Genetic and Congenital

Trofinetide shows promise for Rett syndrome in Phase 3 study

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In a Phase 3 clinical trial, trofinetide, a synthetic analog of a specific protein, has shown promising results in treating the core symptoms of Rett syndrome, according to a study.

The study demonstrated significant improvements in behavior, global impression, and communication abilities in individuals with Rett syndrome who received trofinetide compared to those who received a placebo.

In the Phase 3 study, females with Rett syndrome were randomized to twice-daily oral trofinetide (n = 93) or placebo (n = 94) for a period of 12 weeks.

For the coprimary efficacy endpoints, the least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire showed a notable difference between the trofinetide and placebo groups, with values of -4.9 versus -1.7, respectively (P = 0.0175; Cohen’s d effect size, 0.37). In addition, the LSM Clinical Global Impression-Improvement at week 12 demonstrated another significant distinction with scores of 3.5 versus 3.8 (P = 0.0030; effect size, 0.47).

In terms of the key secondary efficacy endpoint, the LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist Social Composite score was also notably different between the groups, showing values of -0.1 for the trofinetide group versus -1.1 for the placebo group (P = 0.0064; effect size, 0.43).

Common treatment-emergent adverse events included diarrhea, reported in 80.6% of participants in the trofinetide group compared to 19.1% in the placebo group. However, it was largely described as mild to moderate in severity.

Neul JL, Percy AK, Benke TA, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023;29(6):1468-1475. doi: 10.1038/s41591-023-02398-1. Epub 2023 Jun 8. PMID: 37291210; PMCID: PMC10287558.