Neurological

Trofinetide shows promise in patients with Rett syndrome

Positive topline results were reported from a phase 3 study investigating trofinetide in Rett syndrome, a rare debilitating neurological disorder caused by mutations in the MECP2 gene.

Trofinetide is a novel synthetic analog of the amino terminal tripeptide of IGF-1 that was developed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and aiding synaptic function. The randomized, double-blind, placebo-controlled Lavender study (ClinicalTrials.gov Identifier: NCT04181723) evaluated the efficacy and safety of trofinetide in 187 women, ages 5 to 20 years old, with Rett syndrome.

Patients were randomized to receive trofinetide or placebo orally or via gastrostomy tube twice daily for 12 weeks. The co-primary endpoints were change from baseline to week 12 in the Rett Syndrome Behavioral Questionnaire (RSBQ) total score (a nurse assessment) and the Clinical Global Impression-Improvement (CGI-I) score (a doctor’s assessment) .

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The results showed that treatment with trofinetide showed a statistically significant improvement in RSBQ of -5.1 compared to -1.7 for placebo (P = 0.0175; effect size = 0.37). A statistically significant improvement over placebo was also observed in the CGI-I (3.5 vs 3.8; P = 0.003; effect size = 0.47).

Trofinetide also met an important secondary endpoint showing a statistically significant improvement from baseline by week 12 on the Developmental Profile Infant-Toddler Checklist-Social Composite Score communication and symbology behavior compared to placebo (-0.1 vs -1.1 ; P = 0.0064; effect.). Size = 0.43).

“Patients reported improvements in core symptoms, such as being able to respond to a decision made by their parents or experiencing more freedom from the repetitive hand movements that are obstacles in other areas of their lives,” said Jeffrey L. Neul, MD. PhD, Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center; Professor of Pediatrics, Department of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and investigator of the Lavender Study.

The most common side effects of trofinetide and placebo were diarrhea (80.6% vs. 19.1%) and vomiting (26.9% vs. 9.6%). The trofinetide arm had higher dropout rates associated with treatment-related side effects than the placebo arm (17.2% and 2.1%, respectively).

Patients who completed the Lavender study were able to resume treatment with trofinetide in the Lilac (ClinicalTrials.gov Identifier: NCT04279314) and Lilac-2 open-label extension studies.

The Food and Drug Administration (FDA) previously granted trofinetide Fast Track and Orphan Drug status for this indication. The company plans to file a new drug application with the FDA in mid-2022.

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Acadia Pharmaceuticals Announces Positive Top-Line Results from pivotal Phase 3 Lavender Trial of Trofinetide in Rett Syndrome. Press release. Acadia Pharmaceuticals Inc., accessed December 7, 2021. https://www.businesswire.com/news/home/20211206005778/en/Acadia-Pharmaceuticals-Announces-Positive-Top-line-Results-from-the-Pivotal-Phase – 3-Lavender-Trial-of-Trofinetide-in-Rett Syndrome.

This article originally appeared on MPR

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