Editorial: targeting aberrant hepatic inflammation for treatment of non‐alcoholic steatohepatitis—authors' reply

We thank Drs Muthiah and Siddiqui for their concise summary of our article,1,2 and their clinical interpretation of the results. Compared to other drugs under clinical development, namodenoson has a considerable advantage of having an excellent safety profile, as was demonstrated in the phase 2a study as well as in other studies.2,3 The excellent safety profile stems from our scientific approach which was based on the observation that the A3 adenosine receptor target is overexpressed in pathological but not normal body cells, and therefore normal body cells are refractory to the effect of the drug.4 Indeed, in the phase 2a study, the antiinflammatory effect of namodenoson has been manifested by a decrease in ALT and AST and upregulation of adiponectin during the 12 weeks of treatment with namodenoson. Additional parameters such as Fib4 and FAST improved in a significant manner in the high dose of 25 mg namodenoson administered twice daily, whereas other parameters like the CAP Score ≥331 and body weight decreased numerically, although no statistical significance was observed.2 The results from the phase 2a study that demonstrate a clear trend of improvement during the 12 weeks of treatment were used to design the phase 2b randomised, doubleblind, placebocontrolled study, in which the inclusion criteria are based on histopathology of liver biopsies and patients are treated for 36 weeks. The protocol for such a phase 2b study has already been developed by the company (NCT04697810, Figure 1) and approved by the relevant institutional review boards. Patient enrolment will commence shortly.