Fazirsiran is associated with a notable reduction in the concentration of Z-AAT, the most common form of alpha-1 antitrypsin (AAT) causing AAT deficiency (AATD), in the serum and liver as well as with improvements in the concentrations of liver enzymes, according to the results of a phase 2 clinical trial published in the New England Journal of Medicine.

The results of the trial, called AROAAT-2002, also showed that fazirsiran treatment led to the regression of fibrosis in some patients.

“The results from the AROAAT-2002 study provide multiple lines of evidence that preexisting liver damage in these patients may be meaningfully improved following treatment with fazirsiran,” Pavel Strnad, MD, the principal investigator of the trial, said in a press release.

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“Specifically, the improvements in histological globule burden, reduction in histological signs of portal inflammation, normalization of elevated liver enzymes, and improvement in liver fibrosis are all encouraging indicators that fazirsiran may rapidly ameliorate liver injury.”

The aim of AROAAT-2002 was to investigate the safety and efficacy of subcutaneous fazirsiran in patients with AATD-associated liver disease. The trial recruited 16 adult patients with the PiZZ phenotype who received either 200 or 100 mg of fazirsiran for a minimum of 3 doses or 200 mg of fazirsiran for a minimum of 5 doses.

Read more about the genetics of AATD

The primary outcome measure was the change from baseline in the concentrations of total, soluble, and insoluble Z-AAT in the liver.

The results showed that the accumulation of Z-AAT in the liver was reduced in all participants. Fazirsiran treatment was also associated with a reduction in histologic globule burden, which went from a mean score of 7.4 at baseline to 2.3 at week 24 or 48. Finally, the liver enzyme concentrations of all patients were reduced. The regression of fibrosis was seen in more than half (58%) of patients who received 200 mg of fazirsiran. 

The researchers reported no adverse events leading to trial or drug discontinuation. However, there were 4 serious adverse events, including viral myocarditis, diverticulitis, dyspnea, and vestibular neuronitis, which were later resolved.

Fazirsiran is an investigational RNA interference therapy designed to reduce the production of Z-AAT.


Results from phase 2 study of fazirsiran in patients with alpha-1 antitrypsin deficiency published in New England Journal of Medicine. News release. Takeda; June 27, 2022.

Study of ARO-AAT in patients with alpha-1 antitrypsin deficiency associated liver disease (AATD). ClinicalTrials.gov. May 10, 2019. Updated May 4, 2022. Accessed June 30, 2022.