Treatment Provides Relief for Recurrent Acute Hepatic Porphyria Attacks

In patients with recurrent attacks of acute hepatic porphyria, treatment with givosiran led to a sustainable decrease in attacks and, subsequently, less chronic pain and health care dependency and improved quality of life. Researchers described acute hepatic porphyria, its burden, and the impact of givosiran in a review published in the Journal of Internal Medicine.

Acute hepatic porphyria encompasses several inherited metabolic disorders that affect hepatic heme biosynthesis and are associated with life-threatening neurovisceral manifestations, also known as acute porphyria attacks, the article explained.

“Although attacks are often sporadic, some patients develop recurrent acute attacks, with devastating effects on quality of life,” wrote Eliane Sardh, PhD, MD, and Pauline Harper, MD, PhD, of Karolinska University Hospital, Stockholm, Sweden, in the paper. “Liver transplantation has historically been the sole curative treatment option.”

Attacks are caused by accumulation of the heme precursor 5-aminolevulinic acid (ALA) and porphobilinogen. Clinical trials of givosiran, which seeks to normalize levels of ALAS1 through RNA interference, started in 2015. Phases 1, 2, and 3 were all randomized and placebo controlled.

“The results of clinical trials have shown that givosiran treatment leads to a rapid and sustained reduction of ALAS1 mRNA, decreased heme precursor levels, and a decreased rate of acute attacks compared with placebo,” the authors wrote.

Givosiran is currently approved for the treatment of acute hepatic porphyria in the United States and several other countries. In places where givosiran is not yet available, many patients from clinical trials have continued treatment through open-label extensions and compassionate-use programs.

“The successful development of givosiran from a scientific hypothesis to a medically approved drug in a relatively short time has been possible through committed collaboration between investigators, research nurses, patient organizations, patients, and a dedicated team at Alnylam Pharmaceuticals Inc,” the authors wrote.

Reference:
Sardh E, Harper P. RNAi therapy with givosiran significantly reduces attack rates in acute intermittent porphyria. J Int Med. Published online January 23, 2022. doi:10.1111/joim.13443