Hepatitis C - isatoribin
It is estimated that about 170 million people around the world are infected with the hepatitis C virus. Of these, 10- 20% are expected to develop cirrhosis of the liver and 1-5% liver cancer.
It is estimated that about 170 million people around the world are infected with the hepatitis C virus. Of these, 10- 20% are expected to develop cirrhosis of the liver and 1-5% liver cancer.
Although in most cases the virus can be cleared from the body with agents such as interferons and therapeutic vaccines, these do not always work, and significant side-effects can result.
A new potential treatment, isatoribine, was discovered by ICN Pharmaceuticals and is being developed by Anadys Pharmaceuticals.1 It is an agonist of toll-like receptor 7, which is one of a group of pathogen recognition receptors that initiates immune response by the release of cytokines, as well as the activation of pathways and enzymes that destroy intra-cellular pathways. They also activate immature dendritic cells.
The small molecule drug was given to 32 patients with chronic hepatitis C infection in an open label dose escalation proof of concept Phase I study.2 It was given as an intravenous infusion, once a day in doses between 200 and 800mg, or 400mg twice a day for a week, or 800mg twice a day three times a week for two weeks. Adverse events were mild or moderate, including joint pain, headache and insomnia. The flu-like symptoms that are common in direct cytokine therapy were not widespread. Daily doses of 800mg significantly reduced plasma HCV RNA levels.
An open label Phase I trial has also been carried out on the orally available prodrug derivative ANA-975. Ascending single doses of 400, 800 and 1200mg were given to healthy volunteers, and it was found to have excellent bioavailability and to be rapidly converted into isatoribine in the plasma. This prodrug is being developed in collaboration with Novartis and undergoing investigation as a potential treatment for hepatitis B infection.