• Paolo Ventura, Herbert L Bonkovsky, Laurent Gouya, Paula Aguilera-Peiró, Montgomery BissellDDUCSF Liver Center and Porphyria Center, University of California, San Francisco, CA, USA., 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, and ENVISION Investigators.
• Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit, University of Modena and Reggio Emilia, Modena, Italy.
• Liver Int. 2021 Oct 30.

Background & AimsUpregulation 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.Aimsevaluate long-term efficacy and safety of givosiran in acute hepatic porphyria.MethodsInterim 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.ResultsPatients 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.ConclusionsLong-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.© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.

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