Authors :
Arthur Beisang, MD – Gillette Children's Specialty Healthcare
Loan Robinson, BS – Acadia Pharmaceuticals, Inc.
Presenting Author: Alyssa Peckham, PharmD – Acadia Pharmaceuticals, Inc.
Louise Cosand, PhD – Acadia Pharmaceuticals, Inc.
Ryan Bucco, PharmD – Acadia Pharmaceuticals, Inc.
Rationale:
Rett syndrome (RTT) is a rare neurodevelopmental disease primarily associated with loss-of-function mutations in the transcriptional regulator methyl-CpG binding protein-2 (MECP2) gene. RTT presents predominantly in female individuals, yet recent developments in genetic testing have added support to clinical observations that RTT can occur in males. Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the United States and patients aged ≥2 years weighing ≥9 kg in Canada, regardless of sex. Here, we present the real-world benefits and tolerability of trofinetide in male patients with RTT enrolled in LOTUS.
Methods:
LOTUS is an ongoing, phase 4 study of trofinetide use in the real world. Caregivers of patients who were prescribed trofinetide under routine clinical care were eligible to participate. This analysis focused on the male participants of the 18-month follow-up of the study. Assessments included the Behavioral Improvement Questionnaire (BIQ), the Gastrointestinal Health Questionnaire, and safety monitoring. Data are reported to 12 months since the initiation of trofinetide. Results:
In total, 7 caregivers of male patients with RTT participated in LOTUS, with a median (range) age of 8 (2-33) years. The median trofinetide dose at week 1 was 38.9% of the target dose and increased to over 89.2% by week 12. There was wide variability in dosing from months 4-12, reflecting individualized care. The behavioral improvements repeatedly reported by caregivers on the BIQ from months 1-12 included alertness, mood, purposeful use of hands, repetitive movements, grinding teeth, nonverbal communication, and social interaction/connectedness. Most caregivers reported formed/normal stools throughout the follow-up; most reports of diarrhea were contained inside the patients’ diaper. Adverse events were reported for 3 (42.9%) patients and consisted of pneumonia, sapovirus, and weight loss (n=1 for each, 33.3%)Conclusions:
The results of the 7 males with RTT included in this follow-up suggest that the real-world benefits and tolerability of trofinetide in males follow similar trends with the general population of LOTUS.Funding:
This study was funded by Acadia Pharmaceuticals Inc.