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 AAT deficiency liver disease.
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
The post Efficacy of Fazirsiran in AAT Deficiency Liver Disease first appeared on Physician's Weekly.