Ultragenyx Pharmaceutical (NASDAQ:RARE) used its fourth-quarter and full-year 2025 earnings call to outline what management described as key upcoming inflection points in 2026, while also detailing a strategic restructuring aimed at aligning spending with late-stage programs and a goal of profitability in 2027.
2025 results and 2026 revenue outlook
Chief Financial Officer Howard Horn said Ultragenyx reported 2025 total revenue of $673 million, up 20% from 2024 and above the upper end of the company’s guidance range. Product contributions included:
- Crysvita: $481 million (17% growth year over year), including $275 million from North America, $177 million from Latin America and Turkey, and $29 million from Europe
- Dojolvi: $96 million (9% growth)
- Evkeeza: $59 million (84% growth, with demand building following launches in territories outside the U.S.)
- Mepsevii: $37 million
For 2026, Horn guided to total revenue of $730 million to $760 million (8% to 13% growth over 2025), excluding potential revenue from new product launches. Crysvita revenue is expected to be $500 million to $520 million, reflecting underlying demand growth but partially offset by expected timing of ordering patterns in Brazil that management anticipates will normalize in 2027. Dojolvi revenue is expected to be $100 million to $110 million.
Restructuring plan and profitability target
Management said it implemented a strategic restructuring plan following the UX111 complete response letter (CRL) last year and results from the UX143 trials. Horn said the plan is intended to refocus headcount and spending on near-term value drivers while reducing internal and external spend across manufacturing, clinical, early-stage research, and general and administrative functions.
As part of the plan, Ultragenyx announced a 10% workforce reduction impacting approximately 130 full-time employees. Horn said the restructuring supports the company’s broader strategy to become profitable in 2027 while continuing to grow its four-product commercial base and investing in three planned launches: UX111, DTX-401, and GTX-102.
On expenses, Horn said Ultragenyx expects 2026 combined R&D and SG&A to be flat to down low single digits versus 2025, after netting restructuring-related severance and one-time costs along with targeted launch investments for UX111 and DTX-401. For 2027, he said R&D expenses are expected to decrease 38% versus 2025, or approximately $280 million, driven by completion of clinical and manufacturing spending on multiple Phase III studies and reduced early-stage research efforts. SG&A is expected to increase in 2027 to support launches and existing products, but on a combined basis R&D and SG&A are expected to decrease at least 15% in 2027 versus 2025.
During Q&A, Horn also discussed dynamics that could affect modeling as products move into launch mode, including reduced R&D expense due to capitalization of manufacturing costs post-approval and higher gross margins from selling inventory previously expensed pre-approval. Management said its financial plan also considers two priority review vouchers (PRVs) tied to anticipated approvals; Horn said the company’s base internal modeling assumes a value just north of $100 million per PRV and that the company would aim to monetize vouchers promptly, though the structure (including potential option agreements) remains to be determined.
Regulatory and clinical catalysts: UX111 and DTX-401
Chief Executive Officer Emil Kakkis said 2026 could be significant, pointing to two potential approvals—UX111 for MPS IIIA (Sanfilippo type A) and DTX-401 for glycogen storage disease type Ia (GSDIa)—as well as a pivotal data readout in Angelman syndrome.
Kakkis highlighted updated long-term UX111 data presented at the World Symposium, saying results showed sustained separation for early-treated patients across multiple neurological endpoints compared to natural history, as well as significant and durable reduction in cerebrospinal fluid (CSF) heparan sulfate and other biomarkers.
However, management said the company received an incomplete response letter (IRL) from the FDA after resubmitting the UX111 BLA late last month. Kakkis said the company had provided complete responses to each CRL item, but the FDA is now requiring additional details within supportive documentation for the chemistry, manufacturing, and controls (CMC) responses and their impact. Kakkis said the information is typically provided during an inspection, and Ultragenyx plans to include it in a new resubmission.
In Q&A, management said the FDA is requesting extensive supportive documentation, such as standard operating procedures and evidence of effectiveness of changes, rather than descriptions of actions taken. Kakkis said Ultragenyx expects a process similar to the prior resubmission timeline once the package is resubmitted, with the FDA taking a couple of weeks to determine whether all documents are included and a PDUFA date being set approximately six months after submission.
Chief Medical Officer Eric Crombez said Ultragenyx completed the rolling BLA submission for DTX-401 at the end of December and expects a PDUFA action date in the third quarter of the year. On commercialization expectations, Kakkis said GSDIa is an urgent disease but suggested uptake may be “strong, steady” rather than immediate all-at-once demand. He also said Ultragenyx has discussed a $1 million to $2 million pricing range for GSDIa and a $2 million to $4 million range for MPS IIIA, while noting pricing for GSDIa has not been set.
Angelman syndrome: endpoint strategy and Phase III data timing
For GTX-102 in Angelman syndrome, Crombez said the company continues treating patients in the 48-week ASPIRE study and enrolling in the supportive AURORA study, with ASPIRE Phase III data expected in the second half of 2026.
Management addressed multiple questions on endpoint selection and trial conduct. Kakkis said the company chose Bayley-4 cognition as the primary endpoint because cognition is foundational and communication can be heterogeneous and slower to develop. He added that the study also allocates power to a Multi-Domain Responder Index covering cognition, receptive communication, sleep, behavior, motor function, and other areas aimed at capturing broader benefits important to families.
Regarding control arm expectations, Kakkis said the company assumes one point or less cognitive change on the Bayley in the natural history and randomized control setting, and described the measure as rigorous and not prone to placebo effects. He said Ultragenyx is using comprehensive site training and, where possible, centralized testers to improve consistency across sites.
On retention, management said the Phase III program has had very few dropouts and a high rate of patients electing to continue in the long-term extension, consistent with prior studies.
Commercial execution and pipeline updates
Chief Commercial Officer Erik Harris said Ultragenyx entered 2026 with a “proven commercial infrastructure,” emphasizing year-over-year consistency across its four marketed products and ongoing geographic expansion. Harris reiterated expectations for variability in Crysvita revenue due to uneven ordering patterns, particularly in Latin America where Brazil’s Ministry of Health places large orders.
Harris also noted Dojolvi’s continued steady growth five years after launch, including more than 100 started forms in the U.S. for the third straight year, and cited regulatory developments such as early marketing authorization in Kuwait (September 2025) and approval of an early access pathway in the U.K. (April 2025). For Japan, Harris said Dojolvi received conditional approval and that the company expects full approval and launch in the second half of 2026.
In other pipeline updates, Crombez said Ultragenyx completed enrollment in the fourth dosing cohort of UX701 for Wilson disease and expects to share data from all four cohorts later in 2026, with management noting timing depends on patient progression and duration of follow-up. Kakkis also said the company’s DTX-301 gene therapy program for ornithine transcarbamylase (OTC) deficiency is ongoing in Phase III, with data from the ammonia endpoint expected this year; he later added the Phase III trial enrolled around 37 patients and is evaluating changes in ammonia versus control as the primary endpoint, with an additional assessment of standard-of-care withdrawal in a second study portion.
About Ultragenyx Pharmaceutical (NASDAQ:RARE)
Ultragenyx Pharmaceutical Inc is a biopharmaceutical company focused on developing and commercializing therapies for rare and ultra-rare genetic disorders. Since its founding in 2010 and headquarters in Novato, California, the company has built expertise in protein replacement therapies, small molecules and gene therapy approaches to address high-unmet medical needs. Ultragenyx applies a precision medicine model, leveraging both in-house research and strategic collaborations to advance its product pipeline from discovery through regulatory approval.
The company’s commercial portfolio includes Crysvita (burosumab-tmyl) for X-linked hypophosphatemia, Mepsevii (vestronidase alfa-vjbk) for mucopolysaccharidosis VII and Dojolvi (triheptanoin) for long-chain fatty acid oxidation disorders.
