UAB part of promising drug trial for Rett syndrome

A recently concluded study of an experimental drug for Rett syndrome showed promising results, according to the drug’s manufacturer, Neuren Pharmaceuticals of Melbourne, Australia. The University of Alabama at Birmingham was one of three study sites for the drug, known as NNZ-2566.

Neuren announced Nov. 12 that the Phase II study had achieved its primary endpoint as two dose levels of NNZ-2566 were tolerated well after 28 days of treatment and no safety concerns were identified. Further, the company reported that the higher of two doses studied exceeded the pre-specified criteria for improvement in core efficacy measures compared with placebo.

There are currently no approved medicines for the treatment of Rett syndrome, a severe neurological disorder caused by mutations of the MECP2 gene on the X chromosome. Rett syndrome is a post-natal neurological disorder that occurs almost exclusively in females following apparently normal development for the first six months of life. Typically, between 6 to 18 months of age, patients experience a period of rapid clinical decline that stabilizes later in life.

There are approximately 10,000 to 20,000 females with Rett syndrome in the United States and more than 50,000 worldwide.

“The results of this trial suggest a very promising proof of concept as we continue on the pathway to develop a disease-altering treatment for girls and women with Rett syndrome,” said Alan Percy, M.D., professor of pediatric neurology in the UAB School of Medicine and one of the trial investigators.

This was the first multisite, sponsor-led clinical trial in Rett syndrome and the first trial in an adolescent and adult population, according to Neuren. In addition to UAB, the other study sites were the Baylor College of Medicine and Gillette Children’s Specialty Healthcare.

"The results of this trial suggest a very promising proof of concept as we continue on the pathway to develop a disease-altering treatment for girls and women with Rett syndrome."

The study enrolled 53 subjects ages 16-45 years in the double-blind placebo-controlled trial. Two different dose levels of NNZ-2566 were tested: 35mg/kg twice per day and 70mg/kg twice per day. The dosage form was a strawberry-flavored liquid that was taken orally.

“These are exciting times for Rett syndrome, and this trial firmly sets our rudder in the water for the near future,” said Steven Kaminsky, Ph.D., the chief science officer for the International Rett Syndrome Foundation. “The results will enable engagement with the FDA on the further development of NNZ-2566. This is what we, as the Rett community, have been hoping for.”

Neuren indicates that they will submit applications to the U.S. Food and Drug Administration for both orphan drug and breakthrough therapy designations. Neuren expects to meet with the FDA in the first quarter of 2015 to discuss the trial results and the requirements for the further development of NNZ-2566 to treat Rett syndrome.