Acute Intermittent Porphyria (AIP) is a metabolic disorder characterized by the deficiency of the enzyme hydroxymethylbilane synthase (HMBS). AIP results in the accumulation of toxic porphyrin precursors in the body, leading to weak muscles and pain. ALAS1 synthesis is a common complication of AI, which leads to neurovisceral attacks and disease manifestations. Givosiran is an RNA interference therapeutic agent that inhibits ALAS1 synthesis. This study aims to evaluate the efficacy of givosiran in AIP patients.

This is a phase-1 trial that included a total of 40 patients with AIP who underwent randomization. The patients divided into three groups; patients in group A (with recent porphyria attacks)received five ascending doses of givosiran or placebo, those in group B (without recent attacks) received once-monthly injections of one of two doses of givosiran or placebo, and those in group C (recurrent attacks) received 2.5 or 5.0 mg doses of givosiran or placebo. The primary outcomes were safety and efficacy. 

Common adverse events were nasopharyngitis, abdominal pain, and diarrhea. Treatment-related serious adverse events reported in 6 patients in the three groups combined. All the patients in group C who were assigned to givosiran had sustained reductions in ALAS1 messenger RNA, resulting in a 79% lower mean annualized attack rate.

The research concluded that monthly injections of givosiran in patients with AIP resulted in low-grade adverse events and lower rates of ALAS1 mRNA levels and porphyria attacks. 

Ref: https://www.nejm.org/doi/full/10.1056/NEJMoa1807838