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Taking aim on Angelman
SARASOTA, Fla.—GeneTx Biotherapeutics LLC announced today that it has received institutional review board (IRB) approval from Rush University Medical Center to begin the “KIK-AS” (Knockdown of UBE3A-antisense in Kids with Angelman Syndrome) Phase 1/2 clinical study of GTX-102. GTX-102 is an experimental antisense oligonucleotide being evaluated for the treatment of Angelman syndrome (AS).
Angelman syndrome is a rare neurogenetics 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. 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; it occurs spontaneously.
People 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 with Angelman syndrome. While those with Angelman syndrome have a normal lifespan, they typically require continuous care and cannot live independently.
“A tremendous amount of basic research over decades, and intense research and development over the last couple of years has now brought us to the cusp of testing a novel drug in individuals with Angelman syndrome,” stated Scott Stromatt, M.D., chief medical officer of GeneTx Biotherapeutics. “This is truly an exciting time for patients, families and medicine.”
GTX-102 is an investigational antisense oligonucleotide which is designed to target and inhibit expression of UBE3A-AS. Nonclinical studies have shown 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.
The objective of this Phase 1/2 open-label, multiple-dose, dose-escalating study is to evaluate the safety, tolerability, and plasma and cerebrospinal fluid (CSF) concentrations of GTX-102 in pediatric patients with Angelman syndrome. Approximately 20 patients (male and female) ≥ 4 and ≤ 17 years of age with a genetically confirmed diagnosis of full maternal UBE3A gene deletion will be enrolled. Further details about the study can be found here.
“The GeneTx team continues to make significant progress in advancing the GTX-102 program for patients with Angelman Syndrome, and we look forward to continuing our work with the team to move this program into the clinic,” said Camille L. Bedrosian, M.D., chief medical officer of Ultragenyx Pharmaceutical, a biopharmaceutical company which has partnered with GeneTx to develop GTX-102.
GTX-102 has been granted Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA). GeneTx and Ultragenyx announced their partnership to develop GTX-102 in August 2019, in which Ultragenyx received an exclusive option to acquire GeneTx. Rush University Medical Center in Chicago will be the first center to enroll patients for the trial, with additional sites planned for Boston, Cincinnati, Denver, Los Angeles, New York and Ottawa, Canada.