Lynne Taylor

Vertex Pharmaceuticals has announced agreements with GlaxoSmithKline (GSK) and Janssen for the conduct of Phase II proof-of-concept studies of all-oral regimens for the treatment of hepatitis C.

Both studies will involve Vertex’s nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135, an investigational uridine nucleotide analogue pro-drug which is designed to inhibit the replication of HCV by acting on the NS5B polymerase. 

The study agreed with GSK is expected to evaluate safety, tolerability and viral cure rates using a 12-week combination of VX-135 and GSK’s non-structural 5A (NS5A) inhibitor GSK2336805, with and without ribavirin. GSK2336805 is an investigational NS5A replication complex inhibitor being developed by GSK for the treatment of hepatitis C.

The accord with Janssen will evaluate safety, tolerability and viral cure rates using a 12-week combination of VX-135 and Janssen’s protease inhibitor simeprevir (TMC435). Simeprevir is a potent, once-daily investigational drug which is currently in Phase III trials and being jointly developed by Janssen R&D Ireland and Medivir AB. As part of the collaboration with Vertex, Janssen will conduct a drug-drug interaction study with VX-135 and simeprevir, to support the planned initiation of the proof-of-concept study.

The three firms say they will jointly fund the costs associated with the studies, which they plan to initiate in early 2013, pending discussions with regulatory authorities. There are no upfront or milestone payments associated with either of the agreements.

The studies will enrol people who have chronic non-cirrhotic genotype 1 hepatitis C and who have not previously been treated. The study involving GSK2336805 will be conducted in the US by Vertex. Additional information on the studies will be provided upon their initiation, but further clinical development beyond the Phase II proof-of-concept study are not covered as part of either agreement.

Vertex gained worldwide rights to VX-135 through an exclusive licensing agreement signed with Alios BioPharma in June 2011. The agreement also includes a research programme that will focus 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. 

More than 170 million people worldwide are chronically infected with hepatitis C. It is caused by HCV, which is spread through direct contact with the blood of infected people and ultimately infects the liver. The disease can lead to serious and life-threatening 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.

While chronic hepatitis C can be cured, around 60% of patients do not achieve viral cure after treatment with 48 weeks of pegylated-interferon and ribarivin alone, says Vertex.