Abstract Details

Title Trofinetide for the Treatment of Girls Aged Two to Four Years with Rett Syndrome: Final Results from the Open-label DAFFODIL Study

Topic Child Neurology and Developmental Neurology

Presentation(s) S37 - Emerging Therapies in Child Neurology (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective To investigate the safety/tolerability and exploratory efficacy of long-term treatment with trofinetide in girls aged 2–4 years with Rett syndrome (RTT).

Background RTT is a rare, debilitating, neurodevelopmental disorder that mostly affects females. Trofinetide treatment demonstrated significant improvements in core symptoms of RTT and an acceptable safety profile in studies of females aged ≥5 years. Here, we report the long-term safety and efficacy results of DAFFODIL (NCT04988867), which studied trofinetide in a younger patient population.

Design/Methods DAFFODIL was a multicenter, open-label, long-term phase 2/3 study of trofinetide in females aged 2–4 years with RTT. Twice-daily trofinetide was dosed by weight and administered orally or by gastrostomy tube. Safety and 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]) results are shown. Optional exit interviews of caregivers of trial participants were also conducted.

Results Fifteen participants were enrolled; 12 completed the trial. Diarrhea (80.0%) and vomiting (53.3%) were the most common TEAEs, all of mild/moderate severity. Serious TEAEs (n=4) were unrelated to treatment. No deaths were reported. Mean ± standard error CGI-I score was 3.5±0.18 at Week 2 and continued to improve to 2.2±0.22 at Week 78. The mean CaGI-I score (2.1±0.31) was “much improved” relative to Baseline at Week 78. ICND-QOL scores improved (3.9±0.24 to 4.6±0.31 from Baseline to Week 78). Seven caregivers participated in the exit interviews and most frequently reported improvements in new words (5/7), eye contact (4/7), and hand use (4/7). Weight-based dosing achieved the target exposure and was similar to that of participants aged 5–20 years in other trofinetide studies.

Conclusions Treatment with trofinetide was well tolerated in girls aged 2–4 years with RTT and resulted in long-term improvements in efficacy endpoints.

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.
Di Di An	No disclosure on file
Mona Darwish, PhD	Dr. Darwish has received personal compensation for serving as an employee of Acadia.
Dilesh Doshi, PharmD (Acadia)	Dr. Doshi has received personal compensation for serving as an employee of Acadia Pharmaceuticals.
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..
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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