FXR is a nuclear receptor that regulates bile acid metabolism and signaling. Activation of the receptor inhibits bile acid synthesis from cholesterol via cytochrome P450 7A1 and increases bile acid conjugation, transport, and excretion. This protects the liver from the potentially harmful effects caused during bile acid accumulation. Tropifexor (Novartis/Pfizer) is a novel, highly potent, non-bile acid FXR agonist. It has demonstrated potent activity in rodent Parkinson’s disease models by measuring the induction of FXR target genes in tissues.
Tropifexor could stand out against the other FXR agonists Ocaliva (obeticholic acid; Intercept Pharmaceuticals) and cilofexor (Gilead) due to its favorable safety profile and lack of reported pruritis. If efficacy is comparable to the aforementioned rivals, which are expected to reach the market earlier, then tropifexor’s cleaner safety and tolerability profile could allow it to emerge as the preferred FXR agonist. In addition, Novartis’s collaboration with Pfizer could overcome tropifexor’s late entry to market as the companies have an abundance of developmental and commercial resources that small biotech companies such as Intercept or Genfit will find difficult to compete with.
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