A plain language summary of results from the LAVENDER study: trofinetide treatment for Rett syndrome

This is a summary of an article about the LAVENDER study, which was published in Nature Medicine in June 2023. The study involved girls and young women with a rare genetic condition called Rett syndrome, which affects the way the brain develops. Researchers wanted to find out if a drug called trofinetide could improve the symptoms of Rett syndrome. A total of 187 girls and young women took trofinetide (brand name DAYBUE™) liquid or a placebo (something that looks the same as the trofinetide liquid but does not contain medicine) 2 times a day either by drinking it or through a tube into the stomach called a gastrostomy tube (g-tube). Changes in Rett syndrome symptoms were looked for by study doctors for 12 weeks by using a rating scale called the Clinical Global Impression–Improvement (CGI–I) and by caregivers (usually a parent) who completed a questionnaire called the Rett Syndrome Behaviour Questionnaire (RSBQ). Caregivers were also asked to rate communication and social interaction skills, which resulted in the ‘Social Composite’ score on a questionnaire called the Communication and Symbolic Behavior Scales Developmental Profile™ Infant–Toddler (CSBS-DP-IT) checklist. After 12 weeks of treatment, girls and young women who received trofinetide had greater improvements in their symptoms than those who took the placebo, as rated by the RSBQ and CGI–I. Participants who took trofinetide could communicate better than participants who took the placebo as rated on the CSBS–DP–IT Social Composite scale. The differences between trofinetide and the placebo were statistically significant, which means that it was unlikely that the benefit seen with trofinetide was caused by chance. The most common side effects in the trofinetide group were diarrhea (frequent watery bowel movements) and vomiting, and in almost all cases these were mild or moderate. In the LAVENDER study, trofinetide helped girls and young women with Rett syndrome by improving several important symptoms. This is the first study to show that a medicine, trofinetide, improves the symptoms of Rett syndrome. Clinical Trial Registration: NCT04181723 (LAVENDER) ( ClinicalTrials.gov )