Vertex Pharmaceuticals Incorporated has entered into a non-exclusive agreement with Bristol-Myers Squibb Company to conduct phase II studies of once-daily all-oral treatment regimens containing Vertex's nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir for the treatment of hepatitis C. As part of the agreement, Vertex plans to conduct two phase II studies of the combination, including an initial study in treatment-naïve people with genotype 1 HCV infection planned for the second quarter of 2013.
Vertex plans to begin a subsequent study in treatment-naïve people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.
"With more than 170 million people infected worldwide, there is a critical need for new hepatitis C medicines that can offer people simpler and more tolerable treatment regimens that provide high cure rates," said Robert Kauffman, MD, Ph.D., senior vice president and chief medical officer at Vertex. "These studies with daclatasvir will provide the first opportunity to evaluate VX-135 as part of all-oral regimens in people with multiple hepatitis C genotypes and in people with cirrhosis."
Under the terms of the agreement, Vertex will conduct two phase II studies of VX-135 in combination with daclatasvir. The first study will enroll approximately 20 non-cirrhotic, treatment-naïve people with chronic genotype 1 HCV infection and is expected to begin in the second quarter of 2013. In the second half of 2013, Vertex plans to conduct a subsequent study in approximately 250 treatment-naïve people with chronic genotype 1, 2 or 3 HCV infection, including those with cirrhosis. Each of these studies is expected to evaluate safety, tolerability, pharmacokinetics and viral cure rates (SVR4 and SVR12) of multiple all-oral regimens of VX-135 and daclatasvir dosed once daily, pending regulatory discussions. Vertex will also conduct co-formulation activities to evaluate the potential for development of a once-daily fixed-dose combination regimen. Further clinical development activities beyond the phase II studies are not covered as part of this agreement.
VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In people with genotype 1, treatment with a 200mg once-daily dose of VX-135 in a 7-day viral kinetic study was well-tolerated, with no discontinuations due to adverse events, and resulted in a 4.54 log10 median reduction from baseline in HCV RNA. Data from a seven-day viral kinetic study of VX-135 in people with genotypes 2, 3 and 4 were consistent with data observed in people with genotype 1 and have been submitted for presentation at a future medical meeting.
Vertex gained worldwide rights to ALS-2200, known as VX-135 in phase II studies, through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research programme.
Daclatasvir is an NS5A replication complex inhibitor that is being extensively studied as a key component of potential DAA-based hepatitis C treatment regimens. Studied in more than 4,100 patients to date, daclatasvir is in phase III development.
Daclatasvir is part of a portfolio of investigational compounds with different mechanisms of action that Bristol-Myers Squibb is developing for the treatment of hepatitis C. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.
Hepatitis C is a serious liver infection caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver. Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain. Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.
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