Phase III LAVENDER trial of Daybue in Rett syndrome published in Nature Medicine

In the study, treatment with Daybue (n=93) demonstrated statistically significant improvement compared to placebo (n=94) on both co-primary efficacy endpoints, with the following key findings:. The mean change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score was -5.1 and -1.7 in the Daybue and placebo groups, respectively. Based on the mixed-effects model for repeated measures (MMRM) analysis, the least squares mean (LSM) [SE] change from baseline to week 12 in the RSBQ total score was statistically significantly greater with Daybue (- 4.9 [0.94]) than with placebo (- 1.7 [0.90]), with an LSM placebo-subtracted difference of -3.1 [1.30], a 95% confidence interval (CI) of -5.7 to - 0.6, a p-value of 0.0175, and a Cohen’s d effect size of 0.37.

Change from baseline for all RSBQ domain subscores were numerically in favor of Daybue. At week 12 in the Daybue and placebo groups, respectively, the mean [SE] Clinical Global Impression–Improvement (CGI-I) scores were 3.5 [0.08] and 3.8 [0.06]. MMRM analysis showed a statistically significant improvement with Daybue compared with placebo at week 12, with a LSM [SE] difference of -0.3 [0.10], a 95% CI of - 0.5 to - 0.1, a p-value of 0.0030 and a Cohen’s d effect size of 0.47. A subgroup analysis showed a similar benefit with Daybue over placebo irrespective of age, baseline RSBQ severity, and category of documented disease-causing MECP2 mutation severity.

See: "Trofinetide for the treatment of Rett syndrome: a randomized phase iii study" Jeffrey L. Neul et al. Nature Medicine (2023) Published: 08 June 2023 https://www.nature.com/articles/s41591-023-02398-1