GTX-102, being evaluated for the treatment of Angelman syndrome (AS), filed with the U.S. Food and Drug Administration (FDA) is now active. Enrollment in a Phase 1/2 study is expected to begin in the first half of 2020.
The phase 1/2 study, named KIK-AS (Knockdown of UBE3A-antisense in Kids with AS, is expected to enroll 20 patients at multiple trial sites, beginning in the first half of 2020. The goal of this multiple dose, dose escalating, open-label study is to examine the safety, tolerability, and pharmacokinetics of GTX-102 in pediatric patients with Angelman syndrome. On February 15, 2020 the company will open a website with more information on the KIK-AS study and provide a toll-free number for parents and caregivers to obtain information on enrolling into the clinical study.
GTX-102 has been granted Orphan Drug Designation and Rare Pediatric Disease Designation from the U.S. FDA.
GeneTx and Ultragenyx announced a partnership to develop GTX-102 in August of 2019, with Ultragenyx receiving an exclusive option to acquire GeneTx.
About Angelman Syndrome
Angelman syndrome is a rare, neurogenetic disorder 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. Silencing of the paternal UBE3A allele is regulated by the UBE3A antisense transcript (UBE3A-AS), the intended target of GTX-102. In almost all cases of Angelman syndrome, the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression. This condition is typically not inherited but instead occurs spontaneously.
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. Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. Angelman syndrome is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this 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 antisense oligonucleotide 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.