Background

• Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration in March 2023 for the treatment of Rett syndrome (RTT) in adults and pediatric patients aged ≥2 years1
• In the phase 3 LAVENDER™ study in females with RTT aged 5–20 years (NCT04181723), trofinetide provided statistically significant improvements over placebo in caregiver- and clinician-rated efficacy measures
and demonstrated an acceptable safety profile2
◦ Previous phase 2 studies have also demonstrated trofinetide to be efficacious and well tolerated in the treatment of RTT3,4
• Weight-based dosing of trofinetide was used in LAVENDER to achieve the target exposure (area under the concentration-time curve over the dosing interval [12 hours] at steady state [AUC0–12,ss] of 800–1200 µg•h/mL) that was previously identified in a phase 2 study4
• Initial exposure-response (E-R) modeling of the phase 2 studies in females with RTT using predicted exposure parameters and selected efficacy endpoints suggested a correlation between trofinetide AUC0–12,ss and
magnitude of response on the Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression–Improvement (CGI-I) scale, the coprimary endpoints in LAVENDER
◦ The E-R RSBQ model was used to identify the target exposure and guide weight-banded dose selection for LAVENDER

By; Darwish M, Julie Passarell, Kelly Maxwell, Youakim JM, Bradley H, and Bishop KM.

Encore poster presented at: 52nd Annual Child Neurology Society (CNS) Meeting; October 4-7, 2023; Vancouver, BC, Canada.