A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort
Publication Details
Journal of the Formosan Medical Association
June 2024
Author(s)
Ming-Jen Lee1, Hung-Chou Kuo2, Lin-Na Chou3, Marianne T Sweetser4, Jiaan-Der Wang5
Affiliations
1Department of Neurology and Medical Genetics, National Taiwan University Hospital, Taipei City, Taiwan; 2Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Alnylam Pharmaceuticals, Cambridge, MA, USA; 4Alnylam Pharmaceuticals, Cambridge, MA, USA; 5Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung City, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung City, Taiwan
Abstract
Background:
Acute hepatic porphyrias (AHP) are rare genetic disorders associated with acute neurovisceral attacks and chronic symptoms. This analysis was conducted to examine the long-term efficacy and safety of givosiran in Taiwanese participants in the ENVISION study (NCT03338816).
Methods:
Patients (age ≥12 years) with AHP and recurrent attacks were randomized to receive givosiran 2.5 mg/kg or placebo for 6 months during the double-blind period. Patients then switched from placebo to givosiran (placebo crossover group) or continued taking givosiran (continuous givosiran group) during a 30-month open-label extension period. The total study duration was 36 months. An analysis was conducted that included patients enrolled in Taiwan (N = 7).
Results:
During the double-blind period and open-label extension period, the median annualized attack rates were 0.0 and 0.0, respectively, in the continuous givosiran group (n = 5) and 15.1 and 4.6, respectively, in the placebo crossover group (n = 2; 70 % decrease). Median annualized days of hemin use in the double-blind period and open-label extension period were 0.0 and 0.0, respectively, in the continuous givosiran group, and 23.8 and 5.0, respectively, in the placebo crossover group (79 % decrease). EQ-5D VAS scores remained relatively stable in both groups, and PPEQ responses indicated improved functioning and satisfaction in both groups. Delta-aminolevulinic acid and porphobilinogen levels remained low with long-term givosiran treatment. Serious adverse events were reported by 3 patients (43 %).
Conclusions:
Long-term efficacy and safety results in the Taiwan cohort are consistent with those in the global cohort.
PMID
38044204
DOI
10.1016/j.jfma.2023.10.016
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