{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:45:13Z","timestamp":1787589913737,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Mavacamten is a cardiac myosin inhibitor for adults with obstructive hypertrophic cardiomyopathy (HCM). Dose optimization is performed 4\u2009weeks after starting mavacamten, guided by periodic echo measurements of Valsalva left ventricular outflow tract gradient (VLVOTg) and left ventricular ejection fraction (LVEF). Previously, a population pharmacokinetic (PPK) model was developed and exposure\u2010response (E\u2010R) of VLVOTg (efficacy) and LVEF (safety) was used to identify the mavacamten titration regimen with the optimal benefit\/risk ratio, now included in the US prescribing information. Mavacamten is metabolized primarily by cytochrome P450 2C19 (CYP2C19) (74%), a highly polymorphic enzyme. China has a higher prevalence of poor CYP2C19 metabolizer phenotype compared with the global population; therefore, a previous model was adapted to include Chinese patients with obstructive HCM to identify the optimal dosing regimen for this population. Data from a phase I (healthy Chinese volunteers) and a phase III (EXPLORER\u2010CN, NCT05174416; Chinese patients with obstructive HCM) trial of mavacamten were added to the previous PPK and E\u2010R models, and the observed VLVOTg and LVEF from EXPLORER\u2010CN were successfully simulated. Next, five echocardiography\u2010guided titration regimens (plus the EXPLORER\u2010CN regimen) using representative or equal CYP2C19 phenotypes were simulated. The final simulated regimen recommended with an optimal benefit\/risk profile across CYP2C19 phenotypes included: down\u2010titration at Week 4 (if VLVOTg &lt;\u200920\u2009mmHg), restart at Week 12, and up\u2010titration at Week 12 (for VLVOTg \u2265\u200930\u2009mmHg and LVEF \u2265\u200955%), and every 12\u2009weeks thereafter. This supports the previously recommended regimen for Chinese patients with obstructive HCM, now approved by the National Medicinal Products Administration.<\/jats:p>","DOI":"10.1002\/psp4.13312","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T08:20:01Z","timestamp":1738052401000},"page":"751-758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010Informed Recommendation of Mavacamten Posology for Chinese Adults With Obstructive Hypertrophic Cardiomyopathy"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiaojie","family":"Wu","sequence":"first","affiliation":[{"name":"Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Puli","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanye","family":"Chen","sequence":"additional","affiliation":[{"name":"Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Tian","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiwen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Shanghai LianBio Development Co  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lyu","sequence":"additional","affiliation":[{"name":"Shanghai LianBio Development Co  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-3687","authenticated-orcid":false,"given":"Samira","family":"Merali","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2022.06.017"},{"key":"e_1_2_12_3_1","first-page":"e558","article-title":"2020 AHA\/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy","volume":"142","author":"Ommen S. 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