It is estimated that in the USA alone, some 4 million people have been infected with Hepatitis C with 2.7 million suffering from chronic infection. Worldwide, 180 million people are infected, with an estimated 30 million infected in China. Hepatitis C virus (HCV) causes inflammation of the liver, which may lead to fibrosis and cirrhosis, liver cancer and, ultimately, liver failure. Despite recent advances with direct-acting antiviral drugs (DAAs) for HCV, treatment challenges remain with specific patient populations. Length of treatment, and cost of drugs, remain hurdles in the HCV treatment arena.
Biotron’s HCV program is focused on developing drugs to target the HCV p7 protein. HCV p7 is highly conserved and present in all 6 clades, with a critical role in virus assembly and release, and is a potential new target for therapeutic intervention. BIT225 is a novel small molecule viral assembly inhibitor that targets p7 and is in development for treatment of chronic HCV infection.
- Viral assembly inhibitor targeting HCV p7 protein
- Pan-genotypic activity in vitro in the HCV infectious clone assay
- Synergy with other anti-HCV drugs in vitro
- High barrier to antiviral resistance in vitro
- Comprehensive preclinical safety and toxicology data package
- Clinical antiviral efficacy against genotypes 1 and 3
- BIT225 treatment is associated with faster viral clearance in treated patients.
A Phase 1a safety trial (BIT225-001) in healthy volunteers was completed in late 2007. A Phase 1b, repeat-dose monotherapy study (BIT225-003) in HCV-infected patients was completed in late 2009. The results demonstrated that BIT225 showed antiviral efficacy against genotype 1-3, significantly reducing viral loads compared to placebo, and that the drug was well tolerated. The antiviral kinetics suggested that efficacy increased with treatment duration.
The Phase 2a, 28-day, repeat-dose, combination trial (BIT225-005) of BIT225 with standard of care (pegylated interferon and ribavirin; IFN/RBV) in treatment-naïve, genotype 1 HCV-infected patients was completed in August 2011. BIT225 demonstrated good anti-HCV activity, with treatment-naïve, HCV genotype 1 patients receiving BIT225 in addition to IFN/RBV having significantly lower viral loads than those receiving IFN/RBV alone at the conclusion of dosing. The three-month complete EVR in patients who received BIT225 +IFN/RBV was 87%, compared to 63% in the IFN/RBV control group. The 48-week data extends the previous three-month data, demonstrating BIT225 continued to provide additional benefit to patients after the conclusion of dosing, with 100% SVR in patients who received BIT225 (400 mg) +IFN/RBV, compared to 75% in the IFN/RBV control group.
A Phase 2, 3-month repeat-dose, combination trial (BIT225-008) of BIT225 with IFN/RBV in treatment naïve, genotype 1 and 3 patients is in progress, with final data expected in early 2016.
Due to BIT225’s dual activity against HIV-1 and HCV it is uniquely placed as a potential treatment in HIV-1/HCV co-infected patients. The proportion of patients infected with both HIV-1 and HCV is significant, with 25 – 40% of HIV-1 patients in the USA also infected with HCV. Drug-drug interactions with some classes of new HCV drugs can limit treatment options in this group of patients.
Biotron initiated a Phase 2 trial (BIT225-006) of BIT225 in combination with IFN/RBV in HIV-1/HCV co-infected patients in November 2012. All HCV genotype 3 subjects who completed 28 days treatment with BIT225 plus standard treatment with IFN/RBV achieved SVR12.
BIT225 has the following advantages:
- First-in-class, new mode of action drug
- Potential to be combined with other anti-HCV drugs to reduce treatment times and improve outcome, especially in HCV genotype 3 patients.