Primary sclerosing cholangitis (PSC) is an uncommon chronic liver disease. In PSC the bile ducts (small tubes which allow bile to flow from the liver to the small intestine where it helps with digestion) become inflamed and scarred causing them to narrow and block. This causes bile to build up in the liver which slowly damages and scars the liver. The cause of PSC is unknown but potential causes may originate from genetics, immune system problems and bacteria or viruses. The main symptoms of PSC include itching, tiredness and yellowing of the skin and eyes. There is no cure for PSC and there are few treatments available. This means many people with PSC will require a liver transplant.
Timolumab is currently being developed to treat PSC. Timolumab is given by injection into the vein which blocks a molecule called VAP-1 from working. VAP-1 helps immune cells enter areas of inflammation (such as the bile ducts in PSC) where they can further contribute to inflammation. By blocking this process, timolumab has the potential to prevent some of the inflammation in PSC and slow the progress of the disease. Therefore if licensed, timolumab will offer an additional treatment option for patients with PSC who currently have few effective therapies available.
Selonsertib is an investigational oral small molecule inhibitor of ASK1, a protein that mediates inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH. NASH currently has no effective treatment apart from lifestyle interventions. If licensed, selonsertib will offer a new treatment option for NASH as no effective pharmacological therapies currently exist.