Background & Aims: Acute hepatic porphyria (AHP) is caused by defects in hepatic
heme biosynthesis, leading to disabling acute neurovisceral attacks and chronic
symptoms. In ENVISION (NCT03338816), givosiran treatment for 6 months reduced
attacks and other disease manifestations, compared with placebo. Here we report data
from the 36-month final analysis of ENVISION.
Methods: Ninety-four patients with AHP (age ≥12 years) and recurrent attacks were
randomized 1:1 to monthly double-blind subcutaneous givosiran 2.5 mg/kg (N=48) or
placebo (N=46) for 6 months. In the open-label extension (OLE) period, 93 patients
received givosiran 2.5 or 1.25 mg/kg for 6 months or more before transitioning to 2.5
mg/kg. Endpoints were exploratory unless otherwise noted.
Results: During givosiran treatment, median annualized attack rate (AAR) was 0.4.
Through Month 36, annualized days of hemin use remained low in the continuous
givosiran group (median, 0.0 to 0.4) and decreased in the placebo crossover group
(16.2 to 0.4). At end of OLE, in the continuous givosiran and placebo crossover groups,
86% and 92%, respectively, had 0 attacks. AAR was lower than historical AAR in 98%
and 100%, respectively (post hoc analysis), and there were 0 days of hemin use in 88%
and 90%, respectively. The 12-item Short Form Health Survey physical and mental
component scores increased by 8.6 and 8.1, respectively (continuous givosiran) and 9.4
and 3.2, respectively (placebo crossover). EQ-5D health-related questionnaire scores
increased by 18.9 (continuous givosiran) and 9.9 (placebo crossover). Lowering of
urinary delta-aminolevulinic acid and porphobilinogen levels was sustained. Safety
findings demonstrated a continued positive risk/benefit profile for givosiran
