Trofinetide

Trofinetide is indicated for the treatment of Rett syndrome in people two years of age and older.{{cite web | title=Drug Approval Package: Daybue | website=U.S. Food and Drug Administration (FDA) | date=6 April 2023 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217026Orig1s000TOC.cfm | access-date=20 November 2023 | archive-date=20 November 2023 | archive-url=https://web.archive.org/web/20231120063022/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217026Orig1s000TOC.cfm | url-status=dead }}

Rett syndrome is a rare, genetic neurological and developmental disorder that affects the way the brain develops. People with Rett syndrome experience a progressive loss of motor skills and language. Most babies with Rett syndrome seem to develop as expected for the first six months of life. These babies then lose skills they previously had attained at approximately six to 18 months of age — such as the ability to crawl, walk, communicate, or use their hands. The hallmark of Rett syndrome is near constant repetitive hand movements, such as rubbing or clapping. Rett syndrome leads to severe impairments affecting nearly every aspect of life, including the ability to speak, walk, eat, and breathe.

It was developed by Neuren Pharmaceuticals that acts as an analogue of the neuropeptide (1-3) IGF-1, which is a simple tripeptide with sequence Gly-Pro-Glu obtained by enzymatic cleavage of the growth factor IGF-1 within the brain. Trofinetide has anti-inflammatory properties and was originally developed as a potential treatment for stroke,{{cite journal | vauthors = Bickerdike MJ, Thomas GB, Batchelor DC, Sirimanne ES, Leong W, Lin H, Sieg F, Wen J, Brimble MA, Harris PW, Gluckman PD | title = NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke | journal = Journal of the Neurological Sciences | volume = 278 | issue = 1–2 | pages = 85–90 | date = March 2009 | pmid = 19157421 | doi = 10.1016/j.jns.2008.12.003 | s2cid = 7789415 }}{{cite journal | vauthors = Cartagena CM, Phillips KL, Williams GL, Konopko M, Tortella FC, Dave JR, Schmid KE | title = Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3 | journal = Neuromolecular Medicine | volume = 15 | issue = 3 | pages = 504–14 | date = September 2013 | pmid = 23765588 | doi = 10.1007/s12017-013-8236-z | s2cid = 12522580 | url = https://zenodo.org/record/1232878 | access-date = 10 December 2019 | archive-date = 15 April 2023 | archive-url = https://web.archive.org/web/20230415192353/https://zenodo.org/record/1232878 | url-status = live }} but has subsequently been developed for other applications and is approved by the FDA as an oral solution. It has successfully completed phase III clinical trial against Rett syndrome.{{cite web|url=https://www.rettsyndrome.org/wp-content/uploads/Neuren_PositivetoplineresultsfromPhase3trialinRettsyndrome.pdf|title=Positive top-line results from pivotal Phase 3 trial in Rett syndrome|date=7 December 2021|website=Rettsyndrome.org|access-date=21 July 2022|archive-date=18 August 2022|archive-url=https://web.archive.org/web/20220818204545/https://www.rettsyndrome.org/wp-content/uploads/Neuren_PositivetoplineresultsfromPhase3trialinRettsyndrome.pdf|url-status=live}} Trofinetide has also had a successful phase II trial against Fragile X syndrome.{{cite journal | vauthors = Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, Cogram P | title = NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome | journal = Neuromolecular Medicine | volume = 17 | issue = 1 | pages = 71–82 | date = March 2015 | pmid = 25613838 | doi = 10.1007/s12017-015-8341-2 | s2cid = 11964380 }}{{cite web|url=http://www.rettstudy.com/study-details/|title=Study Details - Rett Syndrome Study|website=Rettstudy.com|access-date=21 July 2022|archive-date=4 October 2016|archive-url=https://web.archive.org/web/20161004190344/http://www.rettstudy.com/study-details/|url-status=dead}}{{cite web|url=https://www.fraxa.org/neuren-trofinetide-successful-fragile-x-syndrome-clinical-trial/|title=Neuren's Tofinetide Successful in Phase 2 Clinical Trial in Fragile X|website=Fraxa.org|date=7 December 2015|access-date=21 July 2022|archive-date=24 June 2022|archive-url=https://web.archive.org/web/20220624232141/https://www.fraxa.org/neuren-trofinetide-successful-fragile-x-syndrome-clinical-trial/|url-status=live}} The drug is manufactured by Acadia Pharmaceuticals.{{cite press release | title=Acadia Pharmaceuticals Announces U.S. FDA Approval of Daybue (trofinetide) for the Treatment of Rett Syndrome in Adult and Pediatric Patients Two Years of Age and Older | website=Acadia Pharmaceuticals | date=11 March 2023 | url=https://acadia.com/en-us/media/news-releases/acadia-pharmaceuticals-announces-us-fda-approval-daybuetm | access-date=12 March 2025}}

The US Food and Drug Administration (FDA) evaluated the efficacy and safety of trofinetide based on a randomized, double-blind, placebo-controlled, 12-week study (Study 1; NCT04181723) of participants with Rett syndrome five to 20 years of age. Participants were randomized to receive trofinetide (N=93) or matching placebo (N=94) for 12 weeks. The dose of trofinetide was based on participant weight to achieve similar exposure in all participants. The FDA granted the application for trofinetide priority review, orphan drug, and fast track designations.

{{reflist}}

• {{ClinicalTrialsGov|NCT04181723|Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER)}}

{{Other nervous system drugs}}

{{Growth factor receptor modulators}}

{{Portal bar | Medicine}}

{{Authority control}}

Category:Anti-inflammatory agents

Category:Tripeptides

Category:Orphan drugs