Authors :
Erin Prange, MSN, CRNP – Children's Hospital of Philadelphia
Shannon Standridge, DO, MPH – University of Cincinnati School of Medicine
Constance Smith-Hicks, MD, PhD – Center for Synaptic Disorders, Rett and Related Disorders Clinic, Kennedy Krieger Institute
Jennifer Tu, MD, PhD – University of California San Francisco Benioff Children's Hospital
Davut Pehlivan, MD – Baylor College of Medicine
Steven Skinner, MD – Greenwood Genetic Center
Cary Fu, MD – Vanderbilt Kennedy Center, Vanderbilt University Medical Center
Stephanie Kyle, PhD – Acadia Pharmaceuticals Inc.
Presenting Author: Alyssa Peckham, PharmD, BCPP – Acadia Pharmaceuticals Inc.
Rationale:
Trofinetide was approved by the US Food and Drug Administration in March 2023 for treating Rett syndrome in patients aged ≥2 years. Diarrhea was the most common adverse event and the leading cause of treatment discontinuation in clinical trials. Here, we present real-world experience with trofinetide titration and impact on tolerability.Methods:
In May 2024, a prescriber experience survey was sent to prescribers at US Rett syndrome centers of excellence (COEs) to collect real-world experience with trofinetide tolerability since approval.Results:
Overall, 67% (22/33) of prescribers from 89% (16/18) of COEs participated, accounting for 4.6% of trofinetide prescribers and 38.1% of trofinetide prescriptions nationwide since approval. In total, 86% (n=19) of respondents indicated that titrating trofinetide improves tolerability in treatment-naïve patients. Tolerability improvements included decreased diarrhea severity (77%, n=17), decreased trofinetide discontinuations (73%, n=16), improved caregiver quality of life (64%, n=14), and improved patient quality of life (59%, n=13). Respondents indicated that approximately 20% of patients may still discontinue trofinetide due to tolerability issues; however, discontinuation due to lack of efficacy was estimated to be much lower at approximately 5-8%.Conclusions:
Prescribers believe trofinetide titration helps with overall tolerability, specifically to decrease diarrhea severity and treatment discontinuations while improving patient and caregiver quality of life. Tolerability issues may persist in some patients which can lead to discontinuation. Prescribers believe discontinuation due to lack of efficacy remains low.
Funding: Acadia Pharmaceuticals Inc.