An investigational oral hepatitis C virus (HCV) polymerase inhibitor VX-222 developed by Vertex Pharmaceuticals has been seen reducing the viral load considerably.
A phase 1b clinical trial of VX-222 showed that the drug was well-tolerated, with all adverse events being mild to moderate in severity.
Dosing with VX-222 for three days resulted in a greater than 3 log10 reduction in HCV RNA across all four of the VX-222 dosing groups.
No serious adverse events or treatment discontinuations were reported in the Phase 1b trial.
“In this Phase 1b clinical trial, treatment with VX-222 for three days resulted in a reduction in viral load across all the dose groups studied,” said Maribel Rodriguez-Torres, M.D., Medical Director of Fundacion de Investigacion de Diego in Puerto Rico.
The results from this trial support the Phase 2 proof-of-concept clinical trial of VX-222 dosed in combination with Vertex’s lead investigational HCV protease inhibitor telaprevir, which is expected to complete enrollment in the second quarter of 2010, Vertex said in a press release.
The clinical results from the Phase 1b viral kinetic portion (Part A) of a two-part Phase 1b/2a clinical trial of VX-222.
This double-blind, randomized placebo-controlled, dose-ranging Phase Ib clinical trial was designed to evaluate the safety, tolerability, pharmacokinetics and effect on viral kinetics of four doses of VX-222, including doses of 250 mg every 12 hours (BID), 500 mg BID, 750 mg BID, and 1,500 mg once a day (QD), or placebo.
In the trial, VX-222 was administered as monotherapy for three days. Patients then had the option to receive treatment with pegylated interferon (Peg-IFN) and ribavirin (RBV) for up to 48 weeks.
Thirty-two treatment-naive patients with chronic genotype 1 HCV infection were enrolled in the trial, including six patients in each dose group who received 250 mg of VX-222 BID, 500 mg of VX-222 BID, 750 mg of VX-222 BID, and 1,500 mg of VX-222 QD.
Treatment with VX-222 resulted in mean reductions in plasma HCV RNA of greater than 3 log10 across the four VX-222 dose groups.
An increasing dose response was observed across the four dose groups, with the results in the 500 mg, 750 mg and 1,500 mg dose groups being very similar.
The mean HCV RNA decline achieved after three days of dosing with 250 mg BID, 500 mg BID, and 750 mg BID of VX-222 was 3.1 log10, 3.4 log10, and 3.2 log10, respectively.
The mean HCV RNA decline achieved after three days of dosing with 1,500 mg QD of VX-222 was 3.4 log10. In the patients receiving placebo, no notable decline in HCV RNA was observed. Similar viral declines were observed for patients infected with genotype 1a and 1b.
The results of Part A of this trial are consistent with the findings from a previously conducted three-day, five-patient viral kinetic study of VX-222 dosed as 750 mg BID.
Part B of the study will evaluate 12 weeks of VX-222 dosed in combination with pegylated-interferon and ribavirin in treatment-naive HCV patients.
Part B of this trial is expected to begin enrolling patients in the second quarter.
In March 2010, Vertex announced plans to initiate the first clinical trial evaluating VX-222 dosed in combination with the investigational HCV protease inhibitor telaprevir. The trial will evaluate the safety and sustained viral response rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222.
Vertex expects to complete enrollment in this trial in the second quarter of 2010 and expects interim clinical data from this trial in the second half of 2010.
VX-222 is a small molecule non-nucleoside inhibitor of HCV NS5B polymerase. Vertex obtained VX-222 as part of its acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide rights to VX-222.
Telaprevir is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naive and treatment-failure patients.
Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America.
Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and other countries.
Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
What is hepatitis C?
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of people with the disease.
Chronic HCV infection affects up to 3.9 million individuals in the United States and is spread through direct contact with the blood of infected people.
Though many people with HCV infection may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.
Chronic HCV can lead to serious liver problems, including liver damage, cirrhosis, liver failure, or liver cancer.
The majority of patients infected with HCV were born between 1946 and 1964, accounting for two of every three chronic HCV cases.
The majority of patients infected with HCV are unaware of their infection.
Over the next 20 years, total annual medical costs for patients with HCV infection are expected to more than double, from $30 billion today to approximately $85 billion.
Current therapies for HCV typically result in a sustained viral response in about half of patients with genotype 1 HCV, the most common strain of the virus.
If treatment is not successful and patients do not achieve an SVR, they remain at risk for progressive liver disease.
The risk of liver failure, liver cancer or death following unsuccessful HCV treatment was assessed at 23% after 4 years, and 43% after 8 years.
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs. Vertex’s product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.