Ultragenyx Pharmaceutical has begun its pivotal Phase 3 Aspire study evaluating GTX-102, an experimental treatment for Angelman syndrome. The study, which commenced dosing its first patient in December 2024, aims to enroll approximately 120 children aged 4 to 17 who have been genetically diagnosed with a full maternal UBE3A gene deletion, a characteristic of Angelman syndrome.
Aspire Study Design and Endpoints
The Aspire study is designed as a randomized, sham-controlled trial where participants are assigned in a 1:1 ratio to receive either GTX-102 or a sham comparator over a 48-week primary efficacy analysis period. The treatment regimen involves three monthly loading doses of GTX-102 at 8 mg, followed by a maximum of 14 mg quarterly during maintenance. The primary endpoint of the Aspire study is to measure cognitive improvement through the Bayley-4 cognitive raw score. A key secondary endpoint is the Multi-domain Responder Index (MDRI), which assesses five domains: cognition, receptive communication, behavior, gross motor function, and sleep. After the initial 48 weeks, patients who received the sham treatment will be eligible to crossover to GTX-102.
GTX-102: Mechanism and Potential
GTX-102 is being developed as a potential disease-modifying therapy for Angelman syndrome, a rare neurogenetic disorder characterized by developmental delay, intellectual disability, seizures, and movement disorders. The drug aims to address the underlying genetic cause of the condition.
Analyst Outlook and Financial Performance
H.C. Wainwright has maintained its Buy rating and $95.00 price target for Ultragenyx Pharma, indicating significant upside from the current trading price. Analyst consensus remains strongly bullish, with price targets ranging from $48 to $140. Ultragenyx reported a 42% year-over-year increase in Q3 2024 revenue, totaling $139 million. However, the company also recorded a net loss of $134 million for the same quarter. Despite this, analysts maintain a strong buy consensus on the stock.
Broader Pipeline and Future Prospects
In addition to GTX-102, Ultragenyx is seeking FDA approval for its Sanfilippo A gene therapy, UX111. The company is also anticipating an interim analysis from the Phase 3 portion of the Orbit study for setrusumab around the end of 2024 or early 2025. Ultragenyx's CEO, Emil Kakkis, has emphasized the importance of timely execution in rare disease programs and is optimistic about the company's future. The company anticipates reaching GAAP profitability by the end of 2026 and is preparing for Biologics License Application submissions for treatments targeting rare diseases, with potential for three new therapies launching in upcoming years.
