{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:52:03Z","timestamp":1770108723558,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":8,"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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary angioedema (HAE) is characterized by recurrent attacks of severe tissue swelling. In the OASIS\u2010HAE phase 3 study (NCT05139810), donidalorsen, an RNA\u2010targeted antisense oligonucleotide that reduces prekallikrein production in the liver, significantly reduced HAE attack rates. To characterize the relationship between prekallikrein concentrations and HAE attack rates following donidalorsen and predict the efficacy of potential dosing regimens, an exposure\u2013response model was developed using data from OASIS\u2010HAE. Simulations were conducted to evaluate the following regimens: 80\u2009mg once every 4\u2009weeks (Q4W), 8\u2009weeks (Q8W), 1\u2009month (Q1M), and 2\u2009months (Q2M), and a switch to Q2M dosing for patients who were attack\u2010free for 3\u2009months on the Q1M regimen. The relationship between prekallikrein concentrations and HAE attack rates was well characterized by a sigmoidal E\n                    <jats:sub>max<\/jats:sub>\n                    (maximum effect) model with baseline attack rate and baseline prekallikrein concentration included as covariates. The average prekallikrein concentration estimated to result in a 90% reduction in attack rate (EC\n                    <jats:sub>10<\/jats:sub>\n                    ) was 47.1\u2009mg\/L. Predicted percent reductions in attack rates at steady state were similar for Q4W (84.1%) vs. Q1M (82.9%) and Q8W (72.6%) vs. Q2M (70.2%) dosing. Predicted reductions in attack rate remained similar and clinically meaningful in patients who switched from Q1M to Q2M dosing (94.0% in month 1 and 91.3% in month 2 of the 2\u2010month dosing interval at steady state). Overall, exposure\u2013response analyses supported the efficacy of Q1M and Q2M dosing and indicated that switching to Q2M dosing could be a viable approach for patients who are attack\u2010free on the Q1M regimen.\n                  <\/jats:p>","DOI":"10.1111\/cts.70388","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:17:43Z","timestamp":1762755463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exposure\u2013Response Analysis of Donidalorsen for the Treatment of Hereditary Angioedema"],"prefix":"10.1111","volume":"18","author":[{"given":"Pratap","family":"Singh","sequence":"first","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Witjes","sequence":"additional","affiliation":[{"name":"Certara  Radnor Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huub Jan","family":"Kleijn","sequence":"additional","affiliation":[{"name":"Certara  Radnor Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-4680","authenticated-orcid":false,"given":"John K.","family":"Diep","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bordone","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth B.","family":"Newman","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7081-0573","authenticated-orcid":false,"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Ionis  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny M.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2023.100792"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223-021-00537-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.12.039"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.02.018"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613627"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.17121"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.10.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223\u2010023\u201000795\u20102"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2022.43.220046"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.12.025"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010022\u201002401\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.5152\/balkanmedj.2021.21094"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.11.011"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109329"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2018.0754"},{"key":"e_1_2_9_17_1","unstructured":"Dawnzera\u201cFull Prescribing Information Ionis Pharmaceuticals Inc \u201d(2025)."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2402478"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15948"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/Cpt.3607"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2023.04.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15214"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.03.032"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1274397"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2500\/AAP.2021.42.210017"},{"key":"e_1_2_9_26_1","unstructured":"CSL Behring \u201cHaegarda. 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