{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:13:03Z","timestamp":1792818783957,"version":"4.5.0"},"reference-count":9,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Current treatments for Friedreich's ataxia, a neurodegenerative disorder characterized by decreased intramitochondrial frataxin, do not address low frataxin concentrations. Nomlabofusp (previously CTI\u20101601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin deficiency. Phase 1 studies assessed the safety, pharmacokinetic, and pharmacodynamic profiles of subcutaneously administered nomlabofusp in adults with Friedreich's ataxia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were enrolled in two Phase 1, double\u2010blind, placebo\u2010controlled studies. The single ascending\u2010dose (SAD) study (NCT04176991) evaluated single doses of nomlabofusp (25, 50, 75, or 100\u2009mg) or placebo. The multiple ascending\u2010dose (MAD) study (NCT04519567) evaluated nomlabofusp (25\u2009mg daily for 4\u2009days then every third day, 50\u2009mg daily for 7\u2009days then every 2\u2009days, or 100\u2009mg daily) or placebo for 13\u2009days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients aged 19\u201369\u2009years were enrolled (SAD, <jats:italic>N<\/jats:italic>\u2009=\u200928; MAD, <jats:italic>N<\/jats:italic>\u2009=\u200927). Nomlabofusp was generally well tolerated through 13\u2009days. Most adverse events were mild and resolved quickly. No serious adverse events or deaths were reported. Peak nomlabofusp plasma concentrations occurred 15\u2009min after subcutaneous administration. Nomlabofusp plasma exposures increased with increasing doses and daily administration and decreased with reduced dosing frequency. Increased frataxin concentrations were observed in buccal cells, skin, and platelets with higher and more frequent nomlabofusp administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Results from this study support a favorable safety profile for nomlabofusp. Subcutaneous nomlabofusp injections were quickly absorbed; higher doses and daily administration resulted in increased tissue frataxin concentrations. Future studies will evaluate longer\u2010term safety and possible efficacy of nomlabofusp.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51971","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T04:40:13Z","timestamp":1707108013000},"page":"540-553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Safety, pharmacokinetics, and pharmacodynamics of nomlabofusp (<scp>CTI<\/scp>\u20101601) in Friedreich's ataxia"],"prefix":"10.1002","volume":"11","author":[{"given":"Russell","family":"Clayton","sequence":"first","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Galas","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreen","family":"Scherer","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Farmer","sequence":"additional","affiliation":[{"name":"Friedreich's Ataxia Research Alliance (FARA)  Downingtown Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Hamdani","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Schecter","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bettoun","sequence":"additional","affiliation":[{"name":"Larimar Therapeutics, Inc.  Bala Cynwyd Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.736253"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.01.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610173351601"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448230"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2019.11.006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063958"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.07.001"},{"key":"e_1_2_8_9_1","volume-title":"Bioanalytical Method Validation Guidance for Industry","author":"Food and Drug Administration","year":"2018"},{"key":"e_1_2_8_10_1","volume-title":"Guideline on Bioanalytical Method Validation (EMEA\/CHMP\/EWP\/192217\/2009 Rev. 1 Corr. 2)","author":"European Agency for the Evaluation of Medicinal Products","year":"2011"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51971","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T03:14:56Z","timestamp":1711422896000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,4]]},"references-count":9,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/acn3.51971"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51971","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,4]]},"assertion":[{"value":"2023-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}