PARIS — Givosiran, an investigational RNA interference therapeutic, was generally well-tolerated and reduced aminolevulinic acid and porphobilinogen accumulation in patients with acute hepatic porphyrias and ameliorate disease manifestations, according to a presentation at the International Liver Congress 2018.
“Acute intermittent porphyria is a rare disorder which is caused by mutations in heme synthesis,” Eliane Sardh, MD, PhD, from the Karolinska University Hospital in Sweden, told Healio Gastroenterology and Liver Disease. “I have presented new data on a new therapeutic treatment where we use interfering RNA to downgrade [aminolevulinic acid synthase 1 (ALAS1)] mRNA levels in these patient groups.”
Two patients experienced serious adverse events during the phase 1/2 study. One patient presented upper extremity deep vein thrombosis, which the researchers assessed as unlikely related to the drug due to the presence of indwelling central veinous catheter and a prior history of venous damage from chronic hemin use. The other patient had an anaphylactic reaction after the third dose of givosiran (Alnylam), which the researchers assessed as related to the drug.
The researchers observed a mean 60% to 70% maximal reduction in ALAS1 mRNA relative to baseline with concomitant reductions of aminolevulinic acid and porphobilinogen by over 80%
Additionally, patients showed an 83% mean decrease in annual attack rate compared with placebo and an 88% mean decrease in annual number of hemin doses required in treatment compared with a run-in period.
For more information:
Sardh E, et al. GS-016. Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.
Disclosure: Sardh reports no relevant financial disclosures.
Editor’s note: This item has been updated to reflect the most recent data presented.