{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:41:52Z","timestamp":1790343712073,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Upregulation of hepatic delta\u2010aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta\u2010aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims: evaluate long\u2010term efficacy and safety of givosiran in acute hepatic porphyria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (\u226512\u00a0years) with recurrent attacks received givosiran (2.5\u00a0mg\/kg monthly) (n\u00a0=\u00a048) or placebo (n\u00a0=\u00a046) for 6\u00a0months (double\u2010blind period); 93 received givosiran (2.5\u00a0mg or 1.25\u00a0mg\/kg monthly) in the open\u2010label extension (continuous givosiran, n\u00a0=\u00a047\/48; placebo crossover, n\u00a0=\u00a046\/46). Endpoints included annualized attack rate, urinary delta\u2010aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double\u2010blind period, 0.0 in open\u2010label 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\u2010blind period) and 0.0 (open\u2010label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long\u2010term givosiran led to sustained lowering of delta\u2010aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double\u2010blind period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Long\u2010term 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15090","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T16:20:53Z","timestamp":1635610853000},"page":"161-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Efficacy and safety of givosiran for acute hepatic porphyria: 24\u2010month interim analysis of the randomized phase 3 ENVISION study"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5026-6400","authenticated-orcid":false,"given":"Paolo","family":"Ventura","sequence":"first","affiliation":[{"name":"Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert L.","family":"Bonkovsky","sequence":"additional","affiliation":[{"name":"Section on Gastroenterology and Hepatology Wake Forest University\/North Carolina Baptist Medical Center  Winston\u2010Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gouya","sequence":"additional","affiliation":[{"name":"Centre Fran\u00e7ais des Porphyries  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Aguilera\u2010Peir\u00f3","sequence":"additional","affiliation":[{"name":"Hospital Clinic Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Montgomery Bissell","sequence":"additional","affiliation":[{"name":"UCSF Liver Center and Porphyria Center, University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope E.","family":"Stein","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Balwani","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Karl E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch  Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Parker","sequence":"additional","affiliation":[{"name":"University of Utah  Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kuter","sequence":"additional","affiliation":[{"name":"Center for Hematology Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Monroy","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeeyoung","family":"Oh","sequence":"additional","affiliation":[{"name":"Konkuk University Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Ritchie","sequence":"additional","affiliation":[{"name":"University of Alberta Hospital  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Ko","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Hua","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne T.","family":"Sweetser","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Sardh","sequence":"additional","affiliation":[{"name":"Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the ENVISION Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61925-5"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-423186"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2014.06.036"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30936"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1297"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29313"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-142-6-200503150-00010"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608634"},{"issue":"1","key":"e_1_2_15_10_1","first-page":"11","article-title":"Porphyria diagnostics\u2010part 1: a brief overview of the porphyrias","volume":"86","author":"Ramanujam VM","year":"2015","journal-title":"Curr Protoc Hum Genet"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S48605"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.03.002"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14459"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2014.891456"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.17925\/USN.2020.16.1.66"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9544-4"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12750"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-018-0319-3"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.97"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2012-200791"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1996.21847000.x"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_458"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-154-8-201104190-00015"},{"key":"e_1_2_15_24_1","unstructured":"Recordati Rare Disease Inc.US Prescribing Information: PANHEMATIN (hemin for injection).2017."},{"key":"e_1_2_15_25_1","unstructured":"Alnylam Pharmaceuticals Inc.GIVLAARI Highlights of Prescribing Information.2019.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/0212194s000lbl.pdf"},{"key":"e_1_2_15_26_1","unstructured":"Alnylam Pharmaceuticals Inc. 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