Trofinetide Phase 2 Study Shows Safety and Clinically Relevant Improvement for Rett's Syndrome

Positive results from a phase 2 randomized, placebo-controlled clinical trial (NCT02715115) of trofinetide (Acadia Pharmaceuticals, San Diego, CA; Neuren Pharmaceuticals, Melbourne, Australia; and Rettsyndrome.org, Cincinnati, OH) for treatment of Rett syndrome have been published in Neurology. Girls age 5 to 15 years with Rett syndrome were enrolled (n = 82). After pretreatment baseline assessment, participants were randomly assigned to receive placebo or 1 of 3 doses of trofinetide (50 mg/kg, 100 mg/kg, and 200 mg/kg) twice daily. Trofinetide is a synthetic analog of insulin-like growth factor-1 (IGF-1) with Food and Drug Administration (FDA) fast track and orphan drug designations.

Participants given the highest dose had statistically significant improvements on 3 of 5 efficacy measures as shown in the Table. Changes in caregivers’ top 3 concerns and the Motor-Behavioral Assessment (MBA) were not statistically significant. Treatment with trofinetide at all doses was generally safe and well tolerated by participants with mostly mild or moderate adverse events, the most common across all groups were diarrhea, vomiting, upper respiratory tract infection, and fever; no serious adverse events were considered related to study medication. 

A 12-week phase 3 study evaluating the safety and efficacy of trofinetide and placebo is planned for the second half of 2019 and expects to enroll 180 girls and women, age 5 to 20 years, with Rett syndrome. The phase 3 study will be followed by a 9-month open-label extension study during which all participants will be eligible to receive trofinetide. 

 “Disease burden is severe for (patients with Rett) and their families, and the impact of the disorder is life-long,” said Daniel Glaze, MD, study author, Baylor College of Medicine, Department of Pediatrics and Neurology and Director at the Blue Bird Circle Rett Center, Texas Children’s Hospital. “The data reported in this study show that girls 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 US FDA-approved treatment option.”