Trofinetide for the Treatment of Girls Aged Two to Four Years with Rett Syndrome: Final Results from the Open-label DAFFODIL Study
Alan Percy1, Robin Ryther2, Eric Marsh3, Timothy Feyma4, David Lieberman5, Jeffrey Neul6, Timothy Benke7, Daniel Glaze8, Elizabeth Berry-Kravis9, Amitha Ananth10, Colleen Buhrfiend9, Di An11, Mona Darwish11, Dilesh Doshi11, Kathie Bishop11, James Youakim11
1University of Alabama at Birmingham, 2Washington University School of Medicine, 3Children's Hospital of Philadelphia, 4Gillette Children's Specialty Healthcare, 5Boston Children's Hospital, 6Vanderbilt University Medical Center, 7Children’s Hospital of Colorado/University of Colorado School of Medicine, 8Baylor College of Medicine, 9Rush University Medical Center, 10University of Alabama at Birmingham/Pediatric Neurology, 11Acadia Pharmaceuticals, Inc.
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.