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

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

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jan 2024 ➔ Dec 2025 | Trial primary completion date: Feb 2023 ➔ Dec 2023

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=83 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | N=20 ➔ 83 | Trial completion date: Jan 2023 ➔ Jan 2024 | Trial primary completion date: Oct 2022 ➔ Feb 2023

Enrollment change • 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=20; Recruiting; Sponsor: GeneTX Biotherapeutics, LLC; Trial completion date: Jan 2022 ➔ Jan 2023; Trial primary completion date: Jan 2022 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Pediatrics

"$ACST Acasti Pharma Awarded Composition-of-Matter Patents for GTX-101 in Europe, China and Mexico and for GTX-102 in Japan https://t.co/RA4hXEQCTF #patent" (@stock_titan)

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2; N=20; Recruiting; Sponsor: GeneTX Biotherapeutics, LLC; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Pediatrics

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2; N=20; Active, not recruiting; Sponsor: GeneTX Biotherapeutics, LLC; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Anesthesia • Pediatrics

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2; N=20; Recruiting; Sponsor: GeneTX Biotherapeutics, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

KIK-AS: A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (clinicaltrials.gov) - P1/2; N=20; Not yet recruiting; Sponsor: GeneTx Biotherapeuics, LLC.

Clinical • New P1/2 trial