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Cenicriviroc + tropifexor is an investigational oral combination therapy developed for the treatment of nonalcoholic steatohepatitis (NASH) and liver fibrosis. The combination brings together two agents with distinct mechanisms of action: - Tropifexor is a highly potent agonist of the farnesoid X receptor (FXR), a nuclear receptor involved in bile acid regulation and metabolic pathways relevant to NASH. - Cenicriviroc is a potent and selective antagonist of chemokine receptors CCR2 and CCR5, which are implicated in inflammation and fibrogenesis. The rationale for combining these drugs is to target both metabolic dysfunction (via FXR agonism) and inflammatory/fibrotic pathways (via CCR2/CCR5 antagonism). In phase 2b clinical trials, this combination was evaluated against monotherapies for safety and efficacy. Results showed that while the safety profile was similar across groups with no new signals identified, there was no substantial incremental efficacy observed on key endpoints such as ALT reduction or histological improvement compared to monotherapy[1][3][7]. The most common adverse event reported was pruritus.
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