Fazirsiran Cuts Liver Z-AAT in AATD Patients
Pooled phase 2 data presented at The Liver Meeting 2026 show the siRNA therapy reduced disease-linked protein levels in alpha-1 antitrypsin deficiency liver disease.
Updated on Nov. 6, 2026 in Diseases — General
Pooled analyses of phase 2 trials found that fazirsiran 200 mg reduced intrahepatic Z-AAT by a median 89.6% compared with a 25.5% increase on placebo in patients with alpha-1 antitrypsin deficiency liver disease. The data were presented at The Liver Meeting 2026 in Denver, Colorado.
Why it matters
No pharmacologic therapy is currently approved for AATD liver disease, so a therapy that lowers the disease-causing protein addresses an unmet need. The findings build on earlier SEQUOIA results showing reduced serum and liver Z-AAT and lower hepatic globule burden.
The pooled phase 2 analysis of 56 patients (median age 56) showed a median 89.6% intrahepatic Z-AAT reduction with fazirsiran 200 mg versus a 25.5% increase with placebo. Whether these biomarker changes translate into clinical benefit over time remains unconfirmed pending phase 3 results.
The players
Pavel Strnad
Researcher at RWTH Aachen University Hospital who presented the pooled fazirsiran analysis, with work focused on liver disease and alpha-1 antitrypsin deficiency.
The details
Fazirsiran also reduced alanine aminotransferase by a median 35.6% and gamma-glutamyl transferase by 33.3% versus increases with placebo, and the METAVIR fibrosis score fell by a median 1.0 point. In the open-label extension, 34 patients (90%) reported treatment-emergent adverse events, mostly mild or moderate and unrelated to the study drug.
Timeline
November 5-9, 2026: Pooled fazirsiran data presented at The Liver Meeting 2026 in Denver, Colorado.
Health Landscape
The pooled results extend the SEQUOIA phase 2 trial, which first showed that fazirsiran reduced serum and liver Z-AAT and lowered hepatic globule burden in AATD liver disease. With no approved pharmacologic therapy for AATD-LD, these data add to a small but growing evidence base for RNA-targeted treatment of this inherited condition.
For people living with AATD liver disease, the therapy is still investigational and not yet available outside clinical trials. Current care remains focused on monitoring liver health, since no approved drug treats the underlying condition.
The takeaway
Lowering the disease-causing protein at its source is a promising direction for AATD liver disease, but patients and clinicians should await phase 3 outcomes before expecting an approved treatment. Routine liver monitoring and discussions with a hepatologist remain the practical steps today.
What happens next
A phase 3 trial evaluating fazirsiran 200 mg in AATD-LD is ongoing, and its results will determine whether the biomarker reductions translate into clinical benefit.
Further reading
Explore more on Diseases — General for context on inherited liver conditions and emerging treatments.
Source note: This article includes information reported by Hcplive.
