{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:12:32Z","timestamp":1773810752460,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Danicopan is a first\u2010in\u2010class orally administered complement factor D inhibitor, approved as an add\u2010on therapy to ravulizumab or eculizumab for the treatment of clinically significant extravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Population pharmacokinetics (PK) and pharmacodynamics (PK\u2013PD) modeling was used to characterize danicopan PK and to evaluate the relationship between steady\u2010state exposure and alternative pathway (AP) activity using data from healthy participants and patients with PNH treated with ravulizumab or eculizumab to support the danicopan dose regimens. Danicopan PK was described using a two\u2010compartment model with linear elimination, with absorption characterized by a zero\u2010order release followed by first\u2010order absorption. Body weight, sex, renal impairment, formulation, and food status were identified as significant covariates affecting danicopan PK. Food status affected the absorption of danicopan but had a minimal effect on relative bioavailability. An inhibitory E\n                    <jats:sub>max<\/jats:sub>\n                    model was used to describe the PK\u2013PD relationship between danicopan exposure and AP activity; the IC50 and IC90 for AP inhibition were estimated to be 12\u2009ng\/mL and 108\u2009ng\/mL, respectively. PK\u2013PD simulations support the approved danicopan dosing regimens of 150\u2009mg or 200\u2009mg three times daily (tid) and achieve the required exposure for 90% AP inhibition at trough. For both regimens, near\u2010complete inhibition of AP activity (&lt;\u200910%) was predicted regardless of food status. Overall, the effects of demographics, baseline, and food status variables were not considered clinically significant. These findings support the approved 150\u2009mg and 200\u2009mg tid dosing regimens for danicopan in patients with PNH.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70209","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:26:58Z","timestamp":1772990818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population\n                    <scp>PK<\/scp>\n                    \u2013\n                    <scp>PD<\/scp>\n                    Modeling of Danicopan Add\u2010On Therapy in Participants With Paroxysmal Nocturnal Hemoglobinuria Treated With Ravulizumab or Eculizumab"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1543-810X","authenticated-orcid":false,"given":"Jun","family":"Chen","sequence":"first","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8896-4433","authenticated-orcid":false,"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4857-7385","authenticated-orcid":false,"given":"Hanbin","family":"Li","sequence":"additional","affiliation":[{"name":"QuanTx Consulting, Mountain View  California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajendra","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.28"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90250-T"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-016-0013-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195909"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-876136"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-876805"},{"issue":"1","key":"e_1_2_10_8_1","first-page":"81","article-title":"Ravulizumab Demonstrates Long\u2010Term Efficacy, Safety and Favorable Patient Survival in Patients With Paroxysmal Nocturnal Hemoglobinuria","volume":"104","author":"Kulasekararaj A.","year":"2025","journal-title":"Annals of Hematology"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13137"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000975024.35238.f0"},{"issue":"12","key":"e_1_2_10_11_1","first-page":"3188","article-title":"Danicopan: An Oral Complement Factor D Inhibitor for Paroxysmal Nocturnal Hemoglobinuria","volume":"106","author":"Risitano A. M.","year":"2021","journal-title":"Hematology"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011388"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(23)00315-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026299"},{"key":"e_1_2_10_15_1","unstructured":"Pharmaceutical and Medical Devices Agency \u201cReport on the deliberation results: Voydeya tablets 50mg (danicopan) \u201d(2023) https:\/\/www.pmda.go.jp\/files\/000271107.pdf."},{"key":"e_1_2_10_16_1","unstructured":"European Medicines Agency \u201cVOYDEYA. Summary of product characteristics \u201d(2024) https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/voydeya\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_10_17_1","unstructured":"US Food and Drug Administration \u201cVOYDEYA prescribing information \u201d(2024) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/218037s000lbl.pdf."},{"key":"e_1_2_10_18_1","unstructured":"Health Canada \u201cVoydeya. Product monograph \u201d(2024) https:\/\/pdf.hres.ca\/dpd_pm\/00076411.PDF."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867326666191001130342"},{"key":"e_1_2_10_20_1","unstructured":"ICON \u201cNONMEM user's guides V7.5 \u201d(2025) https:\/\/nonmem.iconplc.com."},{"key":"e_1_2_10_21_1","unstructured":"ClinicalTrials.gov \u201cA study of the effects of food and age on danicopan \u201d(2023) https:\/\/www.clinicaltrials.gov\/study\/NCT04551599."}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:22:06Z","timestamp":1773807726000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/psp4.70209"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70209","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"assertion":[{"value":"2025-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70209"}}