Gilead's Vosevi, the World’s First Once-Daily Single-Tablet Triple-Combination HCV Therapy, Approved in China

By Baihuawen

Hepatitis C is known as the “silent killer.” Unlike hepatitis B, hepatitis C has an insidious onset, often presenting with no symptoms at the time of infection, which leads patients to overlook it and thereby increases the risk of disease progression to liver cirrhosis and liver cancer. It is estimated that nearly 10 million people in China are infected with the hepatitis C virus (HCV), accounting for 5.4% of the global infected population. The hepatitis C virus is primarily classified into six genotypes. In China, more than 50% of patients have genotype 1b, while the remainder have genotypes 2, 3, or 6, with varying prevalence across different regions.

On December 18, Gilead’s hepatitis C drug Vosevi was approved for marketing in China. Vosevi is a fixed-dose combination regimen comprising sofosbuvir, velpatasvir, and voxilaprevir, and is referred to by industry insiders as “Gilead’s Fourth-Generation Therapy.”

Vosevi was approved by the FDA on July 18, 2017, for the treatment of adult patients with genotype 1–6 hepatitis C virus (HCV) infection, with mild cirrhosis or without cirrhosis. It is the first once-daily, single-tablet HCV regimen approved for use in patients who have previously been treated with a sofosbuvir-containing regimen or an NS5A inhibitor-containing regimen. In China, Vosevi was included in the “First Batch of Clinically Urgent Overseas Drugs” in March 2019. In June 2019, Gilead Sciences submitted the marketing application for this drug, and it took six months from submission to approval.

Gilead Sciences is a leader in the field of hepatitis C. Sovaldi (sofosbuvir), known as "Gilead's First Generation," is the world’s first NS5B polymerase inhibitor. By potently inhibiting HCV replication, this drug has enabled the cure of hepatitis C. In 2017, Gilead Sciences entered the Chinese market, and in the same year, sofosbuvir tablets were approved for marketing in China, becoming the country’s first direct-acting antiviral (DAA) drug covering all genotypes of chronic hepatitis C.

In May and November 2018, Gilead Sciences successively launched its third-generation hepatitis C drug, sofosbuvir/velpatasvir tablets, and its second-generation drug, ledipasvir/sofosbuvir tablets, in China. Currently, both new drugs have been included in the Class B list of the 2019 National Reimbursement Drug List through price negotiations, although the specific reimbursement standards remain confidential.

The safety and efficacy of Vosevi were confirmed in two Phase III studies involving 750 patients with hepatitis C. The first study evaluated the efficacy and safety of Vosevi versus placebo in patients with genotype 1 hepatitis C who had previously failed treatment with an NS5A inhibitor. Patients with genotypes 2–6 also received Vosevi for 12 weeks.

Study 2 compared the efficacy of 12 weeks of Vosevi treatment versus sofosbuvir (NS5B) plus velpatasvir (NS5A) and placebo in patients with genotype 1–3 hepatitis C who had previously failed treatment with sofosbuvir (NS5B).

The results showed that 96% to 97% of patients had no detectable virus in their blood 12 weeks after completing treatment, achieving a cure. Adverse reactions associated with Vosevi treatment were related to the viral genotype, with the most common adverse reactions including headache, fatigue, diarrhea, and nausea.