Results From This Study are Encouraging for Alpha-1 Antitrypsin Deficiency Liver Disease


Takeda and its collaborator, Arrowhead Pharmaceuticals, recently announced results from AROAAT-2002 of the investigational drug fazirsiran. The drug is an RNA interference therapeutic developed to lessen alpha-1 antitirypsin protein Z-AAT production.

Accumulation of inflammatory Z-AAT is possibly the cause of advanced liver disease in alpha-1 antitrypsin deficiency (AATD) patients. By reducing Z-AAT concentrations inflammation will be reduced and the liver will be allowed to regenerate and be repaired.

The results were published in the New England Journal of Medicine and featured in a presentation at the 2022 International Liver Congress.  Arrowhead conducted the trial.

Dr. Pavel Strnad, the principal investigator of the AROAAT-2002 study, referred to the study results saying that preexisting liver damage may now be meaningfully improved by treatment with fazirsiran.

He stated further that an even more exciting aspect of the trial is that by targeting a siRNA therapeutic into the liver there is a potential to treat previously untreatable liver disease.

About AAT and AATD

AAT is a protein made by the liver and released into the bloodstream. It helps to protect the lungs from disease and damage which can cause difficulty in breathing.

AATD occurs in approximately one out of every three to five thousand people in the U.S. It is an inherited disorder causing the lack of, or low levels of, alpha-1 antitrypsin in the blood.

Presently, there are no therapies for liver disease that occurs as a result of AATD.

About the Trial

The Phase 2 AROAAT Study (NCT03946449) is an open-label study investigating the efficacy and safety of the investigational drug fazirsiran. Sixteen patients with liver fibrosis and AATD-associated liver disease participated in the trial. The patients were separated into three cohorts (arms).

Eligible patients were subject to a pre-dose biopsy and another biopsy at the end of the study.

About the Study Results

z-AAT accumulation in the liver was reduced by a median of eighty-three percent. The accumulated mutant AAT protein was reduced in all sixteen patients as well as the globule (spherical) burden.

About Safety

Fazirsiran was well tolerated. There were no deaths, dose interruptions, or discontinuations over a period of one and one-half years. Four moderately serious events occurred but were resolved with the four patients continuing to receive fazirsiran.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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