Ultragenyx Reports Q4 2025 Results, Resubmits UX111 Gene Therapy Application to FDA

Ultragenyx Pharmaceutical reported fourth-quarter 2025 loss of $1.29 per share, wider than the consensus estimate of a loss of $1.20. Total revenues amounted to $207 million in the reported quarter, up 25% year over year, on the back of higher product sales. The top line beat the consensus estimate of $203 million.

On February 3, Ultragenyx announced positive long-term data for UX111, an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA), demonstrating sustained reductions in cerebrospinal fluid heparan sulfate (CSF-HS) and significant improvements in clinical function. With up to 8.5 years of follow-up, the study showed that treated children achieved a median 63.98% reduction in CSF-HS and exhibited unprecedented separation from natural history data, specifically regarding cognitive, communication, and motor skills.

Younger patients and those with earlier-stage disease showed the most robust treatment effects, while older children retained critical functional abilities, such as verbal communication and independent ambulation, far beyond the typical age of decline seen in untreated peers. The safety profile of UX111 remains favorable and well-tolerated.

Following these encouraging results, Ultragenyx resubmitted its BLA to the US FDA in January 2026, seeking accelerated approval for UX111. The submission includes the latest long-term functional and biomarker data to support the clinical benefit of the gene therapy across various patient ages and disease severities. The company anticipates a review period of up to six months per FDA guidelines, with a PDUFA action date expected in Q3 2026. However, the UX111 BLA resubmission was met with an incomplete response letter, requiring prompt provision of additional CMC documentation prior to FDA review continuation.

Earlier in 2025, Ultragenyx faced a massive setback when the FDA issued a complete response letter (CRL) for its biologics license application (BLA) for UX111.

The company markets four drugs, namely Crysvita, Mepsevii, Dojolvi and Evkeeza. Crysvita is approved for treating X-linked hypophosphatemia, an inherited disorder and tumor-induced osteomalacia, an ultra-rare disease. Mepsevii is approved to treat Mucopolysaccharidosis VII, also known as Sly syndrome. Dojolvi is approved for treating all forms of long-chain fatty acid oxidation disorders. Evkeeza is indicated for homozygous familial hypercholesterolemia (HoFH).

Crysvita's total revenues were $145 million, up 25% year over year, driven by increased demand for approved indications. Crysvita's net product revenues in the fourth quarter of 2025 included $97 million from North America, $40 million from Latin America and Turkey, and $8 million from Europe. Mepsevii product revenues increased 63% year over year to $13 million in the reported quarter. Dojolvi product revenues were $32 million, up 3%, driven by new patient demand. Evkeeza recorded sales of $17 million in the fourth quarter, up 70% as Ultragenyx continues to launch the drug in its territories outside of the United States.

In 2022, Ultragenyx announced a license and collaboration agreement with Regeneron Pharmaceuticals for Evkeeza, which is approved in multiple geographies as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Per the deal, Ultragenyx has obtained the rights to develop, commercialize and distribute Evkeeza outside the United States. The regions include the European Economic Area. However, Regeneron solely commercializes Evkeeza in the United States. Formal reimbursement was achieved in all major EMEA markets, serving approximately 350 patients across 20 countries.

Operating expenses of $321 million in the quarter rose 12% year over year due to increased investments in multiple late-stage pipeline programs and marketing costs for approved drugs. Operating expenses included research and development (R&D) expenses of $203 million (up 8%), selling, general and administrative (SG&A) expenses of $89 million (up 9%), and cost of sales of $29 million (up 71%).

Total revenues in 2025 came in at $673 million, up 20% from $560 million recorded in 2024. The figure missed the consensus estimate of $675 million. The net loss per share in 2025 came in at $5.83, which is narrower than the loss of $6.29 reported in 2024. The reported figure was wider than the consensus estimate of a loss of $5.71 per share. Net cash used in operations in 2025 was $466 million.

Crysvita revenue totaled $481 million in 2025, including $275 million from North America, $177 million from Latin America and Turkey, and $29 million from Europe, representing 17% year-over-year growth. Dojolvi revenue reached $96 million in 2025, showing 9% year-over-year growth. Evkeeza revenue was $59 million in 2025, reflecting 84% year-over-year growth attributed to demand outside the United States. Mepsevii revenue totaled $37 million in 2025, serving patients with an ultra-rare indication. Products were distributed in more than 35 countries in 2025, each contributing to annual revenue.

Ultragenyx expects total revenues in 2026, excluding potential revenues from new product launches, between $730 million and $760 million, which suggests growth of approximately 8-13% compared to 2025. Crysvita revenues in 2026 are expected to be in the range of $500-$520 million, indicating growing underlying global demand partially offset by the expected timing of ordering patterns in Brazil. Dojolvi revenues are expected to be between $100 million and $110 million in 2026.

Ultragenyx reported launching a strategic restructuring plan aimed at cutting costs, reducing headcount, and sharpening its focus on its highest-value programs, as it targets profitability in 2027. The company said the move is intended to streamline operations while supporting revenue growth from existing and upcoming product launches.

As part of the plan, Ultragenyx will reduce its workforce by 10%, affecting about 130 employees. The company expects combined R&D and SG&A expenses in 2026 to be flat to down low-single digits compared with 2025, including roughly $50 million in severance, manufacturing and other one-time restructuring costs.

Looking ahead to 2027, Ultragenyx projects R&D expenses will fall 38% from 2025 levels, or about $280 million, driven by the completion of several phase III studies and a pullback in early-stage research. While SG&A spending is expected to rise to support product launches and commercial efforts, total R&D and SG&A expenses are forecasted to decline at least 15% compared to 2025.

Cash, cash equivalents and marketable debt securities amounted to $737 million as of Dec. 31, 2025, compared with $447 million as of Sept. 30, 2025. In the past six months, shares of Ultragenyx have lost 19% against the industry's 22% growth.

Rolling BLA for DTX401 was completed in December 2025, with a PDUFA action date expected in Q3 2026. Pivotal Angelman syndrome data (GTX102) is expected in 2026. UX701 full cohort data readout is anticipated in 2026. Preparations are underway for launches in UX111, DTX401, and GTX102 within the next two years.

Dojolvi received early marketing authorization in Kuwait and approval of early access in the UK during 2025, along with conditional approval in Japan, with full approval anticipated in 2026.