Update on the GTX-102 program for Angelman Syndrome

Quick Overview

Dr. Kemi Olugemo provided an update on the GTX-102 program for Angelman Syndrome during the 2023 FAST Science Summit. The program is currently in Phase 2 and is showing promising results in improving cognition, receptive communication, gross motor skills, sleep, and behavior in patients. The data from the trial indicate a significant separation from natural history, and the changes in the Bayley assessments were associated with a reduction in delta power on EEG and increased sleep duration. Patients who had a pause in treatment and were re-dosed showed regained skills after resuming the drug. Safety data showed mostly procedure-related adverse events. The next steps for the program include completing enrollment of expansion cohorts, phase 3 planning, and exploring the inclusion of non-deletion patients and younger patients in future trials.


Dr. Kemi Olugemo, Vice President of Global Clinical Development at Ultragenyx, will be providing an update on the GTX-102 program in Angelman Syndrome. This update comes after recent exciting news via a press release, and today we will get the opportunity to hear more about the progress made so far.

Mission of Ultragenyx

Ultragenyx, founded 13 years ago by Emil Kakkis, has a mission to transform the lives of patients living with rare and ultra-rare diseases. The company has been prolific in getting drugs into trials and making improvements in various therapeutic areas, including bone and endocrine, metabolic, and neuroscience.

About Angelman Syndrome and GTX-102

Angelman Syndrome falls under the neuroscience category, and GTX-102 is an investigational drug being developed by Ultragenyx. It is an antisense oligonucleotide (ASO) administered intrathecally. The current trial is in Phase 2 and focuses on safety, pharmacokinetics, and clinical activity. The trial assesses various domains critical to individuals, particularly pediatric patients, living with Angelman Syndrome, including communication, sleep, behavior, motor skills, and seizures.

Study Design and Eligibility Criteria

The Phase 2 trial is a first-in-human open-label dose-escalating study. Patients receive loading doses one month apart, followed by a maintenance period every three months. Patients can remain on the drug until the program is discontinued or the drug is commercially available. The trial currently includes patients with deletion and aged between 4 and 17 at screening. Patients must have normal kidney and liver function and be able to tolerate anesthesia for lumbar puncture.

Phase 2 Data

Dr. Olugemo presented Phase 2 data from a select group of patients who have the largest body of longitudinal data. These patients received maintenance doses up to 14 milligrams. The data showed improvements in various domains, including cognition, receptive communication, gross motor skills, sleep behavior, and overall scores. The improvements exceeded the threshold of significance and showed a significant separation from natural history data.

EEG and Biomarkers

The study also looked at EEG data and found a reduction in delta power, which is associated with cognitive improvement. The changes in EEG delta waves correlated with improvements in cognition scores. This suggests the potential of EEG as a biomarker for use in Angelman Syndrome.

Patients Who Were Redosed

The study included patients who were redosed after a pause of approximately two years. These patients regained the skills they had lost during the pause when they resumed the drug at a lower dose. The regained skills included improved communication, behavior, sleep, and motor skills.

Safety Data

The safety data for all patients in the trial showed that most adverse events were related to procedures, such as lumbar puncture or anesthesia. There were no unexpected adverse events or new safety concerns since the last update. Patients received up to 11 consecutive doses of GTX-102.

Next Steps

The study will complete enrollment of expansion cohorts and expects to have data in the first half of next year. Phase 3 planning is ongoing, and the company will communicate the timing for including patients currently excluded from the trial, such as non-deletion patients and younger patients.


The interim Phase 2 data for GTX-102 in Angelman Syndrome showed improvements in various domains, exceeding the threshold of significance and separating from natural history data. The study also found correlations between EEG changes and cognitive improvements. Patients who were redosed regained the skills they had lost during the pause. The safety data showed no unexpected adverse events. Ultragenyx plans to continue developing GTX-102 and include more patient groups in future trials.


Dr. Olugemo expressed gratitude to the clinical team, families, sites, investigators, and the entire community for their efforts in participating in trials and natural history studies. She also thanked FAST for their support.

Talk details

  • Title: Update on the GTX-102 program for Angelman Syndrome
  • Author(s): Kemi Olugemo
  • Author(s)’ affiliation: Ultragenyx
  • Publication date: 2023-11-12
  • Collection: 2023 FAST Science Summit