Ultragenyx announces results from interim Phase 1/2 data of GTX-102

Ultragenyx Pharmaceutical announced new data from the Phase 1/2 study of GTX-102 for the treatment of Angelman syndrome. 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 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 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 analysis across the four domains of Cognition, Receptive Communication, Behavior and Sleep resulted in a total net response of +2.0. The majority of patients had already achieved a total net response of +2 to +4 domains, demonstrating improvement exceeding the minimally important difference 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