{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:45:08Z","timestamp":1789202708224,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adimanebart (ARGX\u2010119), a first\u2010in\u2010class, humanized, agonistic monoclonal antibody, specifically targets and activates muscle\u2010specific kinase, stabilizing the neuromuscular junction, increasing muscle strength, and decreasing muscle weakness and fatigability in nonclinical, proof\u2010of\u2010concept studies. Adimanebart may have broad therapeutic potential in neuromuscular junction disorders. This Phase I, first\u2010in\u2010human, double\u2010blinded, placebo\u2010controlled study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of adimanebart in healthy participants. With no pharmacodynamic marker for muscle\u2010specific kinase dimerization by adimanebart, human dose predictions were based on the minimum anticipated biological effect level in nonclinical studies. In this two\u2010part study, 112 healthy participants were randomized to receive adimanebart or placebo in single ascending intravenous doses (0.005\u201015 mg\/kg) or a single subcutaneous dose (5 mg\/kg; Part A; n = 76), or weekly multiple ascending intravenous doses (0.3\u20105 mg\/kg; Part B; n = 36). Adimanebart was well tolerated with a favorable safety profile. In single\u2010ascending dose (SAD) cohorts, adimanebart demonstrated nonlinear pharmacokinetics at low concentrations, a dose\u2010proportional increase in maximum concentration (mean range: 0.1\u2010343 \u00b5g\/mL), and a \u22486\u2010fold increase in area under the concentration\u2013time curve (0 to infinity) following a single intravenous dose, indicating target\u2010mediated drug disposition. Incidence and prevalence of adimanebart anti\u2010drug antibodies were comparable between treatment groups in SAD cohorts (adimanebart: 16.0% and 18.0%, placebo: 16.7% and 22.2%, respectively) and were not detected in multiple\u2010ascending\u2010dose cohorts. There was no apparent impact of anti\u2010drug antibodies on adimanebart pharmacokinetics or safety. This study supports investigation of adimanebart as an agonistic muscle\u2010specific kinase monoclonal antibody treatment for neuromuscular junction disorders.<\/jats:p>","DOI":"10.1002\/jcph.70208","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:42:27Z","timestamp":1779187347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["First\u2010in\u2010Human Dose Selection and Safety, Tolerability, Pharmacokinetics, and Immunogenicity of the Muscle\u2010Specific Kinase Agonist Adimanebart (ARGX\u2010119)"],"prefix":"10.1002","volume":"66","author":[{"given":"Tonke van","family":"Bragt","sequence":"first","affiliation":[{"name":"Curare Consulting B.V.  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