FDA Approved Drug for Hepatitis C: New Fixed-Dose Combination - Sofosbuvir, Velpatasvir and Voxilaprevir

The treatment armamentarium for hepatitis C has seen a recent addition - a fixed-dose combination of sofosbuvir, velpatasvir and voxilaprevir, which has been approved by the U.S. Food and Drug Administration for the treatment of chronic hepatitis C without cirrhosis or with mild cirrhosis in previously treated patients. 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), and 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.

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 and ledipasvir.

Last 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.

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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.

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References:

1. FDA approves Vosevi for Hepatitis C - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567467.htm)
2. 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

Source-Medindia