RARE Daily

FDA Awards GeneTx and Ultragenyx Fast Track Designation for Angelman ASO

May 4, 2020

Rare Daily Staff

The U.S. Food and Drug Administration granted GeneTx Biotherapeutics and Ultragenyx Pharmaceutical Fast Track designation for their experimental antisense oligonucleotide therapy GTX-102 for the treatment of the rare neurogenetic disorder Angelman syndrome.

Individuals with Angelman syndrome have developmental delay, balance issues, motor impairment, and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. While individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. The condition is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome.

Angelman syndrome is caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system, a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not.

GTX-102 is an investigational antisense oligonucleotide currently being evaluated in a phase 1/2 study for the treatment of Angelman syndrome. It is designed to target and inhibit expression of UBE3A-AS. Nonclinical studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. Reactivation of paternal UBE3A expression in animal models of Angelman syndrome has been associated with improvements in some of the neurological symptoms associated with the condition.

In August 2019, GeneTx and Ultragenyx announced a partnership to develop GTX-102, with Ultragenyx receiving an exclusive option to acquire GeneTx.

The FDA’s Fast Track designation is a program designed to facilitate the development and expedite the review of drugs intended to treat serious conditions that demonstrate the potential to address an unmet medical need. Fast Track designation allows for early and frequent communication with the FDA throughout the entire drug development and review process and allows for a rolling review of a company’s New Drug Application (NDA). Products with Fast Track designation may also be eligible for Priority Review, if relevant criteria are met at the time of NDA filing.

The FDA previously granted GTX-102 Orphan Drug designation and Rare Pediatric Disease designation.

“GeneTx is committed to improving the quality of life of individuals living with Angelman syndrome,” said Paula Evans, CEO of GeneTx. “Receiving Fast Track designation for GTX-102 is an important recognition of our antisense oligonucleotide program and the promise it might offer to this patient population.”

Photo: Paula Evans, CEO of GeneTx



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