{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:47:14Z","timestamp":1790858834883,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Sevasemten (EDG\u20105506) is an orally administered, investigational small molecule that selectively modulates fast muscle fiber contraction by inhibiting fast myosin ATPase. This study assessed the safety, tolerability, and pharmacokinetics (PK)\/pharmacodynamics (PD) of sevasemten in healthy adult volunteers (HVs) and adults with Becker muscular dystrophy (BMD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This randomized, double\u2010blind, placebo\u2010controlled phase 1 study was conducted at a single site. Eligible participants were 18\u201355\u2009years of age with a body mass index &lt;\u200930\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; adults with BMD were required to have a confirmed diagnosis based on documentation of pathogenic variant(s) in the dystrophin gene and a BMD phenotype. Participants were randomized 3:1 to receive sevasemten or placebo for up to 14\u2009days. Endpoints included adverse events (AEs), sevasemten PK and muscle concentration, and changes in biomarkers of muscle injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study enrolled 97 HVs in 7 single\u2010dose cohorts (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200957) and 5 multiple\u2010dose cohorts (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200940). Seven adults with BMD were enrolled in a multiple\u2010dose cohort. There were no serious AEs or AEs leading to trial discontinuation; the most common AEs were dizziness and somnolence. For adults with BMD, serum biomarkers of muscle injury trended down progressively with sevasemten treatment (average maximal reductions of 70% for creatine kinase, 98% for fast skeletal muscle troponin I, and 45% for myoglobin). Plasma proteomic analysis identified a signature of 125 elevated proteins characteristic of BMD that was reversibly lowered with sevasemten treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Sevasemten was generally well tolerated. Preliminary observations of decreases in biomarkers of muscle damage in adults with BMD support further clinical development.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      NCT04585464\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.28444","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:23:05Z","timestamp":1748841785000},"page":"399-407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Phase 1, Double\u2010Blind, Placebo\u2010Controlled Trial of Sevasemten (\n                    <scp>EDG<\/scp>\n                    \u20105506), a Selective Modulator of Fast Skeletal Muscle Contraction, in Healthy Volunteers and Adults With Becker Muscular Dystrophy"],"prefix":"10.1002","volume":"72","author":[{"given":"Joanne","family":"Donovan","sequence":"first","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Barthel","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"DuVall","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Madden","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"MacDougall","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Rempel","family":"Kilburn","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby","family":"Bronson","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Evanchik","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Gordon","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Koch","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-5008","authenticated-orcid":false,"given":"Alan J","family":"Russell","sequence":"additional","affiliation":[{"name":"Edgewise Therapeutics, Inc.  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