Hepatitis C virus (HCV) is a viral infection of the liver that causes both acute and chronic infection. In June 2022 the World Health Organization estimates that 58 million people worldwide have chronic HCV infections. Chronic HCV infection can lead to fibrosis (scarring), cirrhosis, liver failure, and liver cancer. WHO estimated that in 2019 approximately 290,000 people died from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer).
We believe the future of the hepatitis C market belongs to direct acting antiviral drugs (DAAs) that are effective against all or multiple hepatitis C genotypes, have a high barrier to resistance, and have a short treatment duration. The best therapies are cocktails of several DAAs. Our focus is on developing what are now called ultrashort treatment regimens from 2 to 6 weeks in length. Such a combination treatment with different classes of DAAs has the potential to change the paradigm of treatment for HCV with its efficacy, higher barrier to viral resistance, improved compliance, and shorter duration of treatment. These strategies could allow us to expand and broaden our portfolio in the HCV antiviral therapeutic area globally and could lead to a high and fast cure rate, to improve compliance, and to simplified treatment duration. No competing company has yet developed a short-duration HCV treatment of 4 weeks or less successfully with a high (>95%) sustained virologic response (SVR) at week 12.
To learn more about hepatitis C, please visit the information page at the Center for Disease Control and Prevention (CDC).
CC-31244 - Pan-genotypic NS5B NNI
CC-31244, a non-nucleoside polymerase inhibitor (“NNI”), is a potential best-in-class pan-genotypic inhibitor of NS5B polymerase for the treatment of hepatitis C infection. It has the potential to be an important component in an all-oral ultra-short duration HCV combination therapy.
U.S. Phase 2a Study - University of Maryland
In January 2019, we announced safety and preliminary efficacy data from a triple regimen, U.S. Phase 2a study evaluating CC-31244 and Epclusa® (sofosbuvir/velpatasvir) for the ultra-short treatment of HCV infected individuals.
The open-label U.S. Phase 2a study was designed to evaluate the safety, tolerability, and preliminary efficacy of CC-31244 and Epclusa, an approved 12-week therapy for HCV developed by Gilead Sciences, Inc., in 12 subjects with treatment-naïve HCV genotype 1. Subjects received oral 400 mg of CC-31244 and Epclusa for 2 weeks. Following this, the subjects continued Epclusa treatment alone for another 4 weeks. All subjects completed the 6-week treatment regimen. The treatment was well tolerated with no study discontinuations due to adverse events. Eight of 12 subjects achieved the primary efficacy endpoint of sustained virologic response at 12 weeks after completion of treatment (SVR12). SVR12 is defined as undetectable virus in blood 12 weeks after completion of treatment and is considered a virologic cure.
In November 2019, we announced new data demonstrating positive results from our triple regimen, U.S. Phase 2a study evaluating CC-31244 and Epclusa for the ultrashort treatment of HCV infected individuals. Results from the Phase 2a study demonstrated that eight of 12 (67%) patients achieved primary endpoint of sustained virologic response (SVR12), which is considered a cure, using only 6 weeks of Epclusa’s therapy combined with only 2 weeks of CC-31244. Patients who achieved SVR had significantly higher frequencies of terminally differentiated effector memory CD8+ T cells compared with those who relapsed at both baseline and at end-of-6-week treatment. At the same time, the frequency of naïve CD8+ T cells was lower while the frequency of effector memory CD8+ T cells was higher in SVR patients; however, these differences were not statistically significant. NK cell cytotoxic phenotypes determined by measuring expression of TRAIL and CD107a also did not differ between SVR and relapse patients, unlike another study that evaluated a different regimen for 12 weeks.
We are in ongoing partnership discussions for further clinical development of CC-31244.
For additional information about the U.S. Phase 2a study of CC-31244 for the treatment of viral hepatitis C, please visit ClinicalTrials.gov and reference identifier NCT03501550.