Addressing the Core Features of Rett Syndrome With Trofinetide


The study author, a pediatric neurologist at Baylor College of Medicine and director of the Blue Bird Circle Rett Center at Texas Children’s Hospital, spoke about the investigational Rett syndrome treatment’s potential going forward.

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

Results of a recent phase 2 evaluation of an investigational treatment for Rett syndrome, trofinetide, show that it may be capable of providing a clinical benefit at a dose of 200 mg/kg twice daily.1

The trial assessed 5 syndrome-specific efficacy measurements, and the analog derived from a growth factor IGF-1 molecule showed significant differences from placebo in 3 of them. Meaningful improvements were seen in 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)

To find out more information about the Neuren and Acadia Pharmaceuticals product, NeurologyLive® spoke with study author Daniel Glaze, MD, a pediatric neurologist at Baylor College of Medicine and director of the Blue Bird Circle Rett Center at Texas Children’s Hospital.

NeurologyLive®: What prompted this work with trofinetide?

Daniel Glaze, MD: For individuals with Rett syndrome there is no cure and no Rett syndrome specific medication or treatment strategy. Treatment currently is based on symptom directed therapies—general, not Rett specific. For example, for epilepsy, we have a variety of antiepileptic drugs but not a Rett anti-seizure medication. Individuals with Rett syndrome experience numerous clinical problems including communication, behavioral, motor, gastrointestinal-nutrition and seizure related. The burden to the individual and to their family is great as the disorder is life long, impairment is severe and there is an increased risk of sudden unexpected death. There is a need for safe and efficacious treatment for this devastating disorder.

Is trofinetide attempting to target an unmet need?

Trofinetide appears to be a very promising drug for the treatment of the core features of Rett syndrome and to address this unmet need. It is an analog of insulin-like growth factor-1 (IGF1) with similar properties to reduce neuroinflammation and support synaptic function, both critical to normal brain development and response to injury, therefore very likely to improve brain functioning in Rett syndrome. Additionally, because it can be given orally and has a good safety profile without side effects such as hypoglycemia trofinetide has further advantages as a therapy for Rett syndrome.

What’s the main takeaway for the clinician community from this work?

Trofinetide demonstrates safety and efficacy for core symptoms of Rett syndrome in children with Rett syndrome, and along with a previous study demonstrating similar findings in adults with this disorder support a further phase 3 (“definitive study”).

Were any of the findings surprising or unexpected in any way?

In view of our previous study in adults with Rett syndrome, it was not too surprising that safety and efficacy would be demonstrated in children with this disorder. Somewhat surprising, in a very good way, was that efficacy was demonstrated for three different instruments which in different ways looked at core features of Rett syndrome and which were complete by different sets of observers, clinicians, and caretakers during a double-blinded placebo-controlled study. For me, this strengthened the possibility that trofinetide has the potential to be an effective and safe treatment for Rett syndrome.


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 28, 2019.

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