Harvoni is a medication
used to treat hepatitis C. It is a combination pill containing sofosbuvir (sold
separately as Sovaldi) plus ledipasvir. It was approved in Europe in
November 2014 for treatment of adults with genotype 1 or 4 chronic hepatitis C,
and for some people with genotype 3. Harvoni is also approved for use in
children aged 3 years and over.
For most people, Harvoni can be used without ribavirin. Some
people with harder-to-treat disease may do better if they add ribavirin.
Successful treatment reduces the risk of long-term complications of hepatitis C
such as liver cancer or needing a liver transplant.
How does Harvoni work?
Harvoni 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. Ledipasvir 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 Harvoni?
Harvoni is indicated for
use by adults with chronic hepatitis C, meaning infection lasting more than six
months. It is approved for people with HCV genotypes 1 or 4, and for some
people with genotype 3. Genotype 1 is the most common type in Europe.
Harvoni 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’).
Harvoni 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 Harvoni can be used
with most HIV medications. People with HIV and HCV co-infection who want to
take Harvoni should do so under the care of a doctor who has experience
treating both infections.
Harvoni 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 for or have received a liver transplant.
How is Harvoni taken?
Harvoni is taken as a
single pill once daily with or without food. The length of treatment, and
whether Harvoni should be taken with ribavirin, depends on HCV genotype,
amount of liver damage and prior treatment history. The dose of Harvoni
in children depends on weight. Children weighing 35kg or more take the full
adult dose. Children weighing 17-35kg take one half-dose tablet (45mg/200mg).
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Combination
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Duration
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Genotype
1, 4, 5, 6
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12 weeks (no cirrhosis, no previous treatment) (8
weeks may be an option for genotype 1 if previously untreated)
12 weeks (no cirrhosis, previously treated)
24 weeks (no cirrhosis, previous treatment, lack
of future options)
24 weeks (cirrhosis or post-transplant with
cirrhosis)
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Genotype
1,4,5,6
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With ribavirin
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12 weeks (no cirrhosis, previous treatment or
post-transplant)
12 weeks (cirrhosis, including decompensated
cirrhosis)
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Genotype 3
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With ribavirin
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24 weeks (cirrhosis and/or previous treatment)
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People with genotype 2 should use sofosbuvir (Sovaldi) plus
ribavirin, not the Harvoni combination pill.
Recommended uses for people with HIV and HCV co-infection are the same
as for HIV-negative people.
How effective is Harvoni?
Harvoni 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 advanced liver disease may not respond as well as those with
mild or moderate liver fibrosis. People who are new to treatment might have a
better chance of being cured than those who did not respond to prior treatment.
These factors may be overcome by longer treatment or by adding ribavirin, which
helps prevent relapse.
Harvoni treatment response
People with sustained virological response, who still have undetectable HCV
viral load 12 weeks after finishing treatment (known as ‘SVR12’), are
considered cured.
The phase 3 ION studies showed that the drugs in Harvoni,
sofosbuvir plus ledipasvir, cured 94 to 100% of previously untreated and
treatment-experienced people with HCV genotype 1.
ION-1 showed that previously untreated people with or without liver
cirrhosis had high cure rates with 12 weeks of treatment. ION-2, a study of
previously treated people, found that 24 weeks worked better than 12 weeks for
those with cirrhosis. ION-3 showed that 94% of previously untreated people
without cirrhosis were cured in just 8 weeks. In all of these studies, adding
ribavirin did not improve cure rates.
The ERADICATE trial found that Harvoni without ribavirin for 12
weeks cured HCV in 98% of previously untreated people with HIV and HCV
co-infection who had HCV genotype 1 and no cirrhosis.
In the SYNERGY study, 95% of participants with HCV genotype 4 – which
included previously untreated and treatment-experienced people with and without
cirrhosis – were cured using Harvoni without ribavirin for 12 weeks.
The SOLAR-1 trial showed that Harvoni plus ribavirin taken for 12
or 24 weeks cured 87 to 89% of people with HCV genotype 1 or 4 and
decompensated cirrhosis. The same regimen led to early sustained response
(‘SVR4’) for more than 95% of liver transplant recipients with advanced
fibrosis or compensated cirrhosis, although response rates were lower for
people with decompensated liver disease.
The ELECTRON-2 study showed that Harvoni plus ribavirin for 12
weeks cured 100% of previously untreated people with HCV genotype 3, but the
cure rate fell to 64% without ribavirin.
Harvoni’s 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 Harvoni?
Harvoni is generally well
tolerated. The most common side effects seen in clinical trials were fatigue
and headache. The drugs in Harvoni have not been tested in pregnant or
breastfeeding women. Ribavirin can cause side effects including anaemia. It can
also cause birth defects, so it should not be used by pregnant women, women
planning to conceive, or their male partners.
Does Harvoni interact with other drugs?
The drugs in Harvoni can interact with certain drugs processed by
a protein known as ‘P-gp’, including some tuberculosis (TB) medications,
psychiatric drugs and cholesterol-lowering drugs. Harvoni should not be
taken with rosuvastatin (Crestor) or herbal products containing St
John's wort.
Harvoni 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. Harvoni should be used with caution when taken with HIV
protease inhibitors. Information about other specific drug interactions is
available online at www.hep-druginteractions.org.
Factsheet reviewed March 2022.