Rare Disease-Focused-Ultragenyx Pharmaceutical Stock Falls On Serious Adverse Events In Eaarly Genetic Disorder Study

Monday, Ultragenyx Pharmaceutical Inc RARE revealed new data from the Phase 1/2 study of GTX-102 for Angelman syndrome, a genetic disorder causing developmental disabilities and nerve-related symptoms.

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 benefits far exceeding Natural History data at Day 758. 

Expansion Cohorts at Day 170 on 24 patients:

• Cognition and receptive communication showed rapid and clinically significant improvement compared with Natural History data. 
•  Hyperactivity and noncompliance showed rapid and clinically significant improvement at Day 170 compared with Natural History data.
•  Sleep, gross motor function, and behavior assessed by ASA showed rapid and clinically meaningful improvement, exceeding treatment benefit observed in the Dose-escalation Cohorts at Day 170.
•  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). Most 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 showed continuing long-term improvement compared with Natural History data and exceeded the threshold of clinical significance by many-fold in many patients.
•  Behavior and sleep assessed by ASA showed continuing 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 on Day 338. The majority of patients had a total net response of +2 to +4 and a 2- to 5-fold improvement over the MID threshold in several domains.

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.

Price Action: RARE shares are down 9.55% at $42.51 on the last check Monday.