Photo Credit: SvetaZi
The following is a summary of “Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA),” published in the October 2024 issue of Gastroenterology by Clark et al.
Homozygous ZZ alpha-1 antitrypsin (AAT) deficiency leads to the production of mutant AAT proteins, causing progressive liver fibrosis.
Researchers conducted a prospective study to assess the effects of fazirsiran on patients with .
They randomized 40 patients to receive subcutaneous placebo or fazirsiran at doses of 25, 100, or 200 mg. The primary endpoint was the percent change in serum Z-AAT concentration from baseline to week 16. Patients with fibrosis on baseline liver biopsy received treatment on day 1, week 4, and then every 12 weeks, followed by a second liver biopsy. Patients without fibrosis received 2 doses on day 1 and week 4.
The results showed that at week 16, least-squares mean percent declines in serum Z-AAT concentration were −61%, −83%, and −94% with fazirsiran 25, 100, and 200 mg, respectively, compared to placebo (all P< .0001). Efficacy was sustained through week 52. Fazirsiran reduced median liver Z-AAT concentration by 93% at postdose liver biopsy, while placebo increased by 26%. All patients treated with fazirsiran exhibited histologic reduction in hepatic globule burden.
The study concluded that fazirsiran significantly reduced both serum and liver concentrations of Z-AAT in a dose-dependent manner and effectively reduced hepatic globule burden.
Source: gastrojournal.org/article/S0016-5085(24)05181-3/fulltext
