Furthermore, the treatment is safe and well tolerated, according to results published online ahead of print March 27 in Neurology.
“These are very promising data for the Rett community that is currently without any [Food and Drug Administration]–approved treatment option,” Daniel Glaze, MD, said in a press release from Acadia Pharmaceuticals, which is developing trofinetide.
In 2017, a phase 2 study indicated that the drug was safe and tolerable when administered in doses of 70 mg/kg b.i.d. to adolescent and adult females with Rett syndrome. The study also provided initial evidence of the drug’s efficacy. Dr. Glaze, professor of pediatrics and neurology at Baylor College of Medicine in Houston, and his colleagues decided to conduct a larger phase 2 study that examined higher doses and a longer treatment duration.
The researchers first enrolled 62 participants in the study, all of whom received placebo b.i.d. for 14 days. They next randomized participants in equal groups to placebo or one of three twice-daily doses of trofinetide (i.e., 50 mg/kg, 100 mg/kg, and 200 mg/kg). After a blinded review of safety and tolerability data, Dr. Glaze and his colleagues enrolled 20 more participants and randomized them in equal groups to placebo or 200 mg/kg b.i.d. of trofinetide. This modification in study design was intended to increase the likelihood of detecting a clinical benefit. Randomized, double-blind treatment lasted for 42 days. Participants presented for a final visit at approximately 10 days after the treatment period ended.
A total of 82 girls aged 5-15 years participated in the study. They all met the 2010 diagnostic criteria for classic Rett syndrome, had a documented pathogenic MECP2 variant, were in the postregression stage of the syndrome, and had been stable on pharmacologic and behavioral treatments for at least 4 weeks. The sample’s mean age was 9.7 years, 94% were white, and mean weight was 26.1 kg. The treatment groups’ demographic characteristics were balanced.