Ultragenyx Pharmaceutical (RARE) TD Cowen 46th Annual Health Care Conference summary

Angelman syndrome program updates

• Aspire phase III study targets cognition as the primary endpoint, with a clinically meaningful difference set at five points and over 90% power for success based on modeling.

• Homogeneous patient population with full deletions was chosen to minimize variability and placebo effect, excluding caregiver input in assessments.

• Aurora study uses a basket approach to include broader genotypes and age ranges, aiming to support a broader label through extrapolation of safety and efficacy.

• Both cognition and MDRI are considered primary endpoints, tested in parallel, with domain-specific meaningful score differences negotiated with the FDA.

• Aurora is about 6–12 months behind Aspire in enrollment and progress.

Setrusumab and bone disease strategy

• Statistically significant improvements in bone mineral density and vertebral fractures observed, with vertebral fractures validated as a key clinical endpoint.

• Accelerated approval pathway is being considered, supported by clinical benefit and biomarker validation, with a confirmatory study planned.

• Confirmatory study may focus on pain or fracture endpoints, likely to be larger and longer-term, with crossover extension considered helpful.

• Accelerated approval is not expected to impact pricing or value, especially in rare diseases.

• Label differentiation may rely on bone mineral density and vertebral fracture data.

Gene therapy and regulatory interactions

• FDA feedback for Sanfilippo syndrome gene therapy focused on clinical data, with current delays due to manufacturing SOP documentation rather than new clinical data.

• Resubmission after addressing SOPs will trigger a two-week validation and up to six-month review period.

• Manufacturing for GSDIa is now in-house at Bedford, with validation period cleared and PDUFA date set.

• SOP updates for GSDIa and other products can be done in parallel, with a phased approach to bringing manufacturing in-house.