Efficacy and safety of givosiran for acute hepatic porphyria: 24‐month interim analysis of the randomized phase 3 ENVISION study
| Autor: | D Karl E Anderson, Paula Aguilera-Peiró, Laurent Gouya, David J. Kuter, Charles J. Parker, Zhaowei Hua, Marianne T. Sweetser, Herbert L. Bonkovsky, Penelope E. Stein, Bruce Ritchie, Envision Investigators, Manisha Balwani, John J. Ko, Eliane Sardh, Paolo Ventura, Susana Monroy, D. Montgomery Bissell, Jeeyoung Oh |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Acetylgalactosamine Pyrrolidines givosiran Urinary system Acute Hepatic Porprhyria ALA-synthase-1 givosiran health-related quality of life RNAi therapeutics Attack rate Placebo chemistry.chemical_compound Quality of life Internal medicine Porphobilinogen Humans Medicine Adverse effect ALA-synthase-1 Hepatology business.industry Acute Hepatic Porprhyria RNAi therapeutics Interim analysis Porphyrias Hepatic health-related quality of life chemistry Porphyria Acute Intermittent Quality of Life business Hemin |
| Zdroj: | Liver International. 42:161-172 |
| ISSN: | 1478-3231 1478-3223 |
| DOI: | 10.1111/liv.15090 |
| Popis: | Background & aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life. |
| Databáze: | OpenAIRE |
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