FDA Grants Ultragenyx Breakthrough Therapy Designation for Experimental Angelman Syndrome Therapy

Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation to Ultragenyx Pharmaceutical’s GTX-102, its experimental treatment for the rare neurodevelopmental condition Angelman syndrome.

Angelman syndrome causes cognitive impairment, motor impairment, balance issues, and debilitating seizures. Some individuals with Angelman syndrome are unable to walk, and most do not speak. Anxiety and disturbed sleep can create serious challenges in individuals with Angelman syndrome. Although individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. Angelman syndrome is not a degenerative disorder; however, the loss of UBE3A protein expression in neurons results in abnormal communication between neurons. The condition is often misdiagnosed as autism or cerebral palsy.

There are currently no approved therapies for Angelman syndrome; however, several symptoms of the disorder can be reversed in adult animal models of Angelman syndrome, suggesting that improvement of symptoms can potentially be achieved at any age.

GTX-102 is an experimental antisense oligonucleotide therapy delivered via intrathecal administration and designed to target and inhibit expression of the UBE3A antisense transcript to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein. The FDA previously granted GTX-102 Orphan Drug designation, Rare Pediatric Disease designation, and Fast Track designation from the FDA and Orphan Designation. The European Medicines Agency granted GTX-102 PRIME designation.

The FDA’s decision is based on preliminary clinical evidence including positive data from the Phase 1/2 study in 74 patients (4-17 years of age) with a full maternal UBE3A gene deletion, that showed participants have made consistent developmental gains with rapid, sustained and continuing improvements across multiple symptom domains when treated for up to 3 years. Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat serious or life-threatening diseases and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing therapies.

“FDA Breakthrough Therapy Designation underscores both the urgent need for an effective treatment for patients and families affected by Angelman syndrome and the clinically meaningful results demonstrated to date with GTX-102,” said Eric Crombez, chief medical officer at Ultragenyx. “Based on the strength of the phase 2 data and with strong support and interest from the Angelman syndrome community, our phase 3 Aspire study is rapidly enrolling across our global sites.”

Photo: Eric Crombez, chief medical officer at Ultragenyx