Trofinetide Triumphs in Phase 2 Study of Rett Syndrome


Of the 5 syndrome-specific efficacy measurements, trofinetide showed statistical benefits for patients with Rett syndrome on the Rett Syndrome Behavior Questionnaire, Clinical Global Impression Scale-Improvement, and the RTT Clinician Domain Specific Concerns-Visual Analog Scale.

Dr Daniel Glaze

Daniel Glaze, MD, a pediatric neurologist at the Baylor College of Medicine, and the director at the Blue Bird Circle Rett Center at Texas Childrens Hospital

Daniel Glaze, MD

Phase 2 study results have displayed that the 200-mg/kg dose of trofinetide provided a clinically meaningful and statistically significant benefit for pediatric patients with Rett syndrome for a trio of syndrome-specific efficacy measurements.1

Of the 5 measurements recorded in the trial, the Neuren product showed a benefit on both a pair of clinician assessments and a caregiver evaluation. All told, significant results were observed on the Rett Syndrome Behavior Questionnaire (RSBQ; P = .042), the Clinical Global Impression Scale-Improvement (CGI-I; P = .029), and the Rett Syndrome Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC; P = .025).

Additionally, study results also showed trofinetide was generally safe and well-tolerated at all dose levels (50 mg/kg, 100 mg/kg, and 200 mg/kg, all twice daily).

“Disease burden is severe for Rett patients and their families, and the impact of the disorder is life-long,” Daniel Glaze, MD, one of the study authors and a pediatric neurologist at the Baylor College of Medicine, and the director at the Blue Bird Circle Rett Center at Texas Children’s Hospital, said in a statement. “The data reported in this study show that females treated with trofinetide experienced lessened neurobehavioral impairments including social communication deficits, anxiety-like behavior, and mood dysregulation. These are very promising data for the Rett community that is currently without any FDA-approved treatment option.”

Altogether, the trial included 82 female patients aged 5 to 15 years. Steve Kaminsky, PhD, the Chief Science Officer of, noted in a statement that study results are very encouraging and provide strong evidence for its potential as a treatment for this disease, “a condition that leads to severe neurological impairments and is not only debilitating for the person with the disease, but also very hard on the families and caregivers of the children, mostly females, who are often unable to speak, walk, eat, and even breathe normally.”

Previously known as NNZ-2566, the agent is an analog of a molecule which is derived from the growth factor IGF-1 and occurs naturally in the brain. IGF-1 is a critical player in brain development and the response to injury and disease. According to Neuren, trofinetide is a chemically modified form of glypromate (GPE) that can mimic GPE’s natural function in the brain, thus resulting in an increased half-life for the drug while in the circulation, as well as “better stability for easier storage and shipping, and suitability for use as an oral medication, whereas GPE itself and IGF-1 can only be administered by injection.”2

Last year, Acadia Pharmaceuticals entered into an exclusive North American license agreement with Neuren for the development and commercialization of trofinetide for Rett syndrome, among other possible indications.

“Neuren has successfully led the clinical development of trofinetide to date, which allows us to further evaluate trofinetide as a potentially important treatment option for Rett syndrome,” said Serge Stankovic, MD, MSPH, ACADIA’s President. “In addition to achieving successful outcomes from early-stage clinical research with trofinetide for Rett syndrome, Neuren has fostered strong and enduring relationships with the Rett community. We will build on these efforts as we continue to study trofinetide for this unmet medical need.”

Acadia is planning to launch a phase 3 double-blind, randomized, placebo-controlled study evaluating trofinetide over the course of 12 weeks. It is expected to be initiated in the second half of 2019, after the completion of manufacturing scale-up activities. The phase 3 trial will seek to evaluate the therapy in 180 female patients aged 5 to 20 years, randomizing them in a 1:1 fashion. It will use the RSBQ and the CGI-I syndrome specific efficacy measures as co-primary efficacy endpoints.

Additionally, a 9-month, open-label extension study in which all participants, including those on placebo in the phase 3 study, will be eligible to receive trofinetide following the completion of said phase 3 trial. The extension study will follow all participants to explore long-term tolerability and safety of trofinetide.


1. Positive Phase 2 Study Results of Trofinetide in Pediatric Rett Syndrome Published in Neurology, the Medical Journal of the American Academy of Neurology [press release]. San Diego, CA; Cincinnati, OH; Melbourne, Australia: ACADIA Pharmaceuticals Inc.; Neuren Pharmaceuticals Limited;; Published March 27, 2018. Accessed March 27, 2019.

2. Product development: the science behind Neuren's products. Neuren website. Updated 2019. Accessed March 27, 2019.

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