Data from a survey recently presented at the American Epilepsy Society (AES) 2024 Annual Meeting in Los Angeles, California, stated of 22 individuals who prescribed trofinetide (Daybue; Acadia Pharmaceuticals) for Rett syndrome, 86% indicated that titrating improved tolerability among treatment-naive patients.¹

Background

Trofinetide was the first drug approved by the FDA (March 13, 2023) for the treatment of Rett syndrome. It received Orphan Drug, Priority Review, and Fast Track Drug Designations, and is indicated for use in patients aged 2 years and older.²

Presented via a poster at AES, the authors noted that diarrhea was the most common adverse event and the leading cause of treatment discontinuation in clinical trials of trofinetide. In the real world, stated the authors, titration strategies are being used to improve tolerability.¹

The authors sought to explore this real-world experience using an electronic prescriber experience survey designed to collect real-world dosing strategies and their impact on tolerability.¹

Study data and results

"The survey was sent in May 2024 to 33 prescribers at 18 US Rett syndrome centers of excellence (COEs) designated by the International Rett Syndrome Foundation," wrote the investigators, led by Erin Prange, MSN, CRNP, a nurse practitioner in the Division of Neurology at Children's Hospital of Philadelphia.^1,3

The survey featured 22 prescribers from 16 COEs. According to the poster, the prescribers targeted for survey completion accounted for 38.1% of trofinetide prescriptions in the United States since it was approved.¹

Results stated that 86% (n = 19) of survey participants reported that titrating trofinetide improved tolerability in treatment-naïve patients.¹

"Specific tolerability improvements observed by respondents 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)," wrote the investigators.¹

The survey question read, "As compared with your experience when starting trofinetide at labeled dose (ie, clinical trial setting or real-world setting), has titration\ helped improve overall tolerability of trofinetide? If no or not sure, please explain how in comment field below."¹

Of the 22 participants, 1 replied "no," 1 replied "not sure," and another replied "other." These participants provided the following statements as a further explanation as to why they chose their respective answers, according to the poster presentation¹:

No - "Some patients do not like the taste; another vomits even with 5 mL dose."

Not sure - "I think there are patients that it doesn’t matter for, patients it is critical for, and patients that don’t tolerate no matter what we do."

Other - "Did not participate in the trofinetide clinical trials and/or I have never started patients at the full weight-banded dose."

Participants noted that approximately 20% of patients could still discontinue trofinetide treatment because of tolerability issues, though discontinuation because of lack of efficacy was estimated to be 5%-8%.¹

In a previous interview with Contemporary Pediatrics, Alan Percy, MD, Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at the University of Alabama, Birmingham, noted general pediatricians can have a role in prescribing trofinetide.⁴

"It's very interesting, and I can't give you an exact percentage, but maybe as high as 50% or so of the children that we have seen have had the medication prescribed by their private physician," Percy noted. "So the private physicians are being informed by the parents that this medication is available, and they are reaching out to the pharmacists to gain approval."⁴

"I think that general physicians should be quite confident in being able to prescribe this," he explained and noted for physicians unfamiliar with the treatment, COEs can offer guidance and support, helping to bridge the knowledge gap.⁴

Click here to watch the full interview with Percy, or click play on the video clip below.⁴

Conclusion

As for the survey data presented at AES, the investigators concluded, "Prescribers believe trofinetide titration helps with overall tolerability, specifically to decrease diarrhea severity and treatment discontinuations while improving patient and caregiver quality of life."¹

The pediatrician's role in prescribing trofinetide for Rett syndrome

References:

1. Prange E, Standridge SM, Smith-Hicks C, et al. Real-World Use of Trofinetide: A Survey of Tolerability From US Rett Syndrome Centers of Excellence. Poster presentation. Presented at: American Epilepsy Society (AES) 2024 Annual Meeting. December 6-10, 2024. Los Angeles, California.

2. Krewson, C. FDA approves trofinetide for treatment of Rett syndrome. Contemporary Pediatrics. March 13, 2023. Accessed December 9, 2024. https://www.contemporarypediatrics.com/view/fda-approves-trofinetide-for-treatment-of-rett-syndrome

3. Erin O'Connor Prange, MSN, CRNP. Children's Hospital of Philadelphia. Accessed December 9, 2024. https://www.chop.edu/nurse-practitioners/oconnor-prange-erin

4. Fitch, J. The pediatrician's role in prescribing trofinetide for Rett syndrome. Contemporary Pediatrics. September 5, 2024. Accessed December 9, 2024. https://www.contemporarypediatrics.com/view/the-pediatrician-s-role-in-prescribing-trofinetide-for-rett-syndrome