Rett syndrome (RTT) is a rare neurodevelopmental disorder primarily affecting females, characterized by symptoms such as loss of verbal communication, motor function, behavioral issues, seizures, and gastrointestinal problems. Until recently, treatment focused on managing individual symptoms due to the lack of an approved treatment for core symptoms.
Trofinetide, developed as a synthetic analog of GPE, has shown promise in addressing the core symptoms of RTT. The development of trofinetide was based on the discovery that GPE, a neuroactive tripeptide derived from insulin-like growth factor-1 (IGF-1), could partially rescue synaptic function in a MeCP2 mutant RTT mouse model. Trofinetide was designed to improve the proteolytic stability and bioavailability of GPE.
Clinical trials, including phase II and phase III studies, demonstrated the efficacy and safety of trofinetide in treating RTT. Notably, the LAVENDER study, a phase III trial, showed that trofinetide significantly improved core symptoms of RTT, as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scales. Trofinetide was well tolerated, with diarrhea and vomiting being the most common adverse events.
The approval of trofinetide by the FDA in March 2023 was the result of collaborative efforts between academia, the pharmaceutical industry, and patient advocacy groups like the International Rett Syndrome Foundation (IRSF). This collaboration facilitated the development of clinical trial endpoints, participant recruitment, and the overall advancement of trofinetide through the regulatory process.
The success of trofinetide's clinical program underscores the importance of coordinated efforts among researchers, pharmaceutical companies, and patient advocacy groups in developing treatments for rare diseases. The approval of trofinetide offers new hope for individuals with RTT and their families, providing a targeted treatment option for this challenging condition.
