apazunersen (GTX-102) / Foundation for Angelman Syndrome Therap, Ultragenyx - LARVOL DELTA

GTX-102-CL 302: Long-term Extension of GTX-102 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=255 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed

Aurora: A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS) (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Pediatrics

Aurora: A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

Pan tumor • Trial initiation date • Pediatrics

Aurora: A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

Pan tumor • Trial initiation date • Pediatrics

Emerging disease-modifying therapies for Angelman syndrome: A comprehensive review for pediatric neurologists. (PubMed, Brain Dev) - "The molecular pathophysiology of AS, natural history considerations critical for trial interpretation, and the current evidence for antisense oligonucleotide (ASO) therapies (ION582, GTX-102/apazunersen, rugonersen), gene replacement approaches (MVX-220), and next-generation strategies including CRISPR-based gene editing, artificial transcription factors, small molecules, and novel delivery platforms are reviewed. Critical challenges include outcome measurement limitations, genotype stratification, long-term safety monitoring, and ensuring equitable access. These advances herald a transformation in AS clinical care and represent a milestone in precision pediatric neurology."

Journal • Review • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Mental Retardation • Movement Disorders • Pediatrics • UBE3A

Results From a Phase 1/2 Open-label Trial of GTX-102, an Investigational Antisense Oligonucleotide for Treatment of Patients With Angelman Syndrome (ACMG 2026) - P1/2 | "Mitigation measures, including lower GTX-102 doses, dexamethasone premedication, aCSF flush immediately after GTX-102 administration, and post-flush Trendelenburg positioning significantly reduced LEW incidence from 100% (5/5) in early high-dose cohorts to 4% (3/69) in subsequent lower-dose cohorts. Treatment with GTX-102 resulted in rapid and progressive improvement in Bayley-4 Cognitive/Receptive Communication and ABC-C Hyperactivity/Noncompliance at D338. Phase 3 relevant doses and mitigation procedures resulted in a much lower incidence of LEW, and no new safety concerns were identified. Lower GTX-102 doses and administration mitigation measures were advanced into a pivotal Phase 3 GTX-102 trial."

Clinical • P1/2 data • CNS Disorders • Developmental Disorders • Sleep Disorder • UBE3A

GTX-102-CL210: A Safety and Efficacy Study of GTX-102 in Subjects with Deletion- or Nondeletion-type Angelman Syndrome (Aurora) (clinicaltrialsregister.eu) - P1/2 | N=19 | Not yet recruiting | Sponsor: Ultragenyx Pharmaceutical Inc.

New P1/2 trial • Pan tumor • Pediatrics

GTX-102-CL 302: Long-term Extension of GTX-102 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=255 | Enrolling by invitation | Sponsor: Ultragenyx Pharmaceutical Inc | N=75 ➔ 255

Enrollment change

Aurora: A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Pan tumor • Pediatrics

Aurora: A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

New P2 trial • Pan tumor • Pediatrics

Aspire: Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With Angelman Syndrome (AS) (clinicaltrials.gov) - P3 | N=129 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Pediatrics

Ultragenyx Receives Breakthrough Therapy Designation for GTX-102 in Angelman Syndrome (GlobeNewswire) - "Ultragenyx Pharmaceutical Inc...announced that it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for GTX-102 (apazunersen) as a treatment for Angelman syndrome....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 • Genetic Disorders • Rare Diseases

Disruption of UBE3A-ATS by Gene Editing with a Type V CRISPR-Cas Enzyme as a treatment for Angelman Syndrome (ASGCT 2025) - "Finally, 8 guides paired with two nucleases (ABR-001 and ABR-004) demonstrated UBE3A recovery equal to or greater than that of a benchmark ASO (GTX-102) in Angelman patient neurons, including 5 guides that reached UBE3A levels equivalent to neurotypical controls...Taken together, these results demonstrate the feasibility of using a Type V CRISPRCas enzyme to durably treat Angelman Syndrome. Disease Focus of Abstract:Inherited Neurological Disorders"

CNS Disorders • SNHG14 • UBE3A

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children with Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=74 | Completed | Sponsor: Ultragenyx Pharmaceutical Inc | Active, not recruiting ➔ Completed

Trial completion • Pediatrics • UBE3A

Aspire: Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With AS (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Pediatrics

Ultragenyx Announces First Patient Dosed in Pivotal Phase 3 Aspire Study Evaluating GTX-102 in Angelman Syndrome (GlobeNewswire) - "Ultragenyx Pharmaceutical...announced that the first patient has been dosed in the pivotal Phase 3 Aspire study (NCT06617429) evaluating the efficacy and safety of GTX-102, its investigational antisense oligonucleotide (ASO) for Angelman syndrome....The global Phase 3 Aspire study will enroll approximately 120 children ages 4 to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Participants will be randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group during the 48-week primary efficacy analysis period."

Trial status • Genetic Disorders • Rare Diseases

Advancing Therapeutic Frontiers for Angelman Syndrome: Insights From a Systematic Review (ISPOR-EU 2024) - "A dose-finding study of GTX-102, an antisense oligonucleotide therapy, highlighted improvements in symptoms and skill acquisition on the CGI-I-AS in five patients but was paused due to serious adverse events...Gaboxadol, minocycline, and levodopa were all observed to be well-tolerated... This review illustrates the challenges and potential of current pharmacological and non-pharmacological interventions in managing AS. While some pharmacological treatments show promise, the efficacy varies, highlighting the importance of integrating diverse therapeutic approaches. Continued innovation, particularly in genetic therapies and integrative treatment models, along with rigorous testing, are essential to develop more effective strategies for AS."

Review • CNS Disorders • Developmental Disorders • Gene Therapies • Pediatrics • Psychiatry • UBE3A

Aspire: Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With AS (clinicaltrials.gov) - P3 | N=120 | Not yet recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

New P3 trial • Pediatrics

GTX-102-CL 302: Long-term Extension of GTX-102 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=75 | Enrolling by invitation | Sponsor: Ultragenyx Pharmaceutical Inc | Not yet recruiting ➔ Enrolling by invitation

Enrollment open

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Dec 2025 ➔ Dec 2024 | Trial primary completion date: Dec 2025 ➔ Dec 2024

Trial completion date • Trial primary completion date • Pediatrics • UBE3A

Long-term Extension of GTX-102 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=75 | Not yet recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

New P3 trial

Clinical Activity and Safety of GTX-102, an Investigational Antisense Oligonucleotide for the Treatment of Patients With Angelman Syndrome (AAN 2024) - P1/2 | "Across the dose-escalation cohorts, participants had significant improvements in Bayley4 Receptive Communication, Cognition, and Gross Motor domains and quantitative improvement in EEG relative delta power and sleep. Additional results from the dose-expansion cohorts up to maintenance dose 2 (Study Day 254) will be reported."

Clinical • Late-breaking abstract • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Psychiatry • Sleep Disorder • UBE3A

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Pediatrics • UBE3A

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

Trial completion date • Trial primary completion date • Pediatrics • UBE3A

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial primary completion date: Dec 2023 ➔ Dec 2025

Trial primary completion date • Pediatrics • UBE3A