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DATE
May 5, 2026 at 4:30 p.m. ET
CALL PARTICIPANTS
- President and Chief Executive Officer — Renée Galá
- Chief Commercial Officer — Samantha Pearce
- Chief Financial Officer — Philip L. Johnson
- Global Head of R&D and Chief Medical Officer — Robert Iannone
- Head of Investor Relations — John Bluth
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TAKEAWAYS
- Total Revenue -- $1.1 billion, representing more than 19% year-over-year growth, driven primarily by Xywav, Epidiolex, Midevo, and Zepzelca.
- Xywav Net Sales -- $408 million, up 18% year over year, supported by approximately 425 net new patient adds, with the total treated base reaching about 16,600 patients, and inclusion of both narcolepsy and idiopathic hypersomnia indications.
- Epidiolex Net Sales -- $250 million, showing 15% growth, with underlying volume growth of 16%, and heightened focus on expansion into adult and long-term care settings; ex-U.S. growth was primarily driven by volume and favorable foreign exchange.
- Midevo Net Sales -- $41 million since launch in August 2025, with approximately 500 patients treated, exceeding initial duration of treatment expectations, and supporting confidence in the $500 million U.S. peak opportunity assumption.
- Zepzelca Net Sales -- $101 million, increasing 60% year over year, mainly from rapid uptake in the newly approved first-line maintenance setting in combination with Tecentriq.
- ZYHERA (zanidatumab) Oncology Sales -- $13 million, reflecting expanded adoption in biliary tract cancer (BTC), and launch readiness for gastric and esophageal adenocarcinoma (GEA) subjects to pending FDA approval with a PDUFA date of August 25, 2026.
- Cash Flow from Operations -- $408 million, indicating robust cash generation for the quarter.
- Non-GAAP Adjusted EPS -- $6.34 for the quarter.
- SG&A and R&D Dynamics -- Non-GAAP adjusted SG&A expense decreased by $164 million, reflecting the absence of last year's $172 million litigation settlement; adjusted R&D increased by $13 million due to Midevo clinical and compensation costs.
- FDA and Regulatory Pipeline -- ZYHERA's sBLA for first-line HER2-positive GEA accepted under priority review (PDUFA: August 25, 2026), with launch preparation underway; ongoing multiple zanidatumab registrational trials and second interim readout for the Horizon GEA trial expected midyear.
- 2026 Financial Guidance -- Total revenue guidance reaffirmed at $4.25 billion to $4.5 billion, with company assumptions including second-half competitive pressure in sleep (high-sodium generics and new agents), and declining Xyrem and authorized generic revenues.
- Balance Sheet -- Company ended the quarter with $2.9 billion in cash and investments, underscoring continued investment flexibility for business development, and R&D opportunities.
SUMMARY
Jazz Pharmaceuticals (JAZZ +2.02%) delivered its highest-ever first quarter revenue, with every promoted brand posting double-digit growth and significant commercial momentum sustained across sleep, epilepsy, and oncology franchises. Management outlined clear expectations for the anticipated U.S. launch of ZYHERA (zanidatumab) in first-line HER2-positive GEA before or by the August 25, 2026 PDUFA date, bolstered by Horizon trial results showing median overall survival of 26.4 months for the triplet arm. The company highlighted strong operational cash generation and reaffirmed 2026 total revenue guidance, while indicating continued strategic business development activity and disciplined capital allocation. Cash reserves and operational performance are positioned to fund portfolio and pipeline expansion, with regulatory and clinical trial catalysts expected before year-end.
- Renée Galá stated, We are ready to launch ZYHERA in GEA as soon as we receive FDA approval, and we expect ZYHERA will become the HER2-targeted therapy of choice for HER2-positive first-line GEA patients given the magnitude of benefits seen across both experimental arms when compared to the trastuzumab control arm.
- Samantha Pearce confirmed ongoing efforts to maximize Epidiolex persistency and adult market expansion, supported by targeted physician education, and dedicated field teams.
- R&D leadership emphasized the breadth of pipeline progress, with a pivotal Phase III trial in post-ENHERTU metastatic breast cancer for zanidatumab enrolling, and a confirmatory first-line Midevo trial progressing toward 2026/2027 data readout.
- Management highlighted recent additions to the Orange Book-listed patent estate, with new Zepzelca patents extending protection to 2040, and ongoing litigation providing up to a 30-month stay on ANDA approvals from five filers.
INDUSTRY GLOSSARY
- Biparatopic Binding: Mechanism by which a therapeutic antibody (such as zanidatumab) binds two distinct epitopes on the same antigen (HER2), enabling enhanced receptor clustering and immune activation distinct from traditional monoclonal antibodies.
- PDUFA Date: Prescription Drug User Fee Act-mandated deadline by which the FDA must complete review of a new drug application or supplemental application; for ZYHERA, set for August 25, 2026.
- JazzCares: Jazz Pharmaceuticals' proprietary suite of patient support services, including nurse navigation and educational services, designed to improve treatment initiation, adherence, and persistency.
- J-code: Permanent reimbursement code for drugs, which can simplify and expedite payer coverage and physician reimbursement in the U.S.; ZYHERA’s J-code was obtained through BTC approval.
- VPAG: Voluntary Pricing and Access Agreement in the United Kingdom, referenced in context of ex-U.S. Epidiolex pricing adjustments impacting net sales performance.
- Rest-LGS Tool: Diagnostic instrument to aid in identifying Lennox-Gastaut syndrome, supporting market penetration for Epidiolex among adult epilepsy patients.
- AMPHORA Study: Clinical trial evaluating Zepzelca in combination with Tecentriq for first-line maintenance treatment in extensive-stage small cell lung cancer.
- ANDA Filer: Company submitting an Abbreviated New Drug Application to gain FDA approval for a generic version of a branded drug, triggering potential patent litigation and regulatory review timelines.
- Horizon GEA Trial: Registrational study evaluating zanidatumab (ZYHERA) in patients with HER2-positive, first-line, locally advanced or metastatic gastric and esophageal adenocarcinoma; pivotal for FDA review and future commercial adoption.
Full Conference Call Transcript
Operator: Good day, and thank you for standing by. Welcome to the Jazz Pharmaceuticals plc 2026 first quarter earnings conference call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, John Bluth, Head of Investor Relations. Please go ahead. Thank you, and good afternoon, everyone.
John Bluth: Today, Jazz Pharmaceuticals plc reported its first quarter 2026 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website along with the press release and quarterly report on Form 10-Q for the first quarter ended 03/31/2026. On the call today are Renée Galá, President and Chief Executive Officer, Samantha Pearce, Chief Commercial Officer, Robert Iannone, Global Head of R&D and Chief Medical Officer, and Philip L. Johnson, Chief Financial Officer.
On slide two, I would like to remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, growth potential, and anticipated development, regulatory and commercial milestones, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements. We encourage you to review these risks and uncertainties described in today's press release and under the caption Risk Factors in our annual report on Form 10-K for the fiscal year ended 12/31/2025. We undertake no duty or obligation to update our forward-looking statements. As noted on slide three, we will discuss non-GAAP financial measures on this webcast.
Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website. I will now turn the call over to Renée.
Renée Galá: Thanks, John. Good afternoon, everyone, and thank you for joining today's conference call, led by commercial execution across our highly differentiated products for sleep, epilepsies, and cancers. This resulted in our highest-ever first quarter total revenues of $1.1 billion, reflecting more than 19% year-over-year growth driven by the outstanding performance of Xywav, Epidiolex, Midevo, and Zepzelca. Our commercial teams generated double-digit growth across all our promoted brands, and saw strong contributions from our ongoing launches. This performance reflects the disciplined and consistent efforts of our team, working with clarity and purpose to support the physicians and patients we serve.
In addition to our impressive commercial performance to start the year, we are urgently advancing the development of zanidatumab for patients with HER2-positive first-line locally advanced or metastatic GEA where the unmet medical need remains significant. The FDA recently accepted our sBLA for ZYHERA under Real-Time Oncology Review, and granted priority review with a PDUFA date of 08/25/2026. We are ready to launch ZYHERA in GEA as soon as we receive FDA approval, and we expect ZYHERA will become the HER2-targeted therapy of choice for HER2-positive first-line GEA patients given the magnitude of benefits seen across both experimental arms when compared to the trastuzumab control arm.
In R&D, we continue to make progress across our pipeline, with multiple ongoing registrational zanidatumab trials, early-stage trials evaluating oncology assets, and the early development of neuroscience and epilepsy assets. The year is also off to an excellent operational start with cash flow of over $400 million in the first quarter, and non-GAAP adjusted EPS of $6.34. Our financial strength and disciplined capital allocation enable us to invest in the continued growth of our commercial portfolio and pipeline, while also positioning us to execute on business development opportunities that fit our strategic focus in rare disease. With that, I will turn the call over to Sam to share more details on commercial performance.
Samantha Pearce: Thank you, Renée. Our commercial team delivered strong results across Jazz Pharmaceuticals plc's portfolio, with momentum from our 2025 launches and coordinated execution continuing into 2026. I will begin on slide seven with sleep. Xywav's net product sales increased 18% to $408 million in 2026, compared to the same period in 2025. As expected, HCPs and patients continue to drive demand for safer, low-sodium Xywav. And we saw strong new patient growth with approximately 425 net patient adds. There are now approximately 16,600 patients taking Xywav, which remains the number one branded treatment for narcolepsy based on product revenues and the only FDA-approved treatment for idiopathic hypersomnia.
Our field teams continue to expand both the IH and narcolepsy markets by educating HCPs on the importance of addressing the full spectrum of daytime and nighttime symptoms. These efforts are complemented by digital and media campaigns to increase disease awareness and support patient education. Our JazzCares support services, including field-based nurse educators, support patients from initiation, through titration, and across the long-term treatment journey. These services remain important differentiators for Jazz Pharmaceuticals plc. Moving to slide eight and Epidiolex. Epidiolex net product sales increased 15% to $250 million in 2026, driven by strong underlying demand and 16% volume growth during the quarter.
Expanding our reach in the adult patient population, and specifically in the long-term care setting remains a key focus and an important near-term growth opportunity. Our nurse navigator program continues to have a meaningful impact on improving patient persistency, and expanding utilization of this resource remains a priority for 2026. Finally, as part of our commitment to bring Epidiolex to appropriate patients in Japan, we have partnered with Nippon Zoki, a Japanese company with deep expertise in CNS disorders. Jazz Pharmaceuticals plc remains the sponsor of the clinical trial, and Nippon Zoki will lead regulatory, distribution, and commercial activities in Japan. Turning to our oncology portfolio, starting with ZYHERA on slide nine.
In 2026, ZYHERA generated net product sales of $13 million. Feedback from biliary tract cancer physicians continues to be positive with real-world experience consistent with the clinical profile observed in our trial. We are also continuing to expand into new community-based accounts beyond academic centers, increasing awareness of ZYHERA in BTC, and building readiness ahead of a potential launch in GEA. As a reminder, there is a substantial customer overlap across our solid tumor footprint, including approximately 90% overlap between BTC and GEA accounts. We believe this positions us well to accelerate uptake in GEA following its anticipated approval and launch on or before the August 25 PDUFA date.
Once approved, our existing cross-functional team will be positioned to reach target customers and support rapid adoption of this practice-changing regimen for GEA patients. Turning to slide 10 and our GEA launch preparations. Physicians are expressing excitement and interest in the potential use of ZYHERA in GEA. It has been more than fifteen years since a new first-line HER2-targeted agent became available for patients with metastatic gastric cancer. Given the unprecedented median overall survival data, of more than two years, we believe ZYHERA has the potential to become the preferred HER2-directed therapy and foundational backbone for treating HER2-positive first-line metastatic GEA.
The addition of tislelizumab further improved survival outcomes in both PD-L1 positive and PD-L1 negative patients, consistent with ZYHERA's unique mechanism of action that generates an innate immune response in the tumor. ZYHERA already benefits from an established permanent J-code through its FDA approval in second-line HER2-positive BTC, which we expect will simplify reimbursement in GEA and reduce the administrative burden for providers. In addition, the compelling outcomes from the Horizon GEA trial support our expectations for favorable payer access. Finally, our comprehensive JazzCares support services, together with ZYHERA's established availability across customers' preferred distribution channels, position us to enable seamless patient access at launch. Turning to slide 11 and Midevo.
Midevo generated $41 million in net product sales in 2026. This strong early performance following its launch in August 2025 reflects the significant unmet need in H3K27M mutant diffuse midline glioma, high awareness driven by advocacy groups, and the value physicians see for patients. Approximately 500 patients have been treated with Midevo since launch through the end of the first quarter. Our highly experienced neuro-oncology field teams, including medical and access colleagues, continue to support the launch. The teams remain focused on expanding reach in community settings, whilst maintaining a well-supported presence in academic centers of excellence. Robust patient-centric support services and payer coverage continue to underpin launch momentum and support appropriate access for patients.
Moving to slide twelve and Zepzelca. In 2026, Zepzelca net product sales increased 60% to $101 million compared to the same period in 2025. Growth in the first quarter was primarily driven by strong uptake in the frontline maintenance setting, following FDA approval of Zepzelca in combination with Tecentriq in October. Given the strength of the AMPHORA clinical data and the opportunity to improve both progression-free survival and overall survival for patients with extensive-stage small cell lung cancer, health care providers are rapidly adopting the Zepzelca combination in the first-line maintenance setting. As a result, this new indication is driving the product's strong performance.
Our commercial initiatives will continue to be focused on first-line maintenance, reflecting our ongoing commitment to this priority. For the rest of 2026, first-line maintenance adoption is expected to grow, with second-line use decreasing due to competition and fewer Zepzelca-naive patients available for treatment. Overall, we are satisfied with the impressive commercial performance achieved across our portfolio in the first quarter and remain focused on maintaining this momentum throughout the year. With that, I will now turn the call over to Rob to provide an update on our pipeline.
Robert Iannone: Thanks, Sam. I will start on slide 14. This is an exciting time at Jazz. In addition to our outstanding commercial execution, we are also preparing to bring zanidatumab to HER2-positive first-line metastatic GEA patients. The data from the Horizon GEA trial definitively demonstrated that zanidatumab offers improved outcomes on all efficacy measures compared to trastuzumab, and should be the new HER2-targeted agent of choice. The data also showed tislelizumab further improved survival outcomes in both PD-L1 positive and PD-L1 negative patients. The benefit regardless of PD-L1 status may be driven by zanidatumab's unique mechanism of action, known as biparatopic binding.
This enables zanidatumab to cross-link neighboring HER2 receptors, leading to receptor clustering which blocks HER2 growth signaling and also triggers the complement cascade. Zanidatumab's ability to uniquely and broadly activate the innate immune system may in part explain the additional efficacy observed when tislelizumab was added to zanidatumab, even in PD-L1 negative tumors. The triplet arm of zanidatumab, tislelizumab, and chemotherapy demonstrated improved overall survival, with a remarkable median OS of 26.4 months, representing a meaningful improvement of more than six months median OS compared to prior studies in HER2-positive patients who have a poor prognosis in the metastatic setting. Among patients who had an objective response, the median duration of response was 20.7 months.
Again, this benefit was observed irrespective of tumor PD-L1 status. To put this into context, in the KEYNOTE-811 trial, the duration of response for trastuzumab and pembrolizumab plus chemotherapy was 11.3 months. We are moving quickly to bring zanidatumab to HER2-positive first-line metastatic GEA patients. Following the oral presentation at ASCO GI in January, we submitted the data for potential inclusion in NCCN guidelines. We are pleased that the manuscript has been accepted for publication by a top-tier medical journal and plan to submit the peer-reviewed manuscript to NCCN once it has been published. Our supplemental BLA for zanidatumab has received priority review, with a PDUFA date of 08/25/2026.
We are actively engaged with the FDA in the review process, and we expect potential approval and launch of zanidatumab in GEA on or before the PDUFA date. Turning to slide 15 and our pipeline. We have multiple clinical trials across our pipeline from early-stage to registrational trials. We look forward to sharing data from some of these ongoing trials at the upcoming ASCO presentations on lurbinectedin and zanidatumab. The second planned interim analysis for overall survival of the zanidatumab and chemotherapy arm of the Horizon GEA trial is still expected midyear. At the time of top-line readout, this arm showed a clinically meaningful effect on overall survival with a strong trend towards statistical significance compared to the control arm.
The next pivotal Phase III trial for zanidatumab is in metastatic breast cancer patients who have progressed on or are intolerant to ENHERTU. Trial enrollment is progressing well. We continue to expect to complete enrollment in the EMPOWUR trial in 2027, with top-line data anticipated in late 2027 or early 2028. Other earlier-stage trials continue to progress across new indications, including a potentially registrational pan-tumor basket trial and a neoadjuvant/adjuvant breast cancer trial. Looking ahead to later this year or early 2027, we anticipate the ongoing Phase III ACTION trial will have an interim overall survival readout.
This trial is designed to confirm the benefit of Midevo and support regulatory approval as frontline therapy directly following radiation instead of waiting for signs of tumor progression before treating with Midevo. We are working with dedicated focus to both realize the full potential of our near-term opportunities and to rapidly progress our pipeline. Our in-house research and development efforts are underway, and we look forward to sharing updates on those and further pipeline progress in the future. Now I will turn the call over to Phil for a financial update.
Philip L. Johnson: Thanks, Rob. I will start with high-level comments on our non-GAAP adjusted P&L as shown on slide 17. Please note that our full financial results are available in today's press release and 10-Q. The outstanding execution of our field-based teams was reflected in record first quarter revenue of $1.07 billion, driven by 45% growth in our oncology portfolio, 18% growth in Xywav, and 15% growth in Epidiolex. Strong underlying performance drove the vast majority of our revenue growth. I do want to point out two smaller items that also contributed to growth this quarter. First, we had the normal thirteen shipping weeks for our U.S. oncology products this quarter; last year's quarter had twelve shipping weeks.
This contributed about two percentage points to our worldwide revenue growth rate. Second, the significant devaluation of the U.S. Dollar led foreign exchange to contribute about one and a half percentage points to our worldwide revenue growth. Moving down the P&L, our non-GAAP adjusted gross margin declined slightly year-on-year, primarily due to higher sales of products carrying royalties, namely Zepzelca and Midevo. Non-GAAP adjusted SG&A expense decreased about $164 million. You may recall that in last year's quarter, we recognized litigation settlement expenses of $172 million. Excluding these expenses, SG&A increased by $8 million driven by the inclusion of Midevo expenses.
Non-GAAP adjusted R&D expenses increased by $13 million primarily due to the inclusion of Midevo clinical trial expenses and higher compensation-related expenses. Non-GAAP adjusted effective tax rate this quarter was slightly lower than our full-year 2026 guidance due to excess tax benefits from share-based compensation, while our shares outstanding for the quarter reflect the accounting effect of our higher share price on our convertible notes and employee stock plans. At the bottom line, we posted very robust non-GAAP adjusted EPS of $6.34. Supported by our strong start to the year, we are reaffirming our full-year 2026 revenue and expense guidance, including total revenue guidance of $4.25 billion to $4.5 billion.
Total revenue guidance for 2026 includes the assumptions you see on slide 18. As a reminder, we assume competitive dynamics in our sleep business will increase in the second half of the year, including high-sodium generics gaining volume, and one or more daytime wake-promoting agents potentially entering the narcolepsy market. We also expect to see a decline in the Xyrem and high-sodium authorized generic revenues as generic high-sodium oxybates build their volumes over the course of 2026. And as Sam mentioned earlier, we expect a decline in second-line use of Zepzelca. Our Q1 performance and focus on disciplined capital allocation position us well to achieve our 2026 guidance. Moving to slide 19, our balance sheet remains strong.
We continue to generate significant cash from our business, recording $408 million of cash from operations in the first quarter of the year. And we ended the first quarter with $2.9 billion in cash and investments. Our overall financial position and robust operating cash flow provide significant flexibility to invest in value-driving commercial and R&D programs as well as in promising corporate development opportunities to support our rare disease strategy. I will now turn the call back to Renée for closing remarks.
Renée Galá: Thank you, Phil. I will conclude our prepared remarks on slide 21. 2026 builds on the successes we achieved in 2025. Our focused commercial execution led to more than 19% growth in the first quarter, and based on these results, we are on track to achieve our 2026 financial guidance. We look forward to several upcoming catalysts, including the second interim of overall survival from the Horizon GEA trial midyear. Top-line readout for overall survival for the confirmatory ACTION trial for Midevo is expected at the end of this year or early next year. And the top-line readout from the trial evaluating zanidatumab in late-stage breast cancer post-ENHERTU treatment is expected in late 2027 or early 2028.
We continue to build upon our proven scientific expertise and capabilities to make a meaningful impact for patients. Supported by our strong financial position, you should expect to see us invest in our commercial brands and pipeline and business development to broaden our portfolio in key strategic focus areas of sleep, epilepsy, and oncology, in addition to other areas of rare disease. I would like to thank all our Jazz Pharmaceuticals plc colleagues for their efforts and dedication to making a difference in the patients' lives that led to an exceptional first quarter. We are relentlessly focused on continuing to deliver life-changing medicines to patients. That concludes our prepared remarks.
I would now like to turn the call over to the operator to open the line for Q&A.
Operator: Thank you. Wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. Our first question today will be coming from the line of Jessica Macomber Fye of JPMorgan. Please go ahead.
Operator: Please go ahead.
Jessica Macomber Fye: Hey, guys. Good afternoon. Thanks for taking my question. Question on zanidatumab for breast cancer. So if we assume zanidatumab beats Herceptin in breast cancer and gets approved one day for use in the post-ENHERTU setting, how do you expect physicians to make decisions about how to sequence agents in the context of a lack of data for other products post-ENHERTU, among other things? Thank you.
Robert Iannone: I am happy to address that, Jess. We became very interested in this space based on good advice from many key experts in the field. And the fundamental issue is that once ENHERTU moves to frontline, there is very little data about which HER2 agent to select as subsequent therapy. So the trial that we are running, 303, will be the first time that we definitively, in a randomized setting, evaluate zanidatumab versus what would be considered a standard of care. So we expect to be out ahead with important data that will inform decisions about whether to use zanidatumab or other HER2 agents in that space.
Operator: Thank you. One moment for the next question. And the next question is coming from the line of Joseph John-Charles Thome of TD Cowen. Your line is open.
Joseph John-Charles Thome: Hi there. Good afternoon. Congrats on the quarter, and thank you for taking my question. Maybe one on Midevo. Do you have any updated thoughts on sort of the size of this patient population? I think historically, it was thought that it was maybe 2,000 or 3,000, but it sounds like you are already hitting, you know, 500 patients. So any thoughts on that total opportunity just given the strength of that launch? And maybe a follow-up, if I can, on M&A. What is your latest thinking in terms of where you would like to go? Obviously, we have seen a lot of activity in the past few weeks in different areas.
What is the sweet spot in terms of size and area of focus for Jazz Pharmaceuticals plc moving forward? Thank you.
Samantha Pearce: Sam here. I am happy to take the one on Midevo to start with. Yes, extremely pleased with the launch so far. $41 million in Q1 really gives us a lot of confidence around achieving that $500 million peak opportunity in the U.S. And as you mentioned, we have had 500 patients treated since launch. I think that just reflects the very high unmet need that we see in this space. Overall survival from diagnosis is just one year. So this product has had a meaningful impact, and it is supported by high awareness from physicians and obviously very strong patient advocacy support as well.
In terms of the size of the patient population, I think our best estimates are aligned to what you mentioned there, and over time, of course, we will continue to evaluate that. But we do see potential upside in duration of treatment, as well as the size of the population. What we have seen so far is that patients are staying on treatment for longer than we initially anticipated. We will have to wait for this cohort of patients to really mature before we get a really good handle on whether the duration of treatment exceeds that we saw in the trial, which is around about ten months. But we are extremely happy with the start.
I think our teams have done an excellent job really executing this launch well in such an important area of medical need.
Renée Galá: And, Joe, this is Renée. I will jump in on BD. We are highly engaged on the BD front, and I do expect us to have deals announced over the course of this year. We do have a clear strategy that is focused on expanding our presence in rare disease. In particular, we believe there is a significant unmet need, so strengthening our current areas of epilepsy, sleep, and rare oncology, also expanding into new areas of rare disease—areas we think we can leverage our capabilities and our footprint to continue to scale our business while driving further growth and profitability.
In terms of the deal types, it really depends on the transaction at hand, but we are looking at licensing, structured deals, also outright M&A. I think the key here to being successful in BD is valuing or de-risking in ways that others do not see and then staying myopically focused on execution, as we did with the Chimerix acquisition and subsequent Midevo launch. We have very strong momentum now with the new Chief Business Officer on board as of January 1. Importantly, we are well positioned to execute. Phil mentioned we have a strong financial position: $2.9 billion in cash and cash equivalents on the balance sheet, strong cash flow.
And while M&A has picked up, we do believe there is still a lot of substrate that is actionable and well aligned with our strategic priorities.
Operator: Thank you. One moment for the next question. Our next question will be coming from the line of Leonid Timashev of RBC. Please go ahead.
Leonid Timashev: I wanted to stay with—you mentioned epilepsy—just wanted to touch on that. You have been making a lot of investments in that area, both with Epidiolex, with the Cenobamate asset, you also have JZP-47 and now you mentioned potentially looking at BD there as well. So I guess just curious how you are thinking about that area, to what extent a continued focus, and how you are thinking about either synergies or risk of cannibalization across so many different assets there? Thanks.
Renée Galá: Yes. Thanks for the question. This is Renée. I would say this is definitely an area of focus for us. There continues to be significant unmet need across the epilepsy space. You see a strong amount of polypharmacy here with respect to multiple medications generally on board, in particular when we are looking at serious refractory epilepsies. We think with the position that we have with Epidiolex being the number one branded product and having very long durability out to the very late 2030s, it gives us greater opportunity to continue to build around that franchise, to build scale.
I am thrilled to see additional opportunities for patients with the strong data that we have been seeing come out with a number of companies, whether that is on the proof-of-concept side starting to go into registrational studies or work that is happening early in pipelines. As we think about ourselves, we think there is plenty of room and unmet need for patients to continue to see new mechanisms explored and new options. So we do think there is still plenty of substrate and a great opportunity for us as a leader in epilepsy.
You will note last quarter, we said we were advancing the first molecule coming out of our labs that was not just a formulation play, but an innovative target, novel mechanism coming out of our lab that went into patients in the epilepsy space. We will continue to invest here, and we are excited about the opportunities.
Operator: Thank you. One moment for the next question. Our next question is coming from the line of Annabel Samimy of Stifel. Your line is open.
Annabel Samimy: Hi, thanks for taking my question. Just want to circle up on Midevo again. Obviously, it has been exceedingly promising since the outset, and you have potential to move into first-line treatment. I guess my question is how should we think about the potential move into first-line treatment? Does it significantly expand the market? Should we think about this like we think about Zepzelca moving into first line and how it significantly inflected growth? I am trying to understand the magnitude given that most patients who are in first line progress to second line. Is it only about duration, or is there a population opportunity there?
Samantha Pearce: Yes. Hi, Annabel. I am happy to take that. Yes, I think there are two factors when we consider the ACTION study and what that will do for Midevo and for patients. Some patients do not make it to second line. So, of course, there are more patients available to be treated. But having the opportunity to get Midevo to patients before they progress will mean that the duration of treatment should be longer if they can use it straight after radiation. So those two things, I think, will contribute to the $500 million peak potential, which does incorporate an assumption that we will have that first-line label. Rob, anything more to add on that?
Robert Iannone: I mean, you covered it well. I would just point out that sometimes it is hard to judge progression in these patients. And then, as you point out, once it is clinically apparent in addition to imaging, the patients may rapidly progress and not benefit from second-line therapy. So the opportunity to start Midevo right after the radiation therapy really does potentially add a significant benefit to patients and ultimately duration of therapy.
Operator: Thank you. One moment for the next question. And our next question is coming from the line of Marc Goodman of Leerink. Please go ahead.
Marc Goodman: Sam, can you talk about Epidiolex OUS? I heard Phil talk about the FX impact, but those numbers could not have just been FX. Something is doing pretty well there. So maybe just talk—was there any particular country? Was there any buy-in? Anything unusual there? And maybe you could just comment on Rylaze as well, which happened to have a really good quarter, and what was happening there. Thanks.
Samantha Pearce: Yes. Thanks for the question, Marc. Yes, it is great to see the performance outside of the U.S. for Epidiolex. Very strong growth indeed. Around about two thirds of that, I believe, was volume, and there was about a third due to FX and some gross-to-net benefits from places like the U.K. with a VPAG adjustment that happened there. I think this is just down to terrific execution by our teams. As you know, Epidiolex was launched a little bit later in Europe, so there is still quite some opportunity to continue to penetrate in the pediatric segment, but, of course, also in that adult segment, which is a focus for both U.S. and the ex-U.S. business.
And then your other question around Rylaze, yes? Rylaze delivered a strong quarter, $100 million, which was 10% revenue growth. But that was comparing to quite a low Q1 2025. So I think the performance that we have seen in this quarter is in line with the prior quarters that we have seen, other than the Q1 which is a low point. What we have seen with Rylaze is the COG impact that started in 2024 has been fully realized now. Our focus continues to be on making sure that appropriate patients can receive Rylaze, that they are switched at the first sign of a hypersensitivity reaction, and the opportunity to continue growth in AYA.
But I think that $100 million per quarter for Rylaze is a good kind of stable base for us currently.
Operator: Thank you. One moment for the next question.
Operator: And the next question is coming from the line of Analyst of Barclays. Please go ahead.
Analyst: Hi. This is Jordan Becker on for Etzer Darot. Thanks for taking my question and congrats on the impressive quarter. Maybe just one, if we could expand on any second-half dynamics for oxybates now with a full quarter in the rearview. Maybe if you could provide some more color on any potential competitive pressure from Lumryz specifically. And then on that, maybe any perceived pressure to IH growth down the line if Lumryz is approved in IH?
Samantha Pearce: Yes, I am happy to take that question on Xywav. We are very pleased with the continued momentum for Xywav. $408 million this quarter, 18% revenue growth and a really healthy 12% volume growth. We continue to see really good patient adds—425 net patient adds in the quarter, most of them continuing to come from 300 net patient adds for IH, which is consistent with what we have seen in prior quarters. So we finished the quarter with 16,600 active patients. And when we look ahead to the outlook for Xywav for the remainder of the year, obviously, we are very pleased with the momentum that we are taking into the second quarter.
We still have continued strong payer coverage—more than 90% of commercial lives covered. Nothing has changed around the nature of our Xywav business in the first quarter of this year. And our 2026 full-year guidance does include assumptions that generics will build volumes in the second half of the year, as well as the potential for the entry of new wake-promoting agents entering the market in the second half of the year in the NT1 narcolepsy segment. But we believe Xywav will continue to have a really important place in therapy.
We have invested in some really meaningful evidence generation, XYLO and the DUET studies, which show the importance of having a low-sodium option, and the DUET study, which shows just how effective Xywav is as a nighttime agent. We believe those two benefits will continue to resonate strongly with physicians and patients, of course.
Operator: Thank you. One moment for the next question. Our next question is coming from the line of Analyst of Baird. Please go ahead.
Analyst: This is Charlie on for Brian. I was just wondering if you could give us a sense of the size of the opportunity for Epidiolex in the adult and long-term care setting. And maybe some more color on the initiatives you are taking there with the new formulation as well as would be curious to hear—will you be sharing any data from the Phase 1b in focal when you get that, and do you have any idea in terms of timing there as well as what your expectations are for the setting for Epidiolex? Thanks.
Samantha Pearce: I am happy to take the first part of your question in relation to the adult segment, and then I will hand over to Rob to talk about the study. We are very happy with the performance of Epidiolex in the first quarter of this year, $250 million, 15% revenue growth, and 16% volume growth. As you probably recall, Epidiolex was launched initially very much as a pediatric drug, and we have seen really good penetration in that segment, a leading agent, obviously, for pediatric patients. One area that we do continue to see opportunities in is in that adult segment, particularly in long-term care facilities.
So we have made some specific investments there with a dedicated team focusing on those facilities. And we have also invested in a diagnostic tool, REST-LGS tool, because we know that adult patients with LGS often go undiagnosed. So we have supported physicians to help ensure that those patients can get a definitive diagnosis and benefit from Epidiolex. In addition to that, one of the hallmarks of Epidiolex is the very long persistency that we see. But we do see an opportunity to drive that even further.
We know that patients that are enrolled onto our JazzCares program, which also gets the support of a nurse navigator, stay on treatment longer, so we have a particularly focused effort now on ensuring that as many patients as possible can benefit from our JazzCares suite of services, and we believe that will drive even longer durations of treatment for Epidiolex. In addition to that, we are making quite significant investments in evidence generation.
We have the EPICOM study in TSC and the BECOME survey, which has been focused on adults, which really just underlines the benefit that Epidiolex has not just for the control of seizures, but also for controlling some of the non-seizure symptoms that these patients experience as well. That is one of the very significant differentiating benefits of Epidiolex. So overall, we are very encouraged by the momentum that we have with Epidiolex but also really see a lot of long-term potential to continue to grow Epidiolex into the future, particularly in that adult segment.
Robert Iannone: Thanks for the question on the focal seizure study. We are super excited about it. There is a lot of interest from epileptologists to more formally evaluate Epidiolex in this setting. As you know, doctors and treaters think about epilepsy in terms of types of seizures, and we have lots of data showing activity of Epidiolex across really every type of seizure with some preliminary evidence in focal onset seizures as well. This is an evidence generation study to go deeper into this particular population, and we would intend to publish this as soon as we have data available to do so. We have not given any specifics on that yet.
After a little more time elapses and we get a good sense of the enrollment rate, we may be able to update further.
Operator: Thank you. One moment for the next question. Our next question is coming from the line of David A. Amsellem of Piper Sandler. Your line is open.
David A. Amsellem: Hey. Thanks. So I have a long-term competitive landscape question on your business. So your competitor has valroxabate, the sodium once-nightly, or potential no-sodium once-nightly product that is in development. To the extent that reaches the market, can you talk about how that could impact your Xywav business, both in terms of narcolepsy and the IH setting? And just in general, how are you planning to respond competitively to overall a more crowded landscape? The obvious is, of course, with the orexins, but also next-generation oxybate products as well. Thanks.
Renée Galá: Maybe I can step in on that, and then I will ask Rob to comment on how we are viewing orexins. I would first point to the fact that Xywav has been competing for the last two years with a number of high-sodium options on the market. Over that time, we have not only built a strong group of patients that are relatively persistent in terms of their use of oxybate, but also the specific relief and flexibility that they receive from Xywav, and it is the only product available for IH. We have done a lot of work in the market in terms of disease awareness.
One of the areas that we have invested quite a lot in that Sam has spoken to earlier is the patient support services. I think that is highly differentiating for Jazz Pharmaceuticals plc in terms of the extent of our services and the way that we have deployed those. We will continue to ensure that the unique differentiating benefits of Xywav as well as various support services are well understood in the market. I would also note that we do, from a patent perspective, have a lot of confidence in our overall patent estate.
So when you are thinking about the various programs that are out there that may be for a 505(b)(2) sort of path, from that perspective, we do have robust patents that include many Orange Book–listed patents out to 2033 and 2037, and then an Orange Book–listed IH patent out to 2041. But maybe I will also invite Rob to comment with respect to orexins coming into the market and our view there.
Robert Iannone: Yes, we have been following orexins carefully, and our conclusion is that it is likely to be complementary to Xywav. As Sam mentioned, alluding to the DUET study, we have significant data showing that the root cause in hypersomnia, such as narcolepsy type 1 and 2, as well as IH, has really disrupted nighttime sleep, and oxybates are the only therapy that can address the disrupted nighttime sleep directly. And Xywav, of course, is the only low-sodium formulation that we believe is safest for patients who are at a high risk for cardiovascular outcomes. Certainly, the orexins are showing to be potent daytime alerting agents.
Some preliminary data are showing, though, that you can have insomnia, especially with the longer half-life formulations. The limited PSG data that are out there suggest that they certainly are not improving disrupted nighttime sleep and may actually, in the first half of the night, be impacting it negatively with the reports of insomnia. So we continue to think that this is an important space to follow. We have an orexin in development still, but we think, ultimately, this is going to be complementary to Xywav.
Operator: Thank you. One moment for the next question. Our next question is coming from the line of Mohit Bansal of Wells Fargo. Please go ahead.
Mohit Bansal: Great. Thank you very much for taking my question, and congrats on all the progress. Just want to ask about the Zepzelca IP here. I see a few new Orange Book–listed patents here since 2025, so they go all the way to 2040. So how should we think about the life of Zepzelca beyond 2029 at the compound-of-matter patent at this point? Thank you.
Renée Galá: Thanks, Mohit. This is Renée. We do have a strong patent estate for Zepzelca, and as you noted, we have multiple patents that extend out to 2040. We are also pursuing multiple new patents with the Patent Office that would also extend out to that timeframe, with additional applications, whether that be combo therapies, formulations, or methods of treatment. Stepping back and speaking to the ANDA filers that we have disclosed, we have filed suit against all five ANDA filers, and as the result of filing that suit, a stay of approval is in effect for up to 30 months as imposed by the FDA.
While we are not going to speak broadly to active litigation, we do feel that we have a strong patent estate, and as we have more clarity and information on that, we will be certain to share that.
Operator: Thank you. One moment for the next question. Our next question is coming from the line of Jason Matthew Gerberry of Bank of America Securities. Please go ahead.
Jason Matthew Gerberry: Hey, guys. Thanks for taking my questions. Just one for Phil on Xywav. I apologize if I missed this, but you, at the beginning of the year, guided to flat to mid-single-digit growth for Xywav. Given growth of nearly 20% in 1Q, just wondering if we should be assuming that we are coming in towards closer to the high end of that number? Or were there some one-time dynamics in the 1Q number to call out? And how should we think about zanidatumab pricing OUS and any MFN-related considerations?
Philip L. Johnson: Thanks for the question, Jason. On Xywav in the U.S., really pleased, as Sam mentioned, with the great execution of our field-based team. In terms of underlying growth, we had volume growth of about 12% here in the first quarter. There was a bit of additional pickup coming from net price, primarily gross-to-net favorability with both mix of business and then patients successfully transitioning more quickly than in the past back onto their insurance in that first quarter reauthorization period. That is something that is more of a first-quarter phenomenon.
We would not expect to see that kind of net price pickup quarter on quarter as we get into Q2 through Q4, but definitely pleased with Xywav performance in the first quarter—it sets us up nicely for achieving the full-year guidance. I think that also applies to the total revenue guidance as well, not just Xywav. And then for the MFN, zanidatumab—right now, the MFN considerations, as you know, are a bit uncertain. We have got some sort of conflicting input out there; certainly GLP and GARD are proposed to use a basket of ex-U.S. countries to provide reference pricing for the U.S.
We will certainly be taking that into account as we look at the strategy for getting ZYHERA to patients outside of the U.S., which is certainly a priority of ours and one that we will need to take account of the current situation here in the U.S. as we move forward. Not sure, Sam, if you would like to add any of your thoughts from a commercial perspective, or Renée more from a corporate strategic perspective.
Renée Galá: I think you covered it nicely, Phil.
Jason Matthew Gerberry: Great.
Operator: Next caller, please.
Operator: Thank you. And our next question will come from the line of Ami Fadia of Needham & Company. Please go ahead.
Ami Fadia: Hi. Good afternoon. Thanks for taking my question. I had a follow-up on the comments related to the oxybate franchise, particularly Xywav. I think at the beginning of the year, you talked about anticipating the potential for some additional headwinds either on the pricing side or just in terms of access with the entry of generics. Maybe if you could talk about some of the dynamics around whether you see any pushback on the use of Xywav, particularly in narcolepsy, and how you see the utilization in narcolepsy evolve with more generics on the market?
And then just on the Midevo ACTION trial, can you talk about which interim OS analysis will be done by the time you have the data readout in late 2026, early 2027, and your confidence around the timeline of that readout? Thank you.
Samantha Pearce: I am happy to take the question relating to Xywav. Yes, of course, we have seen two multisource generics enter the market in Q1. As yet, we have not seen any impact on Xywav's business. As I mentioned previously, we continue to have strong payer coverage supporting the use of Xywav, so nothing really has changed in the nature of our business for Xywav. But, of course, it is still early days for the generics in the market. We do anticipate that as their volume grows through the course of the year, then we may start to see some actions taken by payers that may include utilization management. We do not know yet.
But we are very confident that Xywav offers a really important and differentiating option for patients—being the only low-sodium option, the only product approved for IH. And, of course, it has already demonstrated how effective it is as a nighttime agent and the impact that has on daytime symptoms. We have carried strong momentum throughout the last twelve months and into this year, and we are in a strong position as we go into Q2.
Philip L. Johnson: Sam, just to add one thing real quickly as we think about what we are seeing with Xywav before we go on to Rob for the data. Certainly the dynamics are a bit unusual in the first quarter given reauthorization, but I do think we are seeing continued support by patients and physicians of the unique benefit that Xywav offers. Think about looking at the net patient adds. Lumryz net patient adds were announced as roughly 100 adds this quarter, like the 100 last quarter.
Our numbers just in narcolepsy have been larger than that in each of those two quarters—again underscoring this unique benefit that only Xywav can offer and the safety advantage it confers being valued by patients as well as physicians. So we are in a great position from that perspective as well as we think about the back part of the year and how things could play out.
Robert Iannone: Yes. So, Ami, the ACTION trial is an OS-based endpoint and there is one interim analysis and then a final analysis. The projections we gave are based on our current understanding of the events because it is an event-driven trial. Certainly, if the events slow over time, that could change. But we will update as appropriate as time goes on.
Operator: Thank you. One moment for the next question. And our next question is coming from the line of Analyst of Deutsche Bank. Please go ahead.
Analyst: Hey there. Thanks for taking my questions. I first wanted to ask on the timing of a potential NCCN guideline incorporation for zanidatumab in GEA. Do you have any sense of, relatively, when that might occur versus the PDUFA date, and how important is a category 1 recommendation to drive uptake? And then in breast cancer for zanidatumab, I wanted to get a sense of how you are thinking about the opportunity size in the different settings. Obviously, you are looking at post-ENHERTU, but I think you are also looking at neoadjuvant/adjuvant. I was just curious as to your thoughts on the size of the opportunity in those various settings.
Robert Iannone: Great. On the NCCN guidelines, we proactively submitted the abstract data because it was available. We will certainly update NCCN with the full manuscript as soon as that is available, and we hope that gives them everything they need to make a prompt decision on that and adoption, which we expect. Certainly, we think the data speak for themselves. Head to head against Herceptin, zanidatumab definitively wins. It is clear that tislelizumab is adding and likely to be synergistic with zanidatumab, as demonstrated by the activity in the PD-L1 negative subset, supporting its use upfront with tislelizumab. We think those data speak for themselves, and that should be reflected in NCCN.
Samantha Pearce: Sorry, just to finish off the remainder of that question there. NCCN guidelines inclusion is obviously important. We think that the data support a category 1 inclusion. If it comes before the launch, then that will open up access ahead of regulatory approval. Of course, we do not promote ahead of regulatory approval, but certainly that will make it easier for physicians to provide access to their patients. And yes, the breast cancer opportunity is obviously very significant—significantly larger than either the BTC opportunity or the GEA opportunity—with many more patients that can potentially benefit from zanidatumab. So we are excited, obviously, about that for the long-term potential for ZYHERA.
Operator: Thank you. That does conclude today's Q&A session. I would like to turn the call over to Renée Galá, CEO, for closing remarks. Please go ahead.
Renée Galá: Thanks, operator. I would like to close today's call by thanking all our partners and stakeholders for their continued confidence and support. We look forward to sharing further updates on the potential approval and launch of ZYHERA.
