Trofinetide

Last updated

Trofinetide
Trofinetide.svg
Clinical data
Trade names Daybue
Other namesNNZ-2566
AHFS/Drugs.com Monograph
MedlinePlus a623019
License data
Routes of
administration 		By mouth
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability 84%
Metabolism Insignificant
Elimination half-life ~ 1.5 h
Excretion Urine
Identifiers
  • (2S)-2-{[(2S)-1-(2-aminoacetyl)-2-methylpyrrolidine-2-carbonyl]amino}pentanedioic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula C13H21N3O6
Molar mass 315.326 g·mol−1
3D model (JSmol)
  • C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(=O)O)C(=O)O
  • InChI=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
  • Key: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. [1]

Contents

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]

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References

  1. 1 2 3 4 5 "Daybue- trofinetide solution". DailyMed. 29 March 2023. Archived from the original on 2 July 2023. Retrieved 20 November 2023.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves first treatment for Rett Syndrome". U.S. Food and Drug Administration (FDA). 13 March 2023. Archived from the original on 13 March 2023. Retrieved 13 March 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. ↑ Keam SJ (June 2023). "Trofinetide: First Approval". Drugs. 83 (9): 819–824. doi:10.1007/s40265-023-01883-8. PMID   37191913. S2CID   258715933.
  4. ↑ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
  5. ↑ "Drug Approval Package: Daybue". U.S. Food and Drug Administration (FDA). 6 April 2023. Archived from the original on 20 November 2023. Retrieved 20 November 2023.
  6. ↑ Bickerdike MJ, Thomas GB, Batchelor DC, Sirimanne ES, Leong W, Lin H, et al. (March 2009). "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. doi:10.1016/j.jns.2008.12.003. PMID   19157421. S2CID   7789415.
  7. ↑ Cartagena CM, Phillips KL, Williams GL, Konopko M, Tortella FC, Dave JR, et al. (September 2013). "Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3". Neuromolecular Medicine. 15 (3): 504–14. doi:10.1007/s12017-013-8236-z. PMID   23765588. S2CID   12522580. Archived from the original on 15 April 2023. Retrieved 10 December 2019.
  8. ↑ "Positive top-line results from pivotal Phase 3 trial in Rett syndrome" (PDF). Rettsyndrome.org. 7 December 2021. Archived (PDF) from the original on 18 August 2022. Retrieved 21 July 2022.
  9. ↑ Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, et al. (March 2015). "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. doi:10.1007/s12017-015-8341-2. PMID   25613838. S2CID   11964380.
  10. ↑ "Study Details - Rett Syndrome Study". Rettstudy.com. Archived from the original on 4 October 2016. Retrieved 21 July 2022.
  11. ↑ "Neuren's Tofinetide Successful in Phase 2 Clinical Trial in Fragile X". Fraxa.org. 7 December 2015. Archived from the original on 24 June 2022. Retrieved 21 July 2022.
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