FDA OKs first drug for Rett syndrome


The Food and Drug Administration has approved trofinetide oral solution (Daybue, Acadia Pharmaceuticals) as the first treatment of Rett syndrome in adults and children aged 2 years and older.

Rett syndrome is a rare, genetic neurodevelopmental disorder that affects about 6,000-9,000 people in the United States, mostly females.

Symptoms typically present between 6 and 18 months of age, with patients experiencing a rapid decline with loss of fine motor and communication skills.

A stamp saying "FDA approved." Olivier Le Moal/Getty Images

Trofinetide is a synthetic analogue of the amino-terminal tripeptide of insulinlike growth factor-1 (IGF-1), which occurs naturally in the brain. The drug is designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function.

The approval of trofinetide was supported by results from the pivotal phase 3 LAVENDER study that tested the efficacy and safety of trofinetide vs. placebo in 187 female patients with Rett syndrome, aged 5-20 years.

A total of 93 participants were randomly assigned to twice-daily oral trofinetide, and 94 received placebo for 12 weeks.

After 12 weeks, trofinetide showed a statistically significant improvement from baseline, compared with placebo, on both the caregiver-assessed Rett Syndrome Behavior Questionnaire (RSBQ) and 7-point Clinical Global Impression-Improvement (CGI-I) scale.

The drug also outperformed placebo at 12 weeks in a key secondary endpoint: the composite score on the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist-Social (CSBS-DP-IT Social), a scale on which caregivers assess nonverbal communication.

The most common adverse events with trofinetide treatment were diarrhea and vomiting. Almost all these events were considered mild or moderate.

‘Historic day’

“This is a historic day for the Rett syndrome community and a meaningful moment for the patients and caregivers who have eagerly awaited the arrival of an approved treatment for this condition,” Melissa Kennedy, MHA, chief executive officer of the International Rett Syndrome Foundation, said in a news release issued by Acadia.

“Rett syndrome is a complicated, devastating disease that affects not only the individual patient, but whole families. With today’s FDA decision, those impacted by Rett have a promising new treatment option that has demonstrated benefit across a variety of Rett symptoms, including those that impact the daily lives of those living with Rett and their loved ones,” Ms. Kennedy said.

Trofinetide is expected to be available in the United States by the end of April.

A version of this article first appeared on Medscape.com.

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