Rett syndrome is a neurological disorder that occurs almost exclusively in females following apparently normal development for the first six months of life. Typically, between 6 to 18 months of age, patients experience a period of rapid decline with loss of purposeful hand use and spoken communication. Many patients have recurrent seizures. They experience a variety of motor problems including increased muscle tone (spasticity) and abnormal movements. These individuals are never able to provide fully for their own needs, with most requiring life-long medical care and 24 hour a day supportive care as they grow older. Most Rett syndrome patients live well into adulthood. In addition to direct costs for medical and related services – estimated to average more than US$20,000 per patient per year – costs for institutional and special education services as well as the financial and emotional impact on families are very large. It is a rare disorder and is believed to be second only to Down syndrome as a genetically-determined cause of chronic neurological problems in females that include severe communication, motor disabilities and epilepsy. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. There are more than 200 different mutations found on the MECP2 gene that interfere with its ability to generate a normal gene product. Rett syndrome strikes all racial and ethnic groups and occurs worldwide in approximately 1 in every 10,000 live female births.
Neuren conducted a Phase 2 double-blind placebo-controlled clinical trial in subjects aged 16 to 45 years with Rett syndrome, in which treatment with trofinetide showed clinical improvement in many of the core symptoms of Rett syndrome. The benefit was observed in both clinician and caregiver assessments. A Phase 2 trial is currently being conducted in subjects aged 5 to 15 years to test higher doses in this younger population and to confirm the optimum doses for a susequent Phase 3 trial in subjects aged 5 to 45 years.
The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both granted Orphan Drug designation to Neuren for trofinetide in Rett syndrome. The FDA has also granted Fast Track designation.
Rettsyndrome.org (International Rett Syndrome Foundation, or IRSF) has provided advice to Neuren on clinical trial strategy, introductions to leading clinical investigators and grant towards the cost of Neuren’s Rett syndrome trials. Support from an advocacy organisation such as IRSF in discussions with the FDA and communications with patients, families and investigators is an important factor assisting with the successful implementation of Neuren’s development programs.