Ultragenyx Announces Positive Interim Phase 1/2 Data in Patients with Angelman Syndrome After Treatment with GTX-102
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced new data from the Phase 1/2 study of GTX-102 for the treatment of Angelman syndrome. Patients in Expansion Cohorts A & B treated with a set dose and regimen of GTX-102 showed rapid and clinically meaningful improvement across multiple domains consistent with or exceeding Dose-escalation Cohorts 4-7 data at Day 170. Treatment of the Dose-escalation Cohorts 4-7 showed long-term increasing and sustained clinical benefit far exceeding Natural History data at Day 758. These data will be discussed in more detail in a corporate presentation being hosted by the company today at 8:00 a.m. ET and will also be presented by Kemi Olugemo, M.D., FAAN at the 76th Annual American Academy of Neurology Meeting (AAN) in Denver on Tuesday, April 16.
“There is currently no approved disease modifying treatment for Angelman syndrome, which results in profound impairment in individuals living with this disease,” said Erick Sell, M.D., director of the Angelman clinic at the Children’s Hospital of Eastern Ontario, and a principal investigator on the Phase 1/2 study. “The multidomain improvement in the Bayley-4 and ASA measures are significant and in line with the clinically meaningful change observed by patient families. These kids have continued to make functional gains over time, which may ultimately lead to more independence.”
New Expansion Cohorts A & B data include Day 170 results on 24 patients, and long-term Dose-escalation Cohorts 4–7 data include up to Day 758 results on 15 patients.
Expansion Cohorts at Day 170:
- Cognition assessed by Bayley-4 showed rapid and clinically significant improvement compared with Natural History data. Day 170 data were consistent with the treatment benefit observed in the Dose-escalation Cohorts at a similar timepoint.
- Behavior assessed by the Angelman Severity Assessment (ASA) showed rapid improvement exceeding the treatment benefit observed in the Dose-escalation Cohorts at Day 170.
- Hyperactivity and noncompliance assessed by the Aberrant Behavior Checklist-Community (ABC-C) showed rapid and clinically significant improvement at Day 170 compared with Natural History data, providing further insight into one of the most commonly reported behavioral issues.
- Sleep assessed by ASA showed rapid and clinically meaningful improvement exceeding treatment benefit observed in the Dose-escalation Cohorts at Day 170.
- Receptive communication assessed by Bayley-4 showed rapid improvement compared with Natural History data. Day 170 data were consistent with the treatment benefit observed in the Dose-escalation Cohorts at a similar timepoint.
- Gross Motor function assessed by ASA showed rapid improvement exceeding the treatment benefit observed in the Dose-escalation Cohorts at Day 170. Gross motor assessments as measured by Bayley-4 were not performed at Day 170 in the Expansion Cohorts to reduce patient testing burden and are not included in this analysis at this timepoint.
- Multi-domain Responder Index (MDRI) analysis across the four domains of Cognition, Receptive Communication, Behavior and Sleep resulted in a total net response of +2.0 (p-value <0.0001). The majority of patients had already achieved a total net response of +2 to +4 domains, demonstrating improvement exceeding the minimally important difference (MID) threshold in several domains even at this early Day 170 timepoint.
Dose-escalation Cohorts up to Day 758:
- Cognition assessed by Bayley-4 showed continuing long-term improvement compared with Natural History data and exceeded the threshold of clinical significance by many-fold in many patients.
- Behavior assessed by ASA showed continuing clinically meaningful improvement.
- Sleep assessed by ASA showed sustained clinically meaningful improvement.
- Receptive communication measured by Bayley-4 showed sustained and clinically significant improvement compared with Natural History data.
- Gross motor function assessed by Bayley-4 showed continued and clinically significant improvement compared with previously reported Natural History data.
- MDRI analysis across the four domains of Cognition, Receptive Communication, Behavior and Sleep resulted in a total net response of +2.0 (p-value = 0.0007) at Day 338. The majority of patients had a total net response of +2 to +4, as well as a 2- to 5-fold improvement over the MID threshold in several domains.
“The totality of these interim data demonstrates that treatment with GTX-102 resulted in rapid, multi-domain improvements that continued during maintenance dosing. These broad developmental gains are having a meaningful impact on patients and their families. For example, we’re hearing about children who are now able to routinely communicate their needs to family members, which greatly improves their ability to interact with their caregivers. We have also heard from families about their children who are accumulating additional developmental gains such as running, swimming and independent eating,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “Our next step is an end of Phase 2 meeting with the FDA and interactions with other health authorities to enable timely initiation of a Phase 3 pivotal study.”
There were no unexpected serious adverse events. Three patients had serious adverse events (mild to moderate) of lower extremity weakness assessed as related to study treatment; one in Cohort 7, two in Cohorts A & B; none reported in Cohorts C–E to date. All resolved rapidly without sequelae and remain in the study without ongoing safety concerns. The five original patients affected by lower extremity weakness from Cohorts 1–3 have been re-dosed safely multiple times and are receiving maintenance treatment without recurrence. The Cohort 7 patient has also been re-dosed safely multiple times and is receiving maintenance treatment without recurrence. The two patients in Cohorts A & B remain in study and are expected to continue dosing. The FDA and other regulatory agencies were notified of all safety events and raised no issues nor required additional actions. The foregoing safety information is current as of April 5, 2024.
Conference Call and Webcast Information
Ultragenyx will host a conference call at 8:00 a.m. ET today to discuss the new efficacy and safety data from the GTX-102 Phase 1/2 clinical study. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations.
