Health Canada has approved Daybue (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients aged two years and older, weighing at least 9 kg, marking a significant milestone as the first approved therapy for this rare neurodevelopmental disorder in Canada. The approval, granted under the Priority Review process, is based on data from the Phase 3 LAVENDER study, which demonstrated statistically significant improvements in key behavioral and communication measures compared to placebo.
Clinical Trial Data Supporting Approval
The pivotal Phase 3 LAVENDER study evaluated the efficacy and safety of trofinetide versus placebo in 187 girls and young women aged 5 to 20 years with Rett syndrome. The co-primary endpoints were the change from baseline in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) scale score at week 12. Both endpoints showed statistically significant improvements with trofinetide compared to placebo.
Additionally, a key secondary endpoint, measuring the change from baseline to week 12 in the Communication and Symbolic Behavior Scales Development Profile Infant-Toddler Checklist – Social Composite Score (CSBS-DP-IT Social), also demonstrated statistically significant improvement compared to placebo.
Mechanism of Action and Administration
Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1. While the precise mechanism by which trofinetide exerts its therapeutic effects in Rett syndrome is not fully understood, it is believed to lessen inflammation and promote healthy connections between nerve cells, helping to normalize brain activity. Daybue is administered orally, either directly or via a feeding tube, on a daily basis.
Impact on the Rett Syndrome Community
Rett syndrome is a rare, complex neurodevelopmental disorder primarily affecting females, characterized by a period of normal development followed by regression, leading to impairments in communication, motor skills, and repetitive hand movements. The prevalence of Rett syndrome in Canada is estimated to be between 600 and 900 individuals. Until now, treatment options have primarily focused on managing symptoms.
Catherine Owen Adams, CEO of Acadia Pharmaceuticals, stated, “Health Canada’s authorization of DAYBUE is a significant milestone for the Rett syndrome community in Canada and another step forward in Acadia’s commitment to increase access to this therapy for patients and their families.”
Dr. Anita Datta, Pediatric Neurologist at BC Children’s Hospital, noted, “Rett syndrome is a debilitating and complex neurodevelopmental disorder that presents differently across patients and can lead to a range of symptoms throughout a patient’s life. Until now, treatment options have primarily focused on symptomatic management, as specific therapies for Rett syndrome have not existed.”
Sabrina Millson, President of the Ontario Rett Syndrome Association (ORSA), added, “Today’s news is a historic milestone for the Canadian Rett syndrome community, who have eagerly awaited an approved treatment. Now that this therapy has been approved, we hope it will be made accessible through private and publicly funded drug plans as quickly as possible for all those who could benefit from it.”
Ongoing Commitment
Acadia Pharmaceuticals plans to work to bring Daybue to Canadian patients as quickly as possible. The company has also announced plans to seek approvals in other markets, including Europe and Japan.
