ANGELMAN SYNDROME PHASE 3 TRIALS — COMMUNITY UPDATE (Webinar recorded: 4 Sep 2025)
Video here: https://youtu.be/TenTbLp9pIk
WHO HOSTED
• FAST
• ASA
ULTRAGENYX — GTX-102 (antisense oligonucleotide targeting UBE3A-ATS)
• Phase 1/2 (open-label; ages 4–17, maternal deletion; data cut Sep 2024)
– Signals of improvement vs natural history in cognition (Bayley-4), receptive communication, sleep, gross motor, and behavior (ABC-C).
– Multi-Domain Responder Index: 79% improved in at least 1 domain.
– Safety: early lower-extremity weakness at higher doses resolved; mitigation in place; no new cases since; participants re-dosed without recurrence.
• Phase 3 — ASPIRE
– Population: 4–17, maternal deletion; sham-controlled with 1-year crossover.
– Status: fully enrolled (July 2025).
• Phase 2 — AURORA (planned start before end of 2025)
– Population: all genotypes; under 4 years and over 18 years.
– Sites: mix of experienced and new; activations posted on clinicaltrials.gov.
• Long-Term Extension: opened summer 2024; all GTX-102 participants continue on treatment.
• Contact for site matching/questions: trialrecruitment@ultragenyx.com
IONIS — ION-582 (antisense oligonucleotide targeting UBE3A-ATS)
• Background: RNA-targeted medicine designed to unsilence paternal UBE3A by reducing UBE3A-ATS.
• Phase 1/2 — HALO (ongoing)
– Around 50 participants, ages 2–50, deletion or mutation; all in long-term extension.
– Planned 2025 addition: cohort under 2 years at existing HALO sites (includes EU).
• Phase 3 — REVEAL (global; started May 2025)
– About 200 participants, ages 2–50, deletion or mutation.
– Design: randomized, double-blind, placebo-controlled; intrathecal dosing every 3 months (40 mg or 80 mg vs placebo in Year 1); all receive active drug in Years 2–3.
– Primary endpoint: expressive communication (Bayley-4). Key secondaries: cognition, receptive communication, disease severity, sleep, motor, daily living skills.
– Safety oversight: independent monitoring committee.
– Status: first sites opened in the US; more US and global sites coming (posted as activated on clinicaltrials.gov).
PRACTICAL NOTES (applies broadly)
• How to enroll: speak with your clinician; site investigators determine eligibility. Sponsors do not keep waitlists. Use clinicaltrials.gov for active sites; FAST/ASA can help you prepare.
• Europe timing: no specific dates promised; sites open on a rolling basis and appear on clinicaltrials.gov when fully activated.
• Younger patients: Ultragenyx AURORA will include under-4s; Ionis HALO adding under-2 cohort at existing sites (including EU).
• While in a trial: concurrent participation in other trials is generally not allowed; after a trial ends it’s case-by-case—ask your site investigator.
• Daily life: participants are expected to continue normal school/preschool and may travel; must attend scheduled visits. Carry site contact info and your trial ID card when traveling.
• Administration: both programs use intrathecal dosing (lumbar puncture under sedation).
WHERE TO CHECK FOR UPDATES
• clinicaltrials.gov (search: GTX-102, ION-582, ASPIRE, AURORA, HALO, REVEAL)
• FAST and ASA channels for community news and how-to resources
Disclaimer: These are investigational medicines; safety/efficacy are still being evaluated by ongoing trials and regulatory authorities. Always discuss decisions with your medical team.
Video on: https://youtu.be/TenTbLp9pIk