Arrowhead Pharmaceuticals Reports Underwhelming Data From Inherited Disease Study

Takeda Pharmaceutical Co Ltd TAK and Arrowhead Pharmaceuticals Inc ARWR announced topline results from the Phase 2 SEQUOIA study of fazirsiran (TAK-999/ARO-AAT) for liver disease associated with alpha-1 antitrypsin deficiency (AATD-LD).
Patients receiving 25 mg, 100 mg, or 200 mg of fazirsiran who had baseline fibrosis (n=16) demonstrated a dose-dependent mean reduction in serum mutant alpha-1 antitrypsin protein (Z-AAT) concentration at week 48 of 74%, 89%, and 94%, respectively.
All three doses reduced total liver Z-AAT with a median reduction of 94%.
In addition, PAS-D globule burden, a histological measure of Z-AAT accumulation, was reduced from a baseline mean of 5.9 to a post-baseline mean of 2.3 at the postbaseline liver biopsy visit.
Improvement in portal inflammation was observed in 42% of patients, while only 7% showed worsening.
Lastly, 50% of patients achieved an improvement in fibrosis of at least one point by METAVIR stage.
In contrast, by week 48, patients receiving a placebo who had baseline fibrosis (n=9) saw no meaningful changes from baseline in serum Z-AAT, a 26% increase in liver Z-AAT, and no meaningful change in PAS-D globule burden.
No placebo patients experienced an improvement in portal inflammation.
44% experienced worsening, 22% of placebo patients experienced worsening, while 38% experienced an improvement in fibrosis at the postbaseline liver biopsy visit.
Fazirsiran has been well tolerated, with treatment-emergent adverse events reported to date generally well balanced between fazirsiran and placebo groups.
Price Action: ARWR shares are down 22.60% at $28.95 on the last check Monday.