دورية أكاديمية
Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study
| العنوان: | Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study |
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| المؤلفون: | Paolo Ventura, Herbert L. Bonkovsky, Laurent Gouya, Paula Aguilera-Peiró, D. Montgomery Bissell, Penelope E. Stein, Manisha Balwani, D. Karl E. Anderson, Charles Parker, David J. Kuter, Susana Monroy, Jeeyoung Oh, Bruce Ritchie, John J. Ko, Zhaowei Hua, Marianne T. Sweetser, Eliane Sardh |
| المساهمون: | Ventura, Paolo, Bonkovsky, Herbert L., Gouya, Laurent, Aguilera-Peiró, Paula, Montgomery Bissell, D., Stein, Penelope E., Balwani, Manisha, Anderson, D. Karl E., Parker, Charle, Kuter, David J., Monroy, Susana, Oh, Jeeyoung, Ritchie, Bruce, Ko, John J., Hua, Zhaowei, Sweetser, Marianne T., Sardh, Eliane |
| سنة النشر: | 2021 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| مصطلحات موضوعية: | Acute Hepatic Porprhyria, ALA-synthase-1, givosiran, health-related quality of life, RNAi therapeutics |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34717041; info:eu-repo/semantics/altIdentifier/wos/WOS:000718809000001; volume:42; firstpage:161; lastpage:172; journal:LIVER INTERNATIONAL; http://hdl.handle.net/11380/1255839Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85119075466 |
| DOI: | 10.1111/liv.15090 |
| الإتاحة: | https://doi.org/10.1111/liv.15090Test http://hdl.handle.net/11380/1255839Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7F2B878E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/liv.15090 |
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