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Efruxifermin is an Fc\u2010FGF21 fusion protein with prolonged half\u2010life and enhanced receptor affinity compared with native human FGF21. Efruxifermin is in clinical trials for the treatment of non\u2010alcoholic steatohepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Efruxifermin was administered weekly to male and female Sprague Dawley rats for 4 or 26\u2009weeks. Body and organ weights, macroscopic and microscopic pathology, clinical chemistry, blood cytology and serum and urine biomarkers were analysed to characterize the pharmacodynamics of efruxifermin and to investigate potential non\u2010clinical toxicities following chronic administration of supra\u2010pharmacological doses of efruxifermin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Efruxifermin significantly reduced body weight gain after 4 and 26\u2009weeks, despite increasing food intake. Changes in tissue pathology, clinical chemistry and serum biomarkers generally appeared to be associated with weight loss, except for a significant decrease in urine volume in both males and females without perturbed electrolyte balance. Markers of sympathetic activation, urinary corticosterone and ratio of adrenal\u2010to\u2010body weight were unchanged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Efruxifermin attenuated body weight gain, consistent with other FGF21 analogues. In contrast to at least one other FGF21 analogue, efruxifermin decreased rather than increased urine volume. The absence of an increase in sympathetic tone in rats mirrors the unchanged salivary cortisol and systemic blood pressure following efruxifermin treatment in humans.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15725","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T05:19:48Z","timestamp":1636780788000},"page":"1384-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Efruxifermin, a long\u2010acting Fc\u2010fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-0297","authenticated-orcid":false,"given":"Erik J.","family":"Tillman","sequence":"first","affiliation":[{"name":"Akero Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Brock","sequence":"additional","affiliation":[{"name":"Brock Scientific Consulting, LLC  Montgomery Village Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-6903","authenticated-orcid":false,"given":"Tim","family":"Rolph","sequence":"additional","affiliation":[{"name":"Akero Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15541"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.05.002"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2012073117"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0221"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(00)00365-6"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00356.2007"},{"key":"e_1_2_12_8_1","first-page":"546A","article-title":"A phase 1 study of BMS\u2010986036 (pegylated FGF21) in healthy obese subjects","volume":"64","author":"Charles E. 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