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 factorIGF-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]
^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.
PMID19157421.
S2CID7789415.
^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.
PMID25613838.
S2CID11964380.