Trofinetide Explained

Tradename:Daybue
Dailymedid:Trofinetide
Routes Of Administration:By mouth, feeding tube (gastrostomy tube)
Atc Prefix:None
Legal Us:Rx-only
Bioavailability:84%
Metabolism:Insignificant
Elimination Half-Life:~ 1.5 h
Excretion:Urine
Cas Number:853400-76-7
Pubchem:11318905
Drugbank:DB06045
Chemspiderid:9493869
Unii:Z2ME8F52QL
Kegg:D12400
Chebi:229599
Chembl:197084
Synonyms:NNZ-2566
Iupac Name:(2S)-2-pentanedioic acid
C:13
H:21
N:3
O:6
Smiles:C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(=O)O)C(=O)O
Stdinchi:1S/C13H21N3O6/c1-13(5-2-6-16(13)9(17)7-14)12(22)15-8(11(20)21)3-4-10(18)19/h8H,2-7,14H2,1H3,(H,15,22)(H,18,19)(H,20,21)/t8-,13-/m0/s1
Stdinchikey:BUSXWGRAOZQTEY-SDBXPKJASA-N

Trofinetide, sold under the brand name Daybue, is a medication used for the treatment of Rett syndrome.[1] It is taken by mouth.

The most common adverse reactions include diarrhea and vomiting.

Trofinetide was approved for medical use in the United States in March 2023.[2] [3] [4] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[5]

Medical uses

Trofinetide is indicated for the treatment of Rett syndrome in people two years of age and older.[6]

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.

History

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,[7] [8] 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.[9] Trofinetide has also had a successful phase II trial against Fragile X syndrome.[10] [11] [12] The drug is manufactured by Acadia Pharmaceuticals.

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.

Notes and References

  1. Web site: Daybue- trofinetide solution . DailyMed . 29 March 2023 . 20 November 2023 . 2 July 2023 . https://web.archive.org/web/20230702061340/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67e6f2d9-21f6-466f-9def-826c6a4b8257 . live .
  2. Web site: FDA approves first treatment for Rett Syndrome . U.S. Food and Drug Administration (FDA) . 13 March 2023 . 13 March 2023 . 13 March 2023 . https://web.archive.org/web/20230313153136/http://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-rett-syndrome . live .
  3. Keam SJ . Trofinetide: First Approval . Drugs . 83 . 9 . 819–824 . June 2023 . 37191913 . 10.1007/s40265-023-01883-8 . 258715933 .
  4. Web site: Drug Trials Snapshots: Daybue . U.S. Food and Drug Administration (FDA) . 12 March 2023 . 19 July 2024.
  5. New Drug Therapy Approvals 2023 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 9 January 2024 . https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download . 10 January 2024 . live .
  6. Web site: Drug Approval Package: Daybue . U.S. Food and Drug Administration (FDA) . 6 April 2023 . 20 November 2023 . 20 November 2023 . https://web.archive.org/web/20231120063022/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217026Orig1s000TOC.cfm . live .
  7. Bickerdike MJ, Thomas GB, Batchelor DC, Sirimanne ES, Leong W, Lin H, Sieg F, Wen J, Brimble MA, Harris PW, Gluckman PD . NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke . Journal of the Neurological Sciences . 278 . 1–2 . 85–90 . March 2009 . 19157421 . 10.1016/j.jns.2008.12.003 . 7789415 .
  8. Cartagena CM, Phillips KL, Williams GL, Konopko M, Tortella FC, Dave JR, Schmid KE . Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3 . Neuromolecular Medicine . 15 . 3 . 504–14 . September 2013 . 23765588 . 10.1007/s12017-013-8236-z . 12522580 . 10 December 2019 . 15 April 2023 . https://web.archive.org/web/20230415192353/https://zenodo.org/record/1232878 . live .
  9. Web site: Positive top-line results from pivotal Phase 3 trial in Rett syndrome. 7 December 2021. Rettsyndrome.org. 21 July 2022. 18 August 2022. https://web.archive.org/web/20220818204545/https://www.rettsyndrome.org/wp-content/uploads/Neuren_PositivetoplineresultsfromPhase3trialinRettsyndrome.pdf. live.
  10. Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, Cogram P . NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome . Neuromolecular Medicine . 17 . 1 . 71–82 . March 2015 . 25613838 . 10.1007/s12017-015-8341-2 . 11964380 .
  11. Web site: Study Details - Rett Syndrome Study. Rettstudy.com. 21 July 2022. 4 October 2016. https://web.archive.org/web/20161004190344/http://www.rettstudy.com/study-details/. dead.
  12. Web site: Neuren's Tofinetide Successful in Phase 2 Clinical Trial in Fragile X. Fraxa.org. 7 December 2015. 21 July 2022. 24 June 2022. https://web.archive.org/web/20220624232141/https://www.fraxa.org/neuren-trofinetide-successful-fragile-x-syndrome-clinical-trial/. live.

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