Abstract Details

Title Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age

Topic Child Neurology and Developmental Neurology

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-005

Objective

To assess the safety/tolerability, preliminary efficacy, and pharmacokinetics (PK) of trofinetide in girls aged 2–4 years with Rett syndrome (RTT).

Background RTT is a rare, debilitating, neurodevelopmental disorder mainly affecting females. Trofinetide, a synthetic analog of a naturally occurring tripeptide in the brain, significantly improved core symptoms of RTT with an acceptable safety profile in studies enrolling females aged ≥5 years with RTT. However, RTT is typically diagnosed by 3 years of age.

Design/Methods This ongoing, multicenter, open-label study of trofinetide consists of a 12-week treatment period A and ~21-month treatment period B in females aged 2–4 years with RTT (NCT04988867). Weight-based dosing of trofinetide was administered orally or by gastrostomy tube twice-daily. Interim results (cut-off date March 14, 2022) from treatment period A are presented for safety, exploratory efficacy (Clinical Global Impression–Improvement [CGI-I], Caregiver Global Impression–Improvement [CaGI-I], and the Overall Quality-of-Life Rating on the Impact of Childhood Neurologic Disability Scale [ICND-QoL]), and PK.

Results At this interim analysis, 14 participants were enrolled, and 10 completed treatment period A. Twelve (85.7%) participants reported ≥1 treatment-emergent adverse event (TEAE). Diarrhea (64.3%) and vomiting (35.7%) were the most common TEAEs; no serious AEs or deaths were reported. Mean CGI-I scores improved from 3.6 at Week 2 to 3.3 at Week 12. The mean CaGI-I score at Week 12 (2.2) corresponded to “much improved” relative to Baseline. The ICND-QoL also improved, with an increase from 3.9 at Baseline to 4.2 at Week 12. Population PK analysis showed that exposure to trofinetide in this study achieved the target exposure range.

Conclusions Consistent with data from phase 2 and 3 trials with participants aged ≥5 years, treatment with trofinetide was well tolerated and appeared to result in improvements in RTT-related efficacy measures in girls aged 2–4 years.

Authors/Disclosures
Alan K. Percy, MD, FAAN PRESENTER	Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taysha Gene Therapies. Dr. Percy has received personal compensation in the range of $0-$499 for serving as a Consultant for Neurogene. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Taysha Gene Therapies. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for IOS Press.
Robin Ryther, MD, PhD	The institution of Dr. Ryther has received research support from Acadia.
Eric D. Marsh, MD, PhD (Children's Hospital of Philadlephia)	Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmacuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from NIH. The institution of Dr. Marsh has received research support from Rett Syndrome Research Trust. The institution of Dr. Marsh has received research support from International Rett Syndrome Foundation. The institution of Dr. Marsh has received research support from Eagles Autism Challenge. The institution of Dr. Marsh has received research support from LouLou Foundation. The institution of Dr. Marsh has received research support from International CDKL5 Resarch Foundation. The institution of Dr. Marsh has received research support from Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from Marinus. The institution of Dr. Marsh has received research support from Stoke Therapeutics. The institution of Dr. Marsh has received research support from Takeda Pharmaceuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Grant Review with NIH. Dr. Marsh has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Witness with Department of Human Services. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Medscape.
Timothy J. Feyma, MD (Gillette Children'S Specialty Healthcare)	Dr. Feyma has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Feyma has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for PTC Therapeutics.
David N. Lieberman, MD, PhD (Boston Children'S Hospital)	Dr. Lieberman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Lieberman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taysha Gene Therapies. Dr. Lieberman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene.
Jeffrey Neul, MD, PhD (Vanderbilt University Medical Center)	Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharmaceuticals. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Analysis Group. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taysha Gene Therapies. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alcyone. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ovid. Dr. Neul has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Neul has stock in LizardBio. The institution of Dr. Neul has received research support from NIH. The institution of Dr. Neul has received research support from Acadia. The institution of Dr. Neul has received research support from GW Pharmaceuticals. The institution of Dr. Neul has received research support from International Rett Syndrome Foundation. The institution of Dr. Neul has received research support from Rett Syndrome Research Trust.
Timothy A. Benke, MD, PhD	The institution of Dr. Benke has received research support from NIH, RSRT, IRSF and Children's Hospital Colorado. The institution of Dr. Benke has received research support from Acadia, GW, RSRT, Ovid/Takeda, Marinus. The institution of Dr. Benke has received research support from Acadia, CUREGRI, GRINtherapeutics, GW, IRSF, Marinus, Neurogene, Taysha, Ultragenyx and Zogenix/UCB; .
Daniel Glaze, MD (Baylor College of Medicine)	Dr. Glaze has nothing to disclose.
Elizabeth M. Berry-Kravis, MD, PhD (Rush University Medical Center)	The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Zevra. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren.
Amitha Ananth, MD (University of Alabama at Birmingham/Pediatric Neurology)	Dr. Ananth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reata Therapeutics. The institution of Dr. Ananth has received research support from Acadia Pharmaceuticals.
Colleen M. Buhrfiend, MD (Rush Univeristy Medical Center)	Dr. Buhrfiend has nothing to disclose.
	No disclosure on file
Kathie M. Bishop, PhD	Dr. Bishop has received personal compensation for serving as an employee of Acadia Pharmaceuticals, Inc. . Dr. Bishop has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for DTx Pharma. Dr. Bishop has stock in Acadia Pharmaceuticals, Inc..
Mona Darwish, PhD	Dr. Darwish has nothing to disclose.
James M. Youakim, MD (Acadia Pharmaceuticals)	Dr. Youakim has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Dr. Youakim has stock in Acadia Pharmaceuticals.

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