Ultragenyx's Q2 2025 Earnings Call: Dissecting Contradictions on Setrusumab Efficacy, FDA Interactions, and Resubmission Strategy

Setrusumab efficacy and study power, FDA interactions and impact on rare disease development, setrusumab study timeline and interims, setrusumab study design and powering, UX111 resubmission strategy are the key contradictions discussed in Ultragenyx Pharmaceutical's latest 2025Q2 earnings call.



Orthopedic Program Progress:
- For UX143, setrusumab for osteogenesis imperfecta, the Orbit and Cosmic studies are continuing to the final analysis, expected to occur around the end of the year.
- The DMC recommended continuing to the final analysis due to a positive safety profile and a 50% improvement threshold for fracture rates.
- Progress is based on the known benefits of UX143 in building bone and reducing excess resorption, which increases bone strength and reduces fractures, enhancing overall bone health.

Angelman Syndrome Clinical Trial Enrollment:
- The Phase III Aspire study for GTX-102 completed enrollment ahead of plan with 129 patients in 7 months.
- Enrollment was driven by rapid interest from investigators and patient communities, reflecting the urgent need for a treatment.
- This rapid enrollment underscores the strong desire for an effective treatment and is supported by encouraging data from Phase I/II studies, leading to its Breakthrough Therapy designation.

Commercial Performance:
- Total revenue for the first half of 2025 was $306 million, representing 20% growth over the prior year, on track to deliver $640 million to $670 million for the year.
- Crysvita continues to grow in line with expectations, contributing significantly to revenue with $120 million in the second quarter.
- The growth in Crysvita sales is driven by successful negotiations with Brazilian and Mexican authorities, as well as expansion in other Central and South American countries.

Regulatory Interactions and Pipeline:
- Ultragenyx received a Breakthrough Therapy designation for GTX-102, indicating the FDA's recognition of its significant potential in treating Angelman syndrome.
- The company is working with the FDA to address observations from the UX111 CRL, with plans to resubmit the BLA following agreement on a resolution plan.
- The focus remains on maintaining GAAP profitability by 2027, with strategic expense management and the anticipation of PRV proceeds from approved products.