HCV is a blood-borne, positive sense, ssRNA virus, primarily infecting cells of the liver. HCV is a leading cause of chronic liver disease and liver transplants and spreads via blood transfusion, hemodialysis and needle sticks. In the United States, injection drug use accounts for approximately 60% of all new cases of HCV. Diagnosis of HCV is made through blood tests, including molecular tests that allow for the detection, quantification and analysis of viral genomes and the classification of an infection into specific viral genotypes. Hepatitis C becomes chronic Hepatitis C in 75% to 85% of cases, with an incubation period lasting from two to 26 weeks.
HCV is classified into seven genotypes and 67 subtypes, with genotype 1 being responsible for more than 70% of HCV cases in the United States. Patients with HCV are also classified by liver function status: compensated cirrhosis (liver scarring) denotes those patients that do not yet have impaired liver function, while decompensated cirrhosis describes patients with moderate to severe liver function impairment.
According to the WHO, an estimated 58 million people globally have chronic HCV infection, with about 1.5 million new infections occurring per year. Approximately 290,000 people die every year from HCV-related liver diseases, with the majority of death resulting from cirrhosis and hepatocellular carcinoma (HCC – primary liver cancer).
Despite significant advances in treatment beginning in 2013, there remains a large, underserved, HCV patient population that continues to grow dramatically in the United States. While a portion of this increase results from increased diagnosis of HCV that began following the 2013 CDC issuance of guidelines for screening of all Americans born between the years 1945 and 1965, a large portion of this increase in incidence is attributable to the opioid crisis, IV drug use and HCV reinfection. The United States HCV prevalence is expected to continue to remain steady over the coming years as rising HCV incidence offsets the number of new patients treated.
It is estimated that a substantial global market for HCV therapeutics will exist to 2050 and beyond. In 2021, the HCV market remained large with global sales approaching $4 billion of which approximately 50% are attributable to the United States. In the United States, HCV prevalence is anticipated to remain steady over the coming years as rising HCV incidence offsets the number of new patients treated.
A combination of bemnifosbuvir and ruzasvir has the potential to offer a differentiated short duration, pan-genotypic protease-sparing regimen for HCV-infected patients with or without cirrhosis.