Oct. 30, 2025 -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that the first patient has been dosed in the Aurora study (NCT07157254) evaluating the efficacy and safety of GTX-102 (apazunersen), an investigational antisense oligonucleotide (ASO) for Angelman syndrome (AS). Data from the Aurora study will expand the population of Angelman patients treated to include both younger and older patients and those with other non-deletion AS genotypes not included in the Phase 3 Aspire study. The fully enrolled Phase 3 Aspire study (NCT06617429) of GTX-102 is focused on patients aged 4 to 17 years with a genetically confirmed diagnosis of full maternal UBE3A gene deletion.
"The open-label basket design of the Aurora study will enable us to efficiently evaluate the safety and efficacy of GTX-102 in younger and older patients with Angelman syndrome and those with other genotypes," said Eric Crombez, M.D., chief medical officer at Ultragenyx. “While the Aspire study population represents the largest group of Angelman patients, we recognize the importance of bringing this potential new treatment to all patients, across genotypes and ages, as quickly as possible.”
Amanda Moore, chief executive officer at the Angelman Syndrome Foundation (ASF) and Ryan Fischer, chief operating officer at Foundation for Angelman Syndrome Therapeutics (FAST), added in a joint statement: "The launch of the Aurora trial marks an exciting and hopeful moment for the Angelman syndrome community. This study captures a broad spectrum of individuals living with Angelman syndrome and reflects a collective goal shared by our community—to ensure that clinical trial opportunities are available across ages and genotypes. We are grateful to Ultragenyx for their continued commitment to advancing research for our loved ones and for recognizing the importance of including a diverse population of individuals in clinical trials."
The global Aurora study will enroll approximately 60 participants ages 1 to Aspire Phase 3 study. Participants will be assigned to one of four cohorts with corresponding subprotocols:
Cohorts A, B, and C are single-arm only and in Cohort D participants will be randomized 2:1 to a GTX-102 group or a No Treatment group. All cohorts have a 48-week primary efficacy period; the No Treatment group will cross over to treatment receive their first loading dose of GTX-102 at Week 24. Participants from all cohorts have the option to continue treatment in a long-term extension study following their Aurora end of study visit.
In July 2025, enrollment for the global Phase 3 Aspire study was completed ahead of plan due to patient and investigator interest, with 129 participants ages four to 17 with a genetically confirmed diagnosis of full maternal UBE3A gene deletion randomized across 28 global sites. Data from the Aspire study are expected in the second half of 2026.
GTX-102 (apazunersen) is an investigational antisense oligonucleotide (ASO) therapy delivered via intrathecal administration and designed to target and inhibit expression of the UBE3A-AS to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein. GTX-102 has been granted Breakthrough Therapy Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA and Orphan Designation and PRIME designation from the EMA.
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 (CNS), 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-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 generally not inherited but instead occurs spontaneously. It is estimated to affect approximately 60,000 people in commercially accessible geographies.
Angelman syndrome is a lifelong neurodevelopmental disorder that 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 be 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, 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.
Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
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