Ultragenyx to Slash Costs After Setrusumab Phase 3 Fracture Trial Failure, BMD Gains
Ultragenyx reported that its Phase 3 Orbit and Cosmic trials of setrusumab in osteogenesis imperfecta failed to meet primary endpoints on fracture rate, though both showed statistically significant improvements in bone mineral density. Company to cut expenses, targets two gene therapy launches and Phase 3 Angelman syndrome data in 2026.
1. Analyst Maintains Optimistic Outlook Despite Recent Sell-Off
Following a more than 42% decline in Ultragenyx Pharmaceutical shares after Phase 3 setbacks for setrusumab, Wells Fargo analyst Benjamin Burnett reiterated an overweight rating on the stock and reduced his price target from $65 to $45. With the stock closing at $19.72 yesterday, his target suggests more than 128% upside. Burnett cited a favorable risk-reward profile based on statistically significant improvements in bone mineral density and urged investors that “it’s too soon to throw in the towel” as the company awaits FDA feedback on setrusumab’s secondary endpoint successes.
2. Phase 3 Orbit and Cosmic Studies Miss Primary Endpoints but Achieve Secondary Goals
Ultragenyx’s pivotal Phase 3 Orbit study (159 patients across 11 countries) and the pediatric Cosmic trial (69 patients across 7 countries) for setrusumab failed to meet their primary endpoints of reducing annualized clinical fracture rates versus placebo or bisphosphonates. However, both trials demonstrated statistically significant gains in bone mineral density consistent with earlier Phase 2 results. The low fracture rate in the Orbit placebo arm and the high baseline fracture rate in the younger Cosmic cohort contributed to the outcome. Management has initiated deeper analyses to explore alternative bone-health and clinical endpoints.
3. Rolling Submission of DTX401 BLA Completed with Robust Clinical Data
On December 30, 2025, Ultragenyx announced completion of the rolling Biologics License Application submission for DTX401 (pariglasgene brecaparvovec), its AAV8 gene therapy for Glycogen Storage Disease Type Ia. The application is underpinned by a clinical program involving 52 treated patients and up to six years of follow-up, including Phase 3 GlucoGene data showing significant reductions in daily cornstarch intake, sustained euglycemia, improved fasting tolerance and meaningful gains on the Patient Global Impression of Change scale. DTX401 carries Rare Pediatric Disease, orphan drug, Fast Track and RMAT designations from the FDA, as well as orphan and PRIME designations from the European Medicines Agency.
4. Strategic Expense Reductions and Revenue Diversification
In light of the setrusumab trial outcomes, Ultragenyx announced significant expense reduction measures to preserve runway. The company continues to generate revenue from four approved products and is preparing for near-term gene therapy launches, including DTX401 and another pivotal gene therapy expected to read out in Angelman syndrome. Management emphasizes a time- and cost-efficient development strategy to extend cash resources while advancing a diversified pipeline of rare-disease candidates.