{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:55:22Z","timestamp":1791456922684,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>\n                    Hereditary angioedema (HAE) with C1 inhibitor deficiency is a rare disorder characterized by unpredictable, potentially life\u2010threatening recurrent angioedema attacks. Lanadelumab is a fully human monoclonal antibody with selective binding to active plasma kallikrein, and prevents the formation of cleaved high molecular weight kininogen (cHMWK) and bradykinin, thereby preventing HAE attacks. The clinical pharmacology of lanadelumab was characterized following subcutaneous administration in 257 subjects (24 healthy subjects and 233 patients with HAE). The pharmacokinetics of lanadelumab were described using a one\u2010compartment model with first\u2010order rate of absorption and linear clearance, showing slow absorption and a long half\u2010life (14.8\u00a0days). A covariate analysis retained body weight and health status on apparent clearance (CL\/F) and body weight on volume of distribution (V\/F). Population estimates of CL\/F and V\/F were 0.0249\u00a0L\/hour (0.586\u00a0L\/day) and 12.8\u00a0L, respectively. An indirect\u2010response Imax model showed 53.7% maximum suppression in cHMWK formation with a low potential for interactions with concomitant medications (analgesic, anti\u2010inflammatory, and antirheumatic medications). A 300\u00a0mg dose administered Q2W was associated with a mean steady\u2010state minimum concentration (C\n                    <jats:sub>min,ss<\/jats:sub>\n                    ; 25.4\u00a0\u03bcg\/mL) that was ~\u00a04.5\u2010fold higher than the half\u2010maximal inhibitory concentration for cHMWK reduction (5.71\u00a0\u03bcg\/mL). Exposure\u2010response analyses suggest that 300\u00a0mg Q2W dosing was associated with a significantly reduced HAE attack rate, prolonged time to first attack after treatment initiation, and lower need for concomitant medications. The response was comparable across patient body weight groups. Findings from this analysis support the dosing rationale for lanadelumab to prevent attacks in patients with HAE.\n                  <\/jats:p>","DOI":"10.1111\/cts.12806","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T17:02:38Z","timestamp":1589475758000},"page":"1208-1216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacokinetics, Pharmacodynamics, and Exposure\u2010Response of Lanadelumab for Hereditary Angioedema"],"prefix":"10.1111","volume":"13","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Shire, a Takeda company Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Marier","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-2993","authenticated-orcid":false,"given":"Nastya","family":"Kassir","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Chang","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Martin","sequence":"additional","affiliation":[{"name":"Shire, a Takeda company Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13384"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14059"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-016-8561-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.569061"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605767"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.16773"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2014.05.028"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13601-017-0172-9"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011970125687"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_10_11_1","first-page":"261","volume-title":"Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications","author":"Gabrielsson J.","year":"2016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9534-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805538"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2012.02.020"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613627"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2015.01.003"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12379"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-012-0027-4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596370-000000000-00000"},{"key":"e_1_2_10_20_1","first-page":"84","article-title":"The pharmacokinetics and pharmacodynamics of monoclonal antibodies\u2013mechanistic modeling applied to drug development","volume":"10","author":"Mould D.R.","year":"2007","journal-title":"Curr. Opin. Drug Discov. Devel."},{"key":"e_1_2_10_21_1","volume-title":"A safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of lanadelumab to prevent hereditary angioedema (HAE) attacks in pediatric participants of 2 years to less than (<) 12 years of age (SPRING)","author":"ClinicalTrials.gov."},{"key":"e_1_2_10_22_1","volume-title":"Study to evaluate the real\u2010world effectiveness of lanadelumab in participants with hereditary angioedema (HAE) (EMPOWER)","author":"ClinicalTrials.gov."},{"key":"e_1_2_10_23_1","volume-title":"Study to evaluate the real\u2010world long\u2010term effectiveness of lanadelumab in participants with hereditary Angioedema (HAE) (ENABLE)"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcts.12806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12806","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:30:23Z","timestamp":1693805423000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,26]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/cts.12806"],"URL":"https:\/\/doi.org\/10.1111\/cts.12806","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,26]]},"assertion":[{"value":"2020-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}