferon and ribavirin for
12 weeks for previously untreated people with HCV genotypes 1, 4, 5 or 6
(mostly 1). The cure rate was 91% at 12 weeks post-treatment.
Sofosbuvir has not been well studied
in treatment-experienced people with genotypes 1, 4, 5 and 6. In fact, there are few data at all for genotypes 5
The FISSION study
looked at previously untreated people with HCV genotypes 2 or 3. Overall, 67%
of people taking sofosbuvir plus ribavirin for 12 weeks were cured - the same as the sustained response rate for
people taking pegylated interferon and ribavirin for 24 weeks. However, sofosbuvir/ribavirin cured 95% of
people with genotype 2, compared with 56% of those with genotype 3. For
genotype 3 patients with cirrhosis, the cure rate fell to just 34%.
The FUSION trial
looked at previously treated people with genotypes 2 or 3 (mostly prior
relapsers) who took sofosbuvir plus ribavirin for 12 or
16 weeks. 82% of genotype 2 patients and 30% of genotype 3 patients were cured
with 12 weeks of treatment. People with genotype 3, and especially those with
cirrhosis, did better with 16 weeks.
The VALENCE trial
showed that 24 of weeks of sofosbuvir/ribavirin works best against genotype 3,
raising the cure rate to 93% for previously untreated people and 77% for those
being retreated. Response rates were high even for previous non-responders and
people with cirrhosis using the longer duration.
The PHOTON-1 study
tested sofosbuvir plus ribavirin for people with HIV and HCV co-infection. The cure
rate was about 75% for people with HCV genotype 2 or 3 treated for 12 weeks, or
those with genotype 1 treated for 24 weeks.
Finally, a study of hepatitis C patients
with liver cancer awaiting a liver transplant found that 62% were cured, having
undetectable viral load in the new liver at 12 weeks post-transplant.
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.
Experimental use of sofosbuvir
Other studies have
shown that sofosbuvir works even better in combination with experimental
direct-acting antivirals now in development. All-oral regimens with neither interferon
nor ribavirin will become an option as these new drugs are approved.
The ION studies showed
that sofosbuvir plus ledipasvir, an experimental HCV NS5A inhibitor, cured 90
to 100% of previously untreated and treatment-experienced people with HCV
genotype 1, including those with cirrhosis. These two drugs are being developed
as a once-daily co-formulation, or combination pill.
In the SYNERGY study,
95 to 100% of hard-to-treat genotype 1 patients were cured with
sofosbuvir/ledipasvir taken alone for 12 weeks, or a triple combination adding
a third direct-acting antiviral for just six weeks.
The COSMOS study
showed cure rates above 90% for sofosbuvir plus the next-generation HCV
protease inhibitor simeprevir (already approved in the US) taken for
12 weeks. Similar good response rates have been seen in studies of sofosbuvir combined
with other experimental drugs including daclatasvir.
What are the side-effects of sofosbuvir?
generally well tolerated with no known specific side-effects of its own. The
most common side-effects seen in people taking sofosbuvir with ribavirin or
pegylated interferon/ribavirin are fatigue, headache, nausea and insomnia.
ribavirin can cause other side-effects including muscle and joint aches,
itching, depression, anaemia (low haemoglobin level) and neutropenia (low white
blood cell count). Ribavirin can also cause birth defects, so it should not be
used by pregnant women or their male partners.
Does sofosbuvir interact with other drugs?
interact with certain drugs processed by a protein known as 'P-gp', including
some TB medications, psychiatric drugs and herbal products containing St. John's wort.
Information about specific drug interactions is available online at www.hep-druginteractions.org.
How can I get sofosbuvir?
available by prescription in European Union countries to treat all genotypes of
hepatitis C. Ask your GP or liver specialist if sofosbuvir may be a good
When to start
treatment will depend on a number of factors, including severity of liver
damage (as determined by FibroScan or
a liver biopsy). People with mild liver disease may be able to wait, and new
hepatitis C medications that can be used in interferon-free treatment are
coming soon. However, the decision to wait must take into account how fast your
liver disease might progress – which is hard to predict – and how soon these new treatments will be
approved in your country.