Chemistry:Trofinetide

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Short description: Pharmaceutical drug
Trofinetide
Trofinetide.svg
Clinical data
Trade namesDaybue
Other namesNNZ-2566
AHFS/Drugs.comMonograph
MedlinePlusa623019
License data
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability84%
MetabolismInsignificant
Elimination half-life~ 1.5 h
ExcretionUrine
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC13H21N3O6
Molar mass315.326 g·mol−1
3D model (JSmol)

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

The most common adverse reactions include diarrhea and vomiting.[2]

Trofinetide was approved for medical use in the United States in March 2023.[1][2][3] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[4]

Medical uses

Trofinetide is indicated for the treatment of Rett syndrome in people two years of age and older.[1][5]

Rett syndrome is a rare, genetic neurological and developmental disorder that affects the way the brain develops.[2] People with Rett syndrome experience a progressive loss of motor skills and language.[2] Most babies with Rett syndrome seem to develop as expected for the first six months of life.[2] 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.[2] The hallmark of Rett syndrome is near constant repetitive hand movements, such as rubbing or clapping.[2] Rett syndrome leads to severe impairments affecting nearly every aspect of life, including the ability to speak, walk, eat, and breathe.[2]

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,[6][7] but has subsequently been developed for other applications and is now approved by the FDA as an oral solution. It has successfully completed Phase III clinical trial against Rett syndrome.[8] Trofinetide has also had a successful Phase II trial against Fragile X syndrome.[9][10][11] The drug is manufactured by Acadia Pharmaceuticals.[citation needed]

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.[2] Participants were randomized to receive trofinetide (N=93) or matching placebo (N=94) for 12 weeks.[2] The dose of trofinetide was based on participant weight to achieve similar exposure in all participants.[2]

The FDA granted the application for trofinetide priority review, orphan drug, and fast track designations.[2]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Daybue- trofinetide solution". 29 March 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67e6f2d9-21f6-466f-9def-826c6a4b8257. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 "FDA approves first treatment for Rett Syndrome". 13 March 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-rett-syndrome.  This article incorporates text from this source, which is in the public domain.
  3. ↑ "Trofinetide: First Approval". Drugs 83 (9): 819–824. June 2023. doi:10.1007/s40265-023-01883-8. PMID 37191913. https://figshare.com/articles/online_resource/Trofinetide_First_Approval/22705549. 
  4. ↑ (PDF) New Drug Therapy Approvals 2023 (Report). January 2024. https://www.fda.gov/media/175253/download. Retrieved 9 January 2024. 
  5. ↑ "Drug Approval Package: Daybue". 6 April 2023. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217026Orig1s000TOC.cfm. 
  6. ↑ "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. doi:10.1016/j.jns.2008.12.003. PMID 19157421. 
  7. ↑ "Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3". Neuromolecular Medicine 15 (3): 504–14. September 2013. doi:10.1007/s12017-013-8236-z. PMID 23765588. https://zenodo.org/record/1232878. Retrieved 2019-12-10. 
  8. ↑ "Positive top-line results from pivotal Phase 3 trial in Rett syndrome". 7 December 2021. https://www.rettsyndrome.org/wp-content/uploads/Neuren_PositivetoplineresultsfromPhase3trialinRettsyndrome.pdf. 
  9. ↑ "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. doi:10.1007/s12017-015-8341-2. PMID 25613838. 
  10. ↑ "Study Details - Rett Syndrome Study". http://www.rettstudy.com/study-details/. 
  11. ↑ "Neuren's Tofinetide Successful in Phase 2 Clinical Trial in Fragile X". 7 December 2015. https://www.fraxa.org/neuren-trofinetide-successful-fragile-x-syndrome-clinical-trial/. 

External links

  • Clinical trial number NCT04181723 for "Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER)" at ClinicalTrials.gov



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