Ponni Subbiah, MD, MPH, Chief Medical Officer at Acadia Pharmaceuticals, discusses the results of the LAVENDER trial, which led to the approval of trofinetide (DAYBUE) in patients with Rett syndrome.
Rett Syndrom Background
Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls appear to develop normally during the first 6 to 18 months of life, followed by a developmental “plateau.” Eventually, there is rapid regression in language and motor skills as synaptic connections deteriorate over time. This complex disease is typically caused by a genetic mutation in the MECP2 gene.
Common symptoms include:
- hand-wringing
- fits of screaming and inconsolable crying
- autistic features
- panic-like attacks
- bruxism
- episodic apnea and/or hyperpnea
- gait ataxia and apraxia
- tremors
- seizures
- slowed head growth.
Most patients with Rett syndrome live into adulthood but require round-the-clock care.
The U.S. Food and Drug Administration (FDA) recently approved trofinetide to treat individuals with Rett syndrome, 2 years of age and older. Trofinetide is a synthetic peptide designed to target and modulate the activity of specific brain receptors thought to be involved in the pathophysiology of Rett syndrome.
The LAVENDER Trial
The approval of trofinetide was supported by the LAVENDER study, a phase 3, randomized, double-blind, placebo-controlled trial of trofinetide in patients 5 to 20 years of age with Rett syndrome. The co-primary endpoints of LAVENDER were changes from baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) total score at week 12, and Clinical Global Impression-Improvement (CGI-I) score at week 12. The RSBQ is a caregiver assessment that evaluates a range of symptoms of Rett syndrome including vocalizations, facial expressions, eye gaze, hand movements (or stereotypies), repetitive behaviors, breathing, night-time behaviors, and mood. The CGI-I is a global physician assessment of whether a patient has improved or worsened.
Results of the study demonstrated that treatment with trofinetide demonstrated statistically significant improvement, compared to placebo on both co-primary efficacy endpoints. On the RSBQ, the change from baseline to week 12 was -5.1 in the treatment arm vs. -1.7 in the placebo arm (P = .0175). The CGI-) score at week 12 was 3.5 in the treatment arm vs. 3.8 in the placebo arm (P = .0030).
The most common adverse events were diarrhea (82% in the treatment arm, 19% in placebo) and vomiting (29% in the treatment arm, 10% in placebo). The majority of these events were mild-to-moderate and did not lead to discontinuation.
Trofinetide is now available for prescription, as of April 17, 2023.
For more information about Rett syndrome, visit our Rett Syndrome Learning page here: https://checkrare.com/rett-syndrome/