VIENNA — An “exciting, novel RNAi therapy” significantly lowered acute hepatic porphyria recurrent attacks, according to data presented during the International Liver Congress 2019.
“Fifty percent of the givosiran patients were attack-free for the 6-month study duration compared to 16.3% of the placebo-treated patients. This is a highly clinical endpoint and these patients were severely affected at baseline,” Manisha Balwani, MD, MS, of the Icahn School of Medicine at Mount Sinai, said during a press conference.
Balwani and colleagues recruited patients with at least two porphyria attacks in the previous 6 months. They randomly assigned patients to receive subcutaneous givosiran (Alnylam) 2.5 mg/kg (n = 48) or placebo (n = 46) monthly for 6 months. The aim was to analyze the annual rate of porphyria attacks that required hospitalization, urgent care or intravenous hemin treatment. Secondarily, researchers looked at delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) urine levels, rate of hemin usage, rate of attacks and quality of life.
Balwani reported that after givosiran, patients had a 74% lower mean annualized rate of composite attacks compared with placebo (P = 6.04 x 10-9) while the median annualized rate of composite attacks decreased by 90% relative to placebo.
Treated patients saw reductions in urinary ALA and PBG and lower usage of hemin relative to placebo.
“These improvements were consistent and seen across all groups,” Balwani said. Patients also self-reported improved quality of life, she added.
“A greater proportion of patients on givosiran reported improvements in their overall health, daily functioning and treatment satisfaction, compared to placebo,” Balwani said in her formal presentation.
Though adverse events were reported in most patients (80.4% in the placebo group; 89.6% with givosiran) and serious adverse events were reported in 20.8% of givosiran patients, only one patient discontinued treatment due to transaminase elevation and 93 of the 94 patients enrolled in the open-label extension of this study. – by Katrina Altersitz
Balwani M. GS-14. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.
Disclosures: Balwani reports receiving financial compensation as an advisory board member for Alnylam. Alnylam sponsored the study. The Icahn School of Medicine at Mount Sinai holds issued and pending patents related to givosiran and has licensed these patents to Alnylam.
Editor's Note: This item has been updated to reflect an accurate P value and other numbers.