On June 28 the
US Food and Drug Administration approved Gilead Sciences Epclusa, a new once-daily combination pill containing sofosbuvir
and velpatasvir, for the treatment of adults with hepatitis C virus (HCV)
genotypes 1 to 6 – the first approved oral pangenotypic regimen. While it
is more effective against more types of HCV, Epclusa will cost less than most earlier interferon-free direct-acting
antiviral regimens.
Epclusa contains 400mg of the nucleotide HCV polymerase
inhibitor sofosbuvir (marketed separately as Sovaldi) and 100mg of the novel NS5A inhibitor velpatasvir.
Unlike the
currently available Harvoni
(sofosbuvir/ledipasvir) combination, which is indicated for HCV genotypes 1, 4
and the little-studied 5 and 6, Epclusa
is active against all genotypes.
Glossary
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
Genotype 1 –
the predominant type in the US and Europe – now has several good treatment
options available. Other genotypes are more common elsewhere, including
genotype 3 in India, genotype 4 in the Middle East and North Africa, genotype 5
in South Africa and genotype 6 in parts of Asia. Pangenotypic regimens are
especially welcome in low- and middle-income countries that have high burdens
of hepatitis C, as they can be used without prior genotypic testing.
Epclusa is a complete single-tablet regimen that can be used without ribavirin
for all HCV genotypes. It was approved for previously untreated and
treatment-experienced adults with chronic hepatitis C with or without
cirrhosis. However, people with decompensated cirrhosis (Child-Pugh B or C)
should add ribavirin. Treatment duration is 12 weeks for all people. Epclusa should not be used with certain
other medications (including amiodarone, rifampin, St. John’s wort and
carbamazepine) due to the risk of drug-drug interactions that could cause side-effects or reduce drug concentrations.
Epclusa is
approved to treat people with HIV and HCV co-infection. However, it should not
be used with some antiretrovirals – including efavirenz and tipranavir – and
people taking regimens containing tenofovir should have their kidney function
monitored regularly.
Epclusa was approved
based on clinical trials showing that it produces high rates of sustained
virological response (SVR), considered to be a cure. In the phase 3 ASTRAL trials sofosbuvir/velpatasvir cured 99% of people with chronic hepatitis C with genotypes 1, 2, 4, 5 and
6, and 95% of those with harder-to-treat genotype 3. SVR rates were similar
regardless of prior treatment experience or the presence of compensated
cirrhosis. For people with decompensated cirrhosis, 94% achieved SVR with sofosbuvir/velpatasvir
plus ribavirin in ASTRAL-4. ASTRAL-5 showed a cure rate of 95% for people with HIV/HCV co-infection. Treatment was safe and generally well tolerated, with
few serious drug-related adverse events or drug discontinuations. The most
commonly reported side-effects include headache and fatigue.
Gilead set the list price of Epclusa
at US$74,760 – lower than the retail cost of its earlier Sovaldi ($84,000) and Harvoni
($94,500), not to mention a combination of Sovaldi
plus Bristol-Myers Squibb's $63,000 daclatasvir (Daklinza). The only regimen with a lower list price is Merck's
grazoprevir/elbasvir (Zepatier), at $54,600,
which is only indicated for genotypes 1 and 4.
At this price point and given the good tolerability of
velpatasvir, there appears to be no reason not to use Epclusa rather than sofosbuvir alone for genotype 2, or sofosbuvir
plus daclatasvir or pegylated interferon/ribavirin for genotype 3. However, Harvoni is likely to remain the
preferred regimen for treatment-naive genotype 1 patients without cirrhosis,
who can usually be cured in just 8 weeks – a shorter-duration option that is
not FDA-approved for Epclusa.
To assist eligible patients in the US, Gilead has
added Epclusa to its patient
assistance and co-pay programmes (www.MySupportPath.com).
Gilead notes that it is working with regional business
partners, generic licensing partners, the Medicines Patent Pool and other stakeholders to expand
treatment access worldwide. Epclusa
has already been licensed to eleven manufacturing partners in India that can now
begin producing and distributing a generic version of sofosbuvir/velpatasvir
for 101 low-income countries.