Arrowhead presents updated data from Phase 2 SEQUOIA study

Arrowhead Pharmaceuticals (ARWR) presented updated results from the Phase 2 SEQUOIA clinical study of investigational fazirsiran for the treatment of liver disease associated with alpha-1 antitrypsin deficiency. The SEQUOIA Phase 2 data are consistent with the promising results from an open-label Phase 2 trial of fazirsiran that were published in The New England Journal of Medicine. Takeda (TAK) and Arrowhead are further investigating fazirsiran in the ongoing pivotal Phase 3 REDWOOD clinical study which is actively recruiting a total of 160 patients. The updated Phase 2 clinical data were presented at the European Association for the Study of the Liver Congress 2023 in an oral presentation titled. Fazirsiran reduced serum Z-AAT concentration in a dose-dependent manner. At week 48, patients receiving 25, 100, or 200 mg fazirsiran achieved serum Z-AAT reductions of 74%, 89%, and 94%, respectively, versus an increase of 9% observed in patients receiving placebo. Fazirsiran significantly reduced liver Z-AAT. Patients receiving 200 mg fazirsiran achieved a least-squares mean percentage difference versus placebo at post-dose biopsy of -141%. Fazirsiran consistently reduced hepatic globule burden. 100% of patients in the pooled fazirsiran treatment group achieved at least a 1-point improvement in PASD-positive globule burden. Fazirsiran treatment reduced histological signs of hepatic inflammation. 42% of patients in the pooled fazirsiran treatment group achieved at least a 1-point improvement in portal inflammation versus 0% in the placebo group. 67% of patients in the pooled fazirsiran treatment group achieved at least a 1-point improvement in interface hepatitis versus 0% in the placebo group. 50% of the pooled fazirsiran treated patients showed at least a 1-point improvement in METAVIR liver fibrosis versus 38% in the placebo group. Fazirsiran has been well tolerated to date. Pulmonary function test results for both fazirsiran and placebo were stable over time with no apparent dose-dependent effects.