ARC-AAT / Arrowhead - LARVOL DELTA

Development of an RNAi therapeutic for alpha-1-antitrypsin liver disease. (PubMed, JCI Insight) - "The magnitude of AAT reduction and duration of response from first generation intravenously-administered RNA interference (RNAi) therapeutic ARC-AAT and then with next generation subcutaneously-administered ARO-AAT were assessed by measuring AAT protein in serum of the PiZ transgenic mouse model and human volunteers. RNAi therapy holds promise for the treatment of patients with AATD-associated liver disease. ARO-AAT is currently in Phase 2/3 clinical trials."

Journal

Hepatic-targeted RNA interference provides persistent knockdown of alpha-1 antitrypsin levels in ZZ patients. (PubMed, J Hepatol) - P1; "PiZZ and HV responded similarly to ARC-AAT. Deep and durable knockdown of hepatic AAT production based on observed reduction in serum AAT concentrations was demonstrated."

Clinical • Journal

Reduction of hepatic Z-alpha1 antitrypsin by RNA interference prevents and reverses liver disease including hepatic mitochondrial injury in the PiZ mouse model (EASL-ILC 2019) - "Sustained RNAi treatment not only prevented accumulation of disease-causing Z-AAT polymer but also reduced pre-existing polymer, inflammation, expression of fibrosis-associated genes and damage to hepatic mitochondria. RNAi holds great promise for the treatment of patients with AATD-associated liver disease."

Preclinical