Like the hepatitis B
virus, the hepatitis C virus spreads through blood and other contaminated body
fluids, and affects the liver resulting in permanent damage (cirrhosis
sometimes even liver cancer. The virus has 6 genetic variants - referred to as
genotypes 1-6, with the genotype 1 being most common among Americans.
‘A new fixed-dose combination of sofosbuvir, velpatasvir and voxilaprevir has been approved by the US FDA for the treatment of hepatitis C in patients without or with mild cirrhosis who had been treated earlier.’
Since the discovery of
the hepatitis C virus less than three decades ago in 1989, several treatments
have been approved in quick succession at a remarkable rate. The initial treatments of ribavirin and
interferons led to the approval of the direct-acting antivirals which include
the protease inhibitors like boceprevir, telaprevir and simprevir, the
polymerase inhibitor sofosbuvir, and the NS5A inhibitor drugs like daclastavir
year, we published reports on the successful trials on two combinations - the
sofosbuvir-velpatasvir combination, and the
elbasvir - grazoprevir combination,
which later led to
their approval by the US FDA.
The new combination pill
contains 400mg of sofosbuvir and 100mg each of velpatasvir and voxilaprevir. It can be used in those who have not
responded to treatment with sofosbuvir (patients with genotypes 1a or 3) or
NS5A inhibitor (patients with any genotypes).
The approval of the combination comes
following the completion of two Phase 3 trials that evaluated the treatment in
patients without cirrhosis or with mild cirrhosis.
- Patients included
in the POLARIS-1 study harbored the hepatitis C genotype 1 and had failed
treatment with an NS5A inhibitor drug. These patients either received the
new combination treatment or placebo for a duration of 12 weeks. Patients
who had other genotypes were administered the combination treatment.
- The POLARIS-4
study, also conducted over 12 weeks, included patients with genotypes 1, 2
or 3 who failed to respond to treatment with sofosbuvir but not to an NS5A
inhibitor drug. The new combination treatment was compared to the older
combination of sofosbuvir and velpatasvir.
The patients in both the
trials showed a positive response to the treatment with the new drug
combination. The virus was not detected
in the blood 12 weeks after completion of the treatment in around 96-97 percent
of patients who received the combination.
Side effects of the new
combination noted in the studies included headache, fatigue, diarrhea and
nausea. The percentage of people who discontinued treatment due to side effects
was less than 1 percent.
The new combination
should not be administered in patients who have received the drug rifampin. It
should also not be administered in patients with prior or on ongoing hepatitis
B infection due to the danger of reactivation of the hepatitis B infection.
Thus, the new
combination of sofosbuvir, velpatasvir and voxilaprevir provides an option to
hepatitis C patients who did not respond to the earlier regimens.
- FDA approves Vosevi for Hepatitis C - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567467.htm)
- Bourliere M et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med 2017; 376:2134-2146 DOI: 10.1056/NEJMoa1613512