Jazz Pharmaceuticals (NASDAQ:JAZZ) reported fourth-quarter and full-year 2025 results that management characterized as a “transformational” year, highlighted by record revenue, multiple regulatory milestones, and expanding focus on rare disease as a long-term strategic priority.
Record 2025 revenue and expanding portfolio
Chief Executive Officer Renée Galá said 2025 marked Jazz’s 21st consecutive year of top-line revenue growth. The company delivered record total revenue of $4.3 billion for the full year, including fourth-quarter revenue of $1.2 billion, which increased 10% year over year and represented the company’s highest quarterly revenue to date.
- Modeyso, approved and launched after the April acquisition of Chimerix; the product generated $48 million in 2025 revenue from an August launch.
- Zepzelca approved in October in combination with atezolizumab in the first-line maintenance setting for extensive-stage small cell lung cancer.
- Progress in zanidatamab, with leadership highlighting Phase III data they described as “practice-changing,” supporting broader development across HER2-expressing tumors.
Galá also said Jazz resolved “nearly all major litigation,” including settling outstanding ANDA litigation for Epidiolex, which she said extends the product’s runway into the “very late 2030s.”
Commercial performance: sleep, epilepsy, and oncology
Chief Commercial Officer Sam Pearce detailed 2025 performance across Jazz’s diversified commercial portfolio.
In sleep, the company reported more than $2.0 billion in 2025 revenue across XYWAV, Xyrem, and authorized generic royalties, including $559 million in the fourth quarter. XYWAV revenue grew 12% to approximately $1.7 billion for the year and reached $465 million in the fourth quarter, up 16% year over year. Pearce said the low-sodium profile continues to resonate with patients and physicians, contributing to approximately 500 net patient adds in the fourth quarter and more than 2,000 net patient adds in 2025. She highlighted growth in idiopathic hypersomnia (IH), including a 34% increase in net active IH patients, noting XYWAV is the only FDA-approved treatment for IH.
Epidiolex reached “blockbuster” status with $1.1 billion in 2025 revenue, up 9% year over year, with Pearce citing 7% volume growth. Fourth-quarter revenue was $287 million, up 4%, with management noting a tougher comparison due to higher-than-normal inventory at the end of 2024. Pearce said the company sees growth opportunity in adults, including expanded reach into long-term care settings and greater use of a Nurse Navigator program to improve persistency.
In oncology, Pearce highlighted:
- Ziihera (zanidatamab) as a “key pillar” of future growth, with the largest near-term opportunity described as first-line metastatic gastroesophageal adenocarcinoma (GEA), where Jazz said it has potential to launch in the second half of 2026.
- Modeyso (for H3K27M-mutant diffuse midline glioma) with early uptake largely in academic centers; Pearce said more than 360 patients received Modeyso in 2025. She stated Jazz believes Modeyso represents a U.S. peak sales opportunity of greater than $500 million, while acknowledging ongoing work to understand real-world treatment duration and market dynamics.
- Zepzelca generated $307 million in 2025 revenue, including approximately $90 million in the fourth quarter, up 15% year over year. Pearce said fourth-quarter growth was primarily driven by initial first-line demand and that commercial focus will prioritize the first-line maintenance setting going forward, with expectations for declining second-line use and increased first-line maintenance adoption.
Pipeline updates and regulatory path for zanidatamab
Global Head of R&D and Chief Medical Officer Rob Yannone emphasized the company’s Phase III HORIZON-GEA data and the push toward a first-line metastatic GEA filing. Yannone said the zanidatamab plus tislelizumab and chemotherapy arm showed a statistically significant overall survival (OS) improvement versus trastuzumab control, including “more than seven months” improvement and a 28% reduction in risk of death. He added that benefits were observed in both PD-L1 positive and PD-L1 negative subgroups.
For zanidatamab plus chemotherapy, Yannone said median OS was “over two years,” with a trend toward statistical significance at the first interim analysis. He said an additional planned interim OS analysis is expected mid-year.
On regulatory timing, Yannone said Jazz expects to complete submission of a supplemental Biologics License Application for zanidatamab under Real-Time Oncology Review in the first quarter and added that the FDA granted Breakthrough Designation for zanidatamab in GEA. Based on these factors, management said there is potential to launch zanidatamab in GEA in the second half of the year.
Yannone also discussed the Phase III EMPOWER trial in metastatic HER2-positive breast cancer for patients who progressed on or were intolerant to Enhertu. He said Jazz expects to complete enrollment in the first half of 2027, with top-line data anticipated in late 2027 or early 2028. In Q&A, management described EMPOWER as a 550-patient, two-arm study comparing zanidatamab versus Herceptin, with progression-free survival and an interim overall survival analysis before final OS readout.
Beyond zanidatamab, Yannone said Jazz initiated a Phase I healthy volunteer study of JZP-047 in January to evaluate the compound for absence epilepsy, noting Jazz has not disclosed the mechanism and that it is not a cannabinoid. The company also initiated a Phase I-b trial of Epidiolex in focal onset seizures. Yannone said Jazz decided to stop development of JZP441 and end its partnership with Sumitomo, while continuing work on a backup orexin program.
2026 guidance and evolving sleep dynamics
Chief Financial Officer Phil Johnson reported non-GAAP adjusted net income of approximately $522 million in 2025 and non-GAAP adjusted EPS of $8.38. For 2026, Jazz guided total revenue to $4.25 billion to $4.50 billion, implying about 2.5% growth at the midpoint.
Johnson said the company expects double-digit growth in rare oncology and epilepsy revenue in 2026, driven primarily by Epidiolex, Modeyso, and Ziihera. By contrast, the rare sleep franchise may decline due to the introduction of multiple generic high-sodium oxybate products. Jazz guided total rare sleep revenue to $1.8 billion to $1.9 billion, down modestly from $2.01 billion in 2025, with pressure expected primarily from Xyrem and Hikma authorized generic royalty revenue. Xyrem generated $146 million in 2025 revenue.
For XYWAV specifically, Jazz guided revenue to be flat to up mid-single digits in 2026. Management said it does not anticipate a material impact to low-sodium XYWAV revenue in the first half of 2026 because XYWAV is not AB-rated to high-sodium oxybate, though the company expects competitive dynamics to evolve in the second half of the year as generic volumes build and as wake-promoting agents potentially enter the market. In Q&A, management also addressed the possibility of payer actions such as step edits, while arguing that physician demand for a low-sodium option could support access even if payer policies tighten.
On profitability and spending, Jazz guided to a non-GAAP adjusted gross margin of 90% to 91%, citing higher royalties from products such as Modeyso and Ziihera and noting tariffs as a potential secondary factor. The company guided non-GAAP adjusted SG&A to $1.26 billion to $1.32 billion and non-GAAP adjusted R&D to $725 million to $775 million, with R&D increases driven by expanded zanidatamab studies and other pipeline investments. Johnson said Jazz is not guiding to adjusted net income or EPS in 2026.
Jazz ended 2025 with $2.4 billion in cash and investments and generated approximately $1.4 billion in cash from operations during the year. In Q&A, Johnson said the company ended 2025 at about 1.5 turns net leverage and has the ability to lever up for compelling transactions, while expecting debt to represent a smaller portion of capitalization over time.
About Jazz Pharmaceuticals (NASDAQ:JAZZ)
Jazz Pharmaceuticals plc is a global biopharmaceutical company focused on developing and commercializing therapies in neuroscience and oncology. The company’s research and development efforts target unmet medical needs in sleep disorders, hematologic malignancies, rare neurological conditions and solid tumors. Jazz’s product portfolio includes therapies for narcolepsy, hepatic veno-occlusive disease, acute myeloid leukemia and other serious disorders.
Flagship products from Jazz Pharmaceuticals include Xyrem® (sodium oxybate) and Xywav® (calcium, magnesium, potassium, and sodium oxybates) for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy.
