zifcasiran

Zifcasiran is an investigational, intravenously administered, tumor-directed small interfering RNA (siRNA) therapeutic that selectively targets hypoxia-inducible factor 2 alpha (HIF-2α) mRNA to reduce HIF-2α synthesis in tumor cells. It was developed by Arrowhead Pharmaceuticals for the treatment of advanced clear cell renal cell carcinoma and other HIF-2α–driven solid tumors, aiming to interrupt the VHL/HIF2α oncogenic pathway more proximally than VEGF-directed agents and as a potential complementary strategy to small-molecule HIF-2α inhibitors. In a first-in-human phase 1 study in heavily pretreated clear cell renal cell carcinoma, zifcasiran demonstrated tumor uptake, reduction of HIF-2α expression, evidence of antitumor activity, and a toxicity profile notable for fatigue, dizziness, dyspnea, nausea, and treatment-emergent neuropathic events including peripheral neuropathy and CIDP.[1][3][8][10]

Other names

ZIFCASIRAN sodium