Trofinetide

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Research highlights include trends in diagnosis, clinical phenotypes of males with MECP2 mutations, multidisciplinary approaches to understanding MECP2-related disorders, revised diagnostic criteria, and advancements in clinical trial readiness for therapeutic development. Studies also focus on genotype-phenotype relationships, mutation severity, and the development of evaluation tools and treatment trials for Rett syndrome.

A survey at the AES 2024 Annual Meeting found that 86% of prescribers reported titrating trofinetide improved tolerability in Rett syndrome patients, reducing diarrhea severity and treatment discontinuations, and enhancing quality of life for patients and caregivers.

Marvel Biosciences announced additional data from its preclinical Rett syndrome study, showing MB204's sustained benefits surpassing Trofinetide. MB204 exhibited strong carry-over effects for 21 days post-treatment, compared to Trofinetide's 14 days. Marvel plans to engage with the US FDA for orphan and/or rare disease designation, aiming for market exclusivity and priority review waivers.

Neurogene and Taysha Gene Therapies are developing gene therapies for Rett syndrome, with clinical trials in Phase 1/2. Neurogene's NGN-401 and Taysha's TSHA-102 aim to regulate MECP2 expression, crucial for treating the disorder. Despite a severe adverse event in Neurogene's high-dose trial, both companies remain optimistic about their therapies' potential to treat Rett syndrome at its source.

Marvel Biosciences reports MB204 showed 21-day post-treatment benefits in Rett syndrome, surpassing Trofinetide's 14-day effects. The company plans to seek FDA Orphan and rare disease designation for MB204, aiming for market exclusivity and other benefits. Full study results expected in Q1 2025.

Marvel Biosciences Corp. reported promising interim results from its MB204 study for Rett syndrome, showing near-normal social interaction restoration in a preclinical model. MB204 outperformed Trofinetide in most endpoints, with a distinct carry-over effect. Marvel aims to complete the study and publish the data.

Health Canada approves DAYBUE™ (trofinetide) as the first treatment for Rett syndrome in Canada, following positive Phase 3 LAVENDER study results.

Clinical trials for Rett syndrome need better outcome measures to objectively confirm symptom improvement. Existing measures lack specificity for motor and autonomic functions. Acadia Pharmaceuticals' Daybue became the first FDA-approved treatment, while Anavex Life Sciences' ANAVEX2-73 failed in Phase III. Experts advocate for a holistic approach including behavioural and biomarker assessments. Video motor assessments and wearable biosensors are suggested for more objective evaluations.

Pre-ordering for epinephrine nasal spray (neffy) has launched for treating allergic reactions, including anaphylaxis. The FDA approved trofinetide (Daybue) for Rett syndrome, marking a milestone in treatment. A study in JAMA Pediatrics found not all screen time before bed negatively impacts sleep in children. Another study in The American Journal of Clinical Nutrition linked fish intake during pregnancy to reduced autism risk in children.