Ponni Subbiah, MD, MPH, Senior Vice President Global Head of Medical Affairs and Chief Medical Officer, Acadia Pharmaceuticals, discusses trofinetide for the treatment of Rett syndrome.
Overview of Rett Syndrome
Rett syndrome is a neurodevelopmental condition that primarily affects young girls. Genetic mutations in the MECP2 gene are usually the cause. People with the disease appear to have normal psychomotor development during the first 6 to 18 months of life. This is followed by a developmental “plateau,” and then rapid regression in language and motor skills. The severity of Rett syndrome may vary.
Additional symptoms may include
- repetitive, stereotypic hand movements
- fits of screaming and inconsolable crying
- autistic features
- panic-like attacks
- teeth grinding (bruxism)
- episodic apnea and/or hyperpnea
- gait ataxia and apraxia
- tremors
- seizures
- slowed head growth
Trofinetide Approval
In March 2023, the FDA approved Daybue (trofinetide) to treat Rett syndrome in children aged two and older. The drug was launched in April 2023, accompanied by resources for clinicians and caregivers. The positive response from the Rett community was notable, with initial uptake in Academic Centers of Excellence and subsequent expansion to various institutions and smaller healthcare practices over several months.
Clinical Studies
Subbiah describes the three critical studies testing the efficacy and safety of trofinetide that helped lead to its approval and quick acceptance in the community. The pivotal LAVENDER study, a 12-week trial, demonstrated both efficacy and safety. Participants from this study joined the open-label LILAC-1, a 40-week study, where continued improvement on primary endpoints was observed, maintaining a safety profile similar to the initial phase 3 study.
The third study, LILAC-2, presented at the American Epilepsy Society meeting, spanned 32 months with 77 participants. Safety outcomes included common events like diarrhea, COVID-19 infection, and vomiting, consistent with previous studies. Importantly, no new safety concerns emerged. Efficacy persisted, with improvements noted in caregiver and clinician-rated scales. In summary, LILAC-2 demonstrated the long-term efficacy and safety of trofinetide for Rett syndrome without new concerns, reinforcing its positive profile.
Caregiver Exit Interview Survey
The caregiver exit interview survey was part of the LILAC-2 study. Conducted with 27 caregivers, it aimed to understand drug benefits from their perspective. Using qualitative phone interviews, caregivers discussed observed improvements in their child’s engagement, hand use, eye gaze, communication, and interaction with others. The results provided insights beyond traditional trial endpoints, aligning with the FDA’s emphasis on incorporating patient and caregiver voices in drug development.
As Subbiah discusses, caregivers expressed alignment with key areas of improvement they sought in a drug, such as communication, hand use, walking, and seizure reduction. The study demonstrated that trofinetide addressed these areas, leading to improved physical and social functioning in children. Additionally, 54% of caregivers reported a positive impact on their own lives, including increased family happiness, enhanced participation in social gatherings, and improved parent-child interactions.
For more information on Rett syndrome, visit our learning page at https://checkrare.com/rett-syndrome/
