Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat is stored in the liver. This build-up of fat is not caused by heavy alcohol use. Two types of NAFLD are simple fatty liver and non-alcoholic steatohepatitis (NASH). Simple fatty liver and NASH are two separate conditions, and people typically develop one or the other. NASH is characterized by inflammation of the liver (hepatitis) and liver cell damage. Inflammation and liver cell damage can cause scarring (fibrosis) of the liver leading to cirrhosis. NASH may lead to other complications such as decompensated cirrhosis of the liver, in which the liver no longer functions, and liver cancer.
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.
Etrolizumab is a new monoclonal antibody (an immune protein) delivered by subcutaneous injection. The treatment works by targeting molecules called integrins to control the immune response and prevent the accumulation of immune molecules, which cause inflammation in individuals with a form of ulcerative colitis where inflammation is not mediated by a signalling protein called tumour necrosis factors (TNF) alpha (‘non-TNF-α’) and who are therefore intolerant to TNF blockers. This represents a new target group as current therapies focus mainly on anti-TNF inflammation. In one study, etrolizumab showed a greater reduction of intestinal lymphocyte infiltration in comparison to standard treatment.