New Rett syndrome treatment approval

A huge congratulations to the Rett syndrome community for the recent approval of Trofinetide, a first-ever approved treatment for individuals living with Rett syndrome from Acadia Pharmaceuticals! Trofinetide is taken orally and acts to increase insulin-like growth factor 1 (IGF-1), a protein that is detected at low levels in an individual with Rett syndrome and necessary for brain development and plasticity. The primary clinical outcomes used to test Trofinetide’s ability to treat Rett syndrome were a clinician global impression scale (CGI-I) and a parent-reported behavior questionnaire, two relatively qualitative outcomes where small improvements (0.3 point improvement on CGI) resulted in drug approval. The largest improvements were in anxiety, rocking behavior, and hyporeactivity.

This is encouraging for the Angelman syndrome community, as it helps to define what success could look like as it relates to the clinical trial endpoints. This study utilized two measures as co-primary endpoints (CGI [clinician global impression of change] and a parent questionnaire of behavior in Rett syndrome). In Angelman syndrome we have developed similar types of endpoints specific to the domains that are considered most important by our community. It is also exciting to see a growth factor such as IGF1 being used in the treatment of Rett syndrome. This is similar to what we would call the 3rd Pillar, where a downstream target impacting the synapse is being targeted.

This is a monumental moment for the Rett syndrome community and the rare disorder world at large. A success such as this reverberates throughout the rare disorder space by increasing awareness, promoting both new and continued advancements in research, and paving the road for more clinical trial victories. We are thrilled for the Rett syndrome community, this is such heartening news and we hope that Angelman syndrome will be next!