Monthly Treatment Is Safe, Efficacious for Acute Hepatic Porphyria

Monthly givosiran treatments for patients with acute hepatic porphyria (AHP) led to sustained reductions in annualized attack rates and use of hemin, increased quality of life, and no long-term safety concerns, according to the results of a randomized phase 3 trial.

In the phase III ENVISION study, treatment with givosiran for 6 months was previously found to reduce attacks and other diseases compared with placebo.

The 36-month final analysis of the ENVISION study included 94 patients with AHP aged 12 years and older. All participants had recurrent attacks and were randomized 1:1 to receive givosiran (n = 48) or placebo (n = 46) for 6 months. Individuals in the medication group received subcutaneous givosiran 2.5 mg/kg. Additionally, individuals initially receiving placebo received either givosiran 2.5 mg/kg or 1.25 mg/kg for 6 months or longer before switching to 2.5 mg/kg in the open-label extension period.

The mean annualized attack rate (AAR) was 0.4 during givosiran treatment through month 36. The annualized days of hemin use remained low in the continuous treatment group (median 0.0 to 0.4) and decreased in the placebo crossover group (16.2 to 0.4).

>>Quiz: True or false: Many individuals with acute hepatic porphyria never experience symptoms.

The results indicated that by the end of the open-label extension period, 86% of the continuous treatment group and 92% of the placebo crossover group had no attacks. In the post hoc analysis, AAR was lower than the historical AAR in 98% and 100% of the groups, respectively. Additionally, there were 0 days of hemin use in 88% and 90% of the groups, respectively.

The patient-reported quality of life outcomes, as reported by the 12-item short-form health survey, showed an increase of 8.6 and 9.4 for the physical component summary scores of the groups, respectively. Similarly, there was an increase of 8.1 and 3.2 for the mental component summary scores. The EQ-5d health-related questionnaire scores increased by 18.9 in the continuous treatment group and 9.9 in the placebo crossover group. Both lower urinary delta-amniolevulinic acid and porphobilinogen levels were sustained.

While the authors note this is the largest interventional study for AHP to date, a limitation of the study includes the relatively small sample size.

“In conclusion, the final results from the phase III ENVISION study confirm that long-term monthly dosing with givosiran is well tolerated and provides sustained and continuous benefit to patient with AHP.”

Reference:

Kuter DJ, Bonkovsky HL, Monroy S, et al; ENVISION Investigators. Efficacy and safety of givosiran for acute hepatic porphyria: final results of the randomized phase III ENVISION trial. J Hepatol. 2023;79(5):1150-1158. doi: 10.1016/j.jhep.2023.06.013