Jazz Pharmaceuticals PLC (JAZZ) Q2 2025 Earnings Call Transcript

Jazz Pharmaceuticals PLC (NASDAQ: JAZZ) Q2 2025 Earnings Call dated Aug. 05, 2025

Corporate Participants:

Jack Spinks — Investor Relations

Bruce Cozadd — Chief Executive Officer

Renee Gala — Chief Operating Officer

Rob Iannone — Chief Medical Officer

Phil Johnson — Chief Financial Officer

Analysts:

Jason Gerberry — Analyst

Jessica Fye — Analyst

David Amsellem — Analyst

Andrea Newkirk — Analyst

Akash Tiwari — Analyst

David Wang — Analyst

Ami Fadia — Analyst

Joseph Thome — Analyst

Joon Lee — Analyst

Ashwani Verma — Analyst

Mike Riad — Analyst

Mohit Bansal — Analyst

Gary Nachman — Analyst

Basma — Analyst

Presentation:

Operator

Good day, and thank you for standing-by. Welcome to Jazz Pharmaceuticals 2025 Second 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. [Operator Instructions] Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your first speaker today, Jack Spinks, Executive Director of Investor Relations.

Jack Spinks — Investor Relations

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2025 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors should also refer to the press release we issued earlier today that is available on our website.

On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renee Gala, President and Chief Operating Officer and recently announced Chief Executive Officer, effective August 11; Rob Iannone, Executive Vice President, Global Head of R&D and Chief Medical Officer; and Phil Johnson, Executive Vice President and Chief Financial Officer.

On slide 2. I’d 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 and goals, which involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in those forward-looking statements. We encourage you to review the statements contained in today’s press release, in our slide deck and the risks and uncertainties described under the caption Risk Factors in our Annual Report on Form 10-K for the fiscal year ended 31st December 2024, and our subsequent filings with the SEC, including our quarterly report on Form 10-Q for the fiscal quarter ended June 30th, 2025, which identifies certain factors that may cause the company’s actual events, performance and results to differ materially from those contained in the forward-looking statements made on today’s webcast. We undertake no duty or obligation to update our forward-looking statements.

As noted on slide 3, 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’ll now turn the call over to Bruce.

Bruce Cozadd — Chief Executive Officer

Thanks, Jack. Good afternoon, everyone. Thank you for joining us today to discuss Jazz’s second quarter 2025 results. Starting on slide 5, I’d like to congratulate Renee on her unanimous selection by the Jazz Board of Directors as President and CEO. I’m confident Renee is the right leader to build on Jazz’s momentum and serve as a catalyst in driving long-term growth. After working with Renee closely for more than five years, I’ve seen firsthand that she has the right skill-set and experience to further drive innovation, while nurturing the culture of purpose and patient impact that is at the center of everything we do at Jazz.

Since co-founding Jazz in 2003, I’ve had the extraordinary privilege of leading the company through its growth and significant diversification that has transformed the business into the fully integrated biopharma company it is today. I’ll continue serving as Chairman of the Board of Directors, providing strategic guidance and look forward to seeing Jazz continue delivering for patients, employees and shareholders.

Now turning to slide 6, Jazz continues to demonstrate considerable progress across commercial, R&D and corporate development. We remain confident in the strength of our diversified portfolio and excited about the potential for future growth as we prepare for the anticipated approval of Dordaviprone and approval of Zepzelca in an earlier line of treatment.

We’re approaching a significant milestone for Dordaviprone with the upcoming FDA PDUFA target action date of August 18. We added Dordaviprone to our pipeline through the acquisition we closed in April, enhancing our presence in rare oncology. Given its patent protection into 2037 with potential to receive patent term extension and the opportunity for expanded use in the frontline setting, we view Dordaviprone as a meaningful and durable revenue opportunity for Jazz.

In addition, we have the right capabilities in place to deliver a successful commercial launch and are positioned to initiate key activities immediately upon receiving FDA approval. We remain excited about bringing this first-in-class therapy to patients with H3 K27M-mutant diffuse glioma, who currently have very limited treatment options.

Additionally, on the regulatory front, I’m pleased that Ziihera was recently granted conditional marketing authorization by the European Commission for advanced HER2+ Biliary Tract Cancer or BTC, and we look forward to the upcoming October 7th PDUFA target action date for Zepzelca in first line maintenance for extensive stage Small-cell lung cancer.

Turning to our commercial business. In the second quarter of 2025, we generated over $1 billion in total revenue across our portfolio, led by our neuroscience assets. Xywav grew 13% year-over-year with robust net patient adds seen across both Narcolepsy and Idiopathic Hypersomnia

Or IH. Xywav remains the only low sodium oxybate, the number one branded treatment for narcolepsy as measured by revenue and the only FDA approved therapy to treat IH.

Epidiolex continues to have strong underlying demand and we remain confident in its blockbuster potential. While our oncology portfolio is facing near-term headwinds, we remain confident in the outlook for growth, driven by multiple near-term catalysts, including the upcoming dordaviprone PDUFA for the treatment of recurrent H3 K27M-mutant diffuse glioma, Zepzelca’s potential move into first line maintenance in extensive stage small-cell lung cancer and the topline data readout from zanidatamab’s Phase 3 firstline Gastroesophageal Adenocarcinoma or GEA trial expected late in the fourth quarter of 2025.

Turning to our pipeline. At the ASCO Annual Meeting in June, we presented potentially practice changing Phase 3 data for Zepzelca and updated Phase 2 data, including long-term survival for zanidatamab, which demonstrated unprecedented advances in their respective tumor types. Our zanidatamab clinical development program continues to progress well and enroll patients across our numerous ongoing registrational trials. Additionally, we initiated a new Phase 2 trial in neoadjuvant and adjuvant HER2+ breast cancer.

With the first half of the year complete, we’ve revised our financial guidance, including a modest reduction in the midpoint of our revenue guidance, while reductions in SG&A, R&D and effective tax rate guidance support raising the lower end of our A&I and EPS guidance. We generated robust operating cash flow in the first half of the year and remain confident in the overall strength of the business.

In summary, we’re focused on execution and delivering innovative therapies for patients and their families. Our diversified portfolio, robust pipeline and disciplined approach to capital allocation position us well for sustainable long-term growth.

I’ll now turn the call over to Renee to discuss our commercial performance, after which Rob will cover our R&D pipeline. Phil will then provide a financial overview and discuss our updated guidance. And after that, we’ll open the call to Q&A. Renee?

Renee Gala — Chief Operating Officer

Thanks, Bruce. I’m thrilled to be stepping into the CEO role to build upon Jazz’s incredible success and transformation over the last several years. I’d like to thank the board for their trust and confidence in me and Bruce for his dedicated leadership of Jazz over the past two decades. I believe this company has immense potential and I look forward to continuing the important efforts underway and working with our team to drive greater value for our patients and shareholders. I know there may be questions about potential changes to Jazz’s future direction. Right now, my focus is on ensuring a smooth transition into the CEO role. As we shape our next phase of growth, I plan to listen and gather insights from a broad range of internal and external voices. And as decisions are made, they will be shared broadly. In the meantime, I appreciate your patience and support and I look forward to engaging on this topic in the future.

Now, I’ll begin on slide 8 to discuss the progress of our commercial portfolio. Starting with our sleep therapeutic area, total sleep revenue, which includes Xywav and Xyrem net product sales plus royalties from high-sodium oxybate authorized generics or AGs was $505 million in the second quarter of 2025. Xywav delivered another strong quarter with net product sales increasing 13% year-over-year to approximately $415 million. As the only low-sodium oxybate therapy, the benefits of Xywav in reducing sodium intake and individualized dosing continue to resonate with patients in HCPs. This is reflected by the approximately 625 net patient adds across both narcolepsy and IH exiting the second quarter.

We continue to focus on strong execution and enabling as many patients as possible to benefit from low-sodium Xywav. Our field teams are generating strong demand with medical science liaisons and a suite of patient services like field nurse educators, working in an integrated fashion to educate HCPs and help patients from their initial diagnosis through titration of Xywav.

We’ve been particularly pleased with the continued momentum in IH, where we had approximately 400 net patient adds this quarter. Our consumer targeted digital and media campaigns are performing well and building disease awareness and patient education. These initiatives, coupled with our ongoing HCP education around proper diagnosis and identifying appropriate patients who can benefit from Xywav, are contributing meaningfully to growth in IH, where Xywav is the only FDA approved therapy.

We were pleased with our robust medical presence at the APSS Annual Meeting in June with 24 total presentations, including 19 posters and five oral presentations. These included results from the Phase 4 open-label XYLO trial showing that a switch from high-sodium oxybate to the same dose of low-sodium oxybate was associated with clinically meaningful reductions in blood pressure. Additionally, two presentations from the DUET trial evaluating sleep architecture demonstrated the effectiveness of Xywav on improvements in sleep quality among patients with IH or narcolepsy. These data presentations continue to strengthen the clinical evidence supporting Xywav’s differentiated therapeutic value.

Moving to slide 9, underlying demand for Epidiolex remained strong with second quarter net product sales of approximately $252 million, representing a 2% increase compared to the same quarter in 2024. Year-over-year revenue growth was impacted by a number of factors, including US inventory dynamics. As noted on a prior call, we experienced an earlier than expected build of inventory in the second quarter of 2024, which negatively impacts our current year-over-year growth rate. Based on typical seasonality, we anticipate a gradual build in inventory throughout the second half of this year.

Our Epidiolex field teams in the US and Europe are executing well, focusing on the product’s unique differentiation, including the robust body of evidence supporting both seizure and non-seizure benefits. The adult segment and long-term care facilities continue to be a focus of growth for Epidiolex.

LGS has historically been underdiagnosed in adult patients due to the evolution of symptoms over time. However, the refractory epilepsy screening tool for LGS is helping some providers to more readily identify adult patients living with LGS. With our ongoing momentum, we continue to expect Epidiolex to reach blockbuster status this year.

Moving to oncology on slide 10. Rylaze net product sales were approximately $101 million in the second quarter of 2025, a decrease of 7% year-over-year. Updates to Children’s Oncology Group pediatric ALL treatment protocol that impacted the timing of asparaginase administration, which were first recommended a year-ago have been broadly adopted. Although claims data indicate that pediatric asparaginase use as a class remains below pre-protocol implementation levels.

Rylaze use in pediatric ALL patients relative to the asparaginase class as a whole has remained broadly stable. We are focused on continuing efforts to ensure switching to Rylaze at the first sign of hypersensitivity reaction and expanding our presence in the adolescent and young adult market, we view these as the greatest opportunities for Rylaze growth.

On slide 11, Zepzelca net product sales for the second quarter of 2025 were approximately $75 million, a decrease of 8% year-over-year. While we have seen increased competition in the second-line small-cell lung cancer setting, Zepzelca continues to be a highly prescribed treatment for patients. Of note, the adoption of immunotherapy in first-line limited-stage small-cell lung cancer is improving PFS and delaying the progression of patients into the second-line setting, thereby reducing the number of patients available for second-line treatment.

Importantly, we believe the IMforte data presented at ASCO will set a new treatment standard for extensive-stage small-cell lung cancer patients in the first-line maintenance setting. Our sNDA has been granted priority review with the PDUFA target action date of October 7th, 2025, and we have submitted the data for potential inclusion and NCCN Guidelines, which is generally a path for broader uptake and reimbursement. This potential to move into first-line maintenance therapy represents an important opportunity to enable patients to benefit from Zepzelca earlier in their treatment and represents an opportunity to redefine the treatment paradigm in first-line extensive-stage small-cell lung cancer.

Moving to slide 12 on Ziihera, we recognized approximately $6 million of net product sales in the second quarter of 2025, which given the patient population in BTC is aligned to our expectations at this early-stage of launch. We are receiving feedback from oncologists that continues to confirm the real-world clinical profile at benefit matches what was observed in clinical trials.

We’re pleased with this positive feedback as HCPs gain experience and confidence with prescribing Ziihera. As we look ahead to GEA, we would anticipate rapid NCCN Guideline inclusion if data are positive and strong clinical adoption following potential regulatory approval. We believe zanidatamab has the potential to be the HER2 targeted agent of choice. Finally, we were pleased the European Commission granted conditional marketing authorization for second-line HER2+ BTC in June, and we are initiating the rolling launch across Europe.

I’ll now turn it over to Rob, for an update on our pipeline and upcoming milestones. Rob?

Rob Iannone — Chief Medical Officer

Thank you, Renee. Starting on slide 14, we have an exciting pipeline and are making substantial progress on key programs with additional milestones expected this year. In oncology, we were pleased the FDA granted priority review of our sNDA for Zepzelca with the PDUFA target action date of October 7 for maintenance therapy in first-line extensive stage small-cell lung cancer for patients who have not progressed during induction chemotherapy. The submission was based on the compelling Phase 3 and IMforte data presented at ASCO. We believe these results are practice changing and we have submitted the data for potential inclusion and NCCM guidelines.

Regarding our Phase 3 first-line Horizon GEA zanidatamab trial. Given that we’re now in early August, we do not expect to announce top-line data in the third quarter. Based on the current event projections, we do continue to expect we will announce top-line data late in the fourth quarter of 2025, consistent with our prior disclosure of the second half of 2025.

We are also excited to highlight the recently initiated Phase 2 trial studying zanidatamab as neoadjuvant and adjuvant therapy in breast cancer. This trial aims to reduce the burden on patients with early breast cancer, increase pathologic complete response rates, improve long-term outcomes and reduce overall toxicity. The randomized open-label trial will assess the past CR rate of neoadjuvant to zanidatamab and taxane with or without carboplatin versus a regimen containing a taxane, carboplatin and trastuzumab and pertuzumab. Following surgery, patients with past CR will continue on zanidatamab and those without CR will receive TDM-1 as adjuvant therapy and will be followed for event free survival.

Turning to our zanidatamab development program on slide 15, the ongoing clinical trials continue to progress and we’re expanding the program with the new trial immunoadjuvant and adjuvant breast cancer. The EmpowHER-BC-303 trial evaluating zanidatamab plus physician’s choice of chemotherapy versus trastuzumab plus physician’s choice of chemotherapy and metastatic breast cancer patients who are intolerant to or have progressed on TDXD treatment continues to progress well with enrollment and strong interest from sites. Our first-line confirmatory BTC trial also continues to advance as thus the Phase 2 brain tumor trial.

Moving to slide 16, we were pleased to close the Chimerix transaction in April and welcome our new colleagues to Jazz. We look forward to the upcoming PDUFA target action date of August 18 for Dordaviprone, a groundbreaking first-in-class small-molecule in development for H3 K27M-mutant diffuse glioma, a rare high-grade brain tumor that most commonly affects children and young adults and the opportunity to bring hope to patients who currently have no approved drug therapies.

The confirmatory action trial in the front-line setting is ongoing and enrollment remains on track. We are continuing to assess timelines for the trial and we’ll provide an update as appropriate. Our current focus is on the NDA for Dordaviprone and potentially bringing this therapy to patients as soon as possible. This represents exactly the kind of transformative innovation we strive to deliver for patients at Jazz. We intend to host an investor webcast to discuss the commercial launch of Dordaviprone following approval.

Now turning to slide 17, I’ll highlight the encouraging data we presented at ASCO this year that support my confidence in our pipeline. In results from the Phase 3 IMforte trial, which have been published in the Lancet, Zepzelca in combination with atezolizumab demonstrated a reduced risk of disease progression or death from the time of randomization by 46% and the risk of death by 27% compared to the atezolizumab alone. In addition, the treatment duration for patients receiving zepzelca plus atezolizumab was twice as long as the atezolizumab [Indecipherable] with a median maintenance treatment duration of 4.2 months versus 2.1 months respectively. The combination was generally well tolerated with no new safety signals identified.

We are also highly encouraged by results from the long-term Phase 2 GEA trial of zanidatamab, which showed a remarkable 36.5 month median overall survival after four years of follow-up in centrally confirmed HER2+ first-line patients with GEA. These promising results provide additional confidence as we await the Phase 3 Horizon GEA readout anticipated late in the fourth quarter of this year.

An oral presentation of the safety and efficacy of dordaviprone from an integrated analysis showed promise in shrinking tumors in both adults and pediatric patients with an encouraging disease control rate. The results were in line with earlier studies and side effects for generally mild.

Now I will turn the call over to Phil for a financial update. Phil?

Phil Johnson — Chief Financial Officer

Thanks, Rob. I’ll start on slide 19 with our top-line results. As a reminder, our full financial results are available in our press release, which is available today and in our 10-Q, which will be filed tomorrow morning. In the second quarter of 2025, we generated $1.05 billion in total revenues. This represents an increase of 2% over last year’s quarter and was driven by robust Xywav growth of 13%. As Renee mentioned, net patient adds were particularly strong, providing great momentum as we move into the second half of the year. Epidiolex growth moderated to 2% this quarter, driven by several factors, including year-over-year inventory dynamics in the US as Renee mentioned earlier. Despite inventory dynamics, we continue to be pleased with the demand we’re seeing for Epidiolex.

In total, our oncology products decreased 1% compared to the second quarter of 2024 as lower sales of Rylaze and Zepzelca were largely offset by higher sales of Ziihera, Defitelio and Vyxeos. Looking forward, we remain optimistic and confident in the future of our oncology franchise and are ready to successfully execute on the rolling launch of Ziihera for BTC in Europe and the potential near-term launches of Dordaviprone in our current H3 K27M-mutant fuse glioma and of Zepzelca in the first-line maintenance setting for small-cell lung cancer. In addition, we look forward to the upcoming Phase 3 first-line GEA readout for zenidatamab.

Adjusted net loss for the second quarter of this year was $505 million. This loss was entirely driven by the $905 million non-tax deductible acquired IPR&D charge from the Chimerix acquisition. We continue to generate significant cash, recording $519 million of operating cash flow in the first-half of the year. And even after the acquisition of Chimerix and payments to settle certain of the Zyremana Trust claims we announced last quarter, our balance sheet is strong with $1.7 billion in cash and investments at quarter end.

With that context, let’s move to our revised 2025 financial guidance. You’ll see on slide 20 that we’ve narrowed our 2025 revenue guidance by lowering the top end of the range, resulting in 4% growth at the midpoint. This change reflects our assessment halfway through the year that revenue is largely tracking to our expectations with some potential upsides being less likely.

Turning to slide 21, we’ve reduced both SG&A and R&D guidance ranges, primarily because of our efforts to prioritize spend for our highest impact initiatives and to enhance operational efficiency. In addition, we’ve incorporated refined estimates of ongoing Chimerix costs. You’ll note that our revised SG&A and R&D guidance ranges do contemplate higher spending in the second half of the year than in the first half of the year. This uplift is primarily driven by the inclusion of Chimerix expenses for the full period, including the ramp of launch activities for Dordaviprone. We’re also increasing support for Ziihera and Zepzelca, making targeted investments behind Xywav and Epidiolex and our accelerated activity across several zenidatamab clinical trials.

Looking at the second half of the year, I’d like to make a detailed comment that may help with your modeling as well as a higher level comment on how we’re positioned. As you develop your expectations for sales of our US oncology products, please note that we’ll have 14 shipping weeks in the third quarter and 13 shipping weeks in the fourth quarter. Year-on-year growth rates will be affected by the fact that we had the opposite pattern last year with 13 shipping weeks in the third quarter and 14 shipping weeks in the fourth quarter. Hopefully, this information will minimize any surprises based on the calendar.

Stepping up to a higher level, in the back half of the year, we have several commercial catalysts that position us for growth. Our disciplined approach to capital allocation ensures we’re investing strategically in our high priority R&D programs and our lead commercial products. Our strong balance sheet and cash flow enables us to engage in value creating corporate development as we did with Chimerix. We’re confident this focused execution of our strategy can drive long-term growth and we look forward to realizing the significant opportunities ahead.

I’ll now turn the call back to Bruce for closing remarks.

Bruce Cozadd — Chief Executive Officer

I’ll conclude our prepared remarks on slide 23. We remain well positioned to deliver shareholder value as we head into the second half of 2025. We continue to focus on optimizing our commercial execution, advancing key development programs and maintaining our commitment to patients who depend on our medicines. I’m pleased with the robust net patient adds exiting the quarter for Xywav, the only low-sodium oxybate and continue to anticipate Epidiolex will reach blockbuster status this year. As our oncology portfolio overcomes near-term headwinds, we expect to return to growth driven by new opportunities, we look forward to our two upcoming PDUFAs, one for Dordaviprone this month and one for Zepzelca in October, as well as the topline readout of the Phase 3 Horizon GEA clinical trial expected late in the fourth quarter of 2025. Again, I’d like to congratulate Renee and thank our talented employees for their dedication and commitment to innovating to transform the lives of patients and their families. That concludes our prepared remarks.

I’d now like to turn the call over to the operator to open the line for Q&A.

Questions and Answers:

Operator

Thank you. At this time, we will conduct a question-and-answer session. [Operator Instructions] Our first question comes from Marc Goodman at Leerink. Mark, your line is open.

Our next question comes from Jason Gerberry at Bank of America. Your line is open.

Jason Gerberry

Hey, guys. Thanks for taking my questions and congrats, Renee and Bruce, it’s been awesome working with you. kind[phonetic] of miss you? So my question is, you know, what’s driving the strength of Xywav and IH, specifically, the patient adds look like they’re sustainable and going up. And just kind of curious, if I can get your perspective on the sustainability of that rate of patient adds into next year? thanks.

Bruce Cozadd

Renee you want to jump-in on that? Renee looks like you’re still on mute. While we’re waiting for Renee to figure out how to get off mute unless somebody else can hear, I’ll just say Jason, it’s been a pleasure working with everyone over the past many years that Jazz has been a public company since — excuse me, 2007. And for a couple of you out there on the buy-side and the sell-side, I’d probably go back 30 years. So it’s been a real pleasure getting to know you all, and I will be watching Jazz as forward progress as all of you will under Renee’s leadership.

With that, Renee, over to you.

Renee Gala

Yeah. Can you hear me now?

Bruce Cozadd

Yes, we can.

Renee Gala

Okay, great. Sorry, I’m not sure what happened there. So thanks, Jason. We were really pleased with the growth that we saw in the quarter with Xywav both in narcolepsy and in idiopathic hypersomnia. In terms of IH, we do see that as being an area where we — we see the most opportunity for growth as Xywav is the only FDA approved therapy.

So in terms of what’s driving the growth. We have seen some really strong execution across our field teams and our investments. Our consumer targeted digital and media campaigns are performing really well. We have invested quite a bit in building disease awareness and patient education because this of course is an area where in the past, if you haven’t had an approved therapy, there’s not necessarily a large incentive to go through the process of getting diagnosed.

And then I would say also our field nurse educator program is particularly helpful with IH patients. When you think about starting oxybate therapy, there is greater persistence once you have titrated up to an efficacious dose, the field nurse educators assist with this. And in particular, with this community of IH being less familiar with oxybate therapy as compared to narcolepsy, that’s been another really helpful service that we’ve been providing to patients and is helping our persistence and overall growth.

Jason Gerberry

Thank you.

Operator

Our next question comes from Jess Fye at JP Morgan.

Jessica Fye

Hey guys, good afternoon and thanks for taking my question and congrats to Renee on the new role into Bruce on retirement. I wanted to ask about Zani for the Phase 3 trial coming up. If I recall, Jazz’s topline updates have historically been more qualitative in nature with numbers to follow later. Is that how we should think about the Zani top-line or could there be potential for any numbers this time around? And if the update is more qualitative, can we expect to hear comments on both zani arms?

Bruce Cozadd

So Jess, I’ll jump-in first and then see, if Rob wants to add anything. Typically, we’ve tried to give important top-line results in terms of have we hit or not a primary endpoint or you know certain pre-specified secondary endpoints if we think they’re germane and important while preserving our ability to publish and present at major conferences by not sharing all the information.

We often try to give qualitative commentary that helps people understand the clinical meaningfulness of results in other ways, so we’re not trying to leave people completely in the dark, but it’s rare that we go all the way to full statistics. We’re also, of course, often unblinding results and sharing them fairly quickly at the top-line, while continued analysis goes on at a very detailed level as we prepare for regulatory filings and otherwise.

Rob, anything you want to add?

Rob Iannone

I think that was great, Bruce. And I would just say our recent experience with IMforte is probably a good example where we not only set stat sig, but we commented on both endpoints PFS and LS and gave some color around it being clinically meaningful and practice changing.

Jessica Fye

Thank you.

Operator

Our next question comes from David Amsellem at Piper Sandler.

David Amsellem

Thanks. So I had a question on Zepzelca. I know you’ve talked about the competitive headwinds here. Your competitor on its call did cite a growing traction of Tarlatamab in the community setting. And so I’m just wondering out loud, with that in mind, do you see continued headwinds for Zepzelca in second-line? And at what point do you start to see perhaps stabilization with the label expansion? And when do you think we’ll have better visibility into a return to growth for Zepzelca? Thank you.

Bruce Cozadd

Yeah. Renee, you want to take that?

Renee Gala

Sure. I’m happy to jump-in. Can you hear me?

Bruce Cozadd

Yeah. Okay, perfect. So thanks for the question, David. And certainly, we have commented on a couple of different dynamics impacting our sales of Zepzelca. One being the increased competition in the second-line tarlatamab. Now these impacts were in line with our expectations. However, it is having an impact on our overall positioning in the second-line. And then, of course, we’ve also said that we’ve seen increased adoption of IO in the treatment of first-line limited stage small-cell lung cancer. This is the impact of the adriatic regimen and that’s delaying progression of some of those first-line limited-stage patients from the first-line into the second-line. And we can see this trend in claims data. Importantly, we’re really looking forward to the potential approval in first-line maintenance for extensive stage based on the IMforte study data that Rob was just mentioning. So we have our PDUFA date on October 7th. We have already submitted for potential inclusion in the NCCN treatment guidelines. We do expect this data to be practice changing and we do expect as we look at that first-line population to have a larger group of patients and we have talked about the duration of therapy also being longer there. So that’s really what we’re focused on.

David Amsellem

Thank you.

Operator

Our next question comes from Andrea Newkirk at Goldman Sachs.

Andrea Newkirk

Good afternoon. Thanks for taking the question. Maybe as a follow up to a prior one, for Rob, when you think about the sustainability of Xywav’s growth profile in the forward. Is there anything you’re looking to understand from the upcoming orexin data presentations at World Sleep to better inform how you think orexin agonist and oxybates will coexist in the rare hypersomnia space?

Bruce Cozadd

Thanks for the question. I mean, certainly, we’ve only seen limited data. And so I am eager to see as much data as possible, not only in terms of daytime efficacy measurements, but the overall safety and tolerability profile and very, very interested in understanding impact on night-time sleep. As we know learning agents often can disrupt night-time sleep, which is really the root cause of narcolepsy. Narcolepsy patients have substantially disrupted night-time sleep.

For example, on average about 80 awakenings a night with not as much deep sleep, not as much deep sleep or total sleep time. So the impact on night-time sleep where Xywav has its main impact and results and benefits during the day is going to be important. So we continue to think about these two mechanisms as potentially being complementary.

Operator

Our next question comes from Akash Tiwari at Jefferies.

Akash Tiwari

Hey, thanks so much. Rob, you mentioned that for the topline press release for HERIZON-GEA, you could give commentary on whether the PFS would be clinically meaningful and practice changing. Can you kind of prospectively identify what that would look like for Zani in that indication?

And then maybe, Renee, I had asked Bruce, this maybe a year-ago, when you think about core and non-core parts of Jazz and I think Bruce has alluded, there could be parts of jazz that are non-core to the business going forward. You guys have such an esoteric mix of products. How would you define what is core and non-core within the Jazz portfolio? Thank you.

Rob Iannone

Yeah. Thanks for the question. I would say it’s always hard to give a specific number to say. If we observe this, we think it will be practice changing. But this field certainly has evolved over the last 10 to 20 years and you can look at examples of how clinical trials have resulted in change in practice, whether that be from the ToGA trial to establish receptin through the JACOB trial and then more recently KEYNOTE-811 where KEYNOTE-811 had about a two-month median PFS difference and about a four-month overall survival difference.

So I think the benchmarks are out there. We’re very encouraged by the two front-line Phase 2 trials that have been conducted, one recently published at ASCO Society plus chemo with a median overall — survival of 36.5 months, very encouraging, but strong, strong response rate duration of response in PFS as well. And those data were very comparable to the other trial where tislelizumab was added and you saw in some respects incrementally better results as well.

Renee Gala

Yeah, and I’m happy to jump-in on the second question, Akash. So yeah, I appreciate that you are thinking about core and non-core parts of Jazz. And I do think at times, what people miss is at the core of our business, the vast majority of our products are essentially rare disease or orphan disease products. And so while on the surface, they may not always look like they sit together, but the underlying capabilities that are required to identify patients to be able to partner with, interact with patient advocacy groups to understand patient needs to be able to target and engage with physicians in some of the field execution capabilities, those are actually quite similar across a number of our products.

Now I would also say when you look at Jazz over time, there have been a number of businesses, products that we have decided to divest because they did not necessarily fit into the core business that we were looking to drive growth and where we felt we could invest to continue to bring forward. I would say Sunosi is a good example of that. Even though it was a product within sleep, it no longer fit the type of business model that we were focusing on going forward.

So as I’m stepping into the new role, I will be looking at where-is the best place for us to be investing. As I mentioned, I do intend to spend time listening, talking to both internal and external parties to better inform the direction that we go forward. But we are in an excellent position today with roughly $4 billion of top-line revenue, healthy cash flows and multiple products to be able to invest in both on the commercial and pipeline front as well as continued appetite for corporate and business development.

Operator

Our next question comes from David Wang at Deutsche Bank.

David Wang

Hi, there. Congrats on the quarter end. Thank you for taking my question. So maybe one on Epidiolex. I want to ask about what underlies the confidence there that product will reach blockbuster status this year? Are there any potential headwinds that may be related to seasonality that could impede those growth expectations?

And then on the oxybate franchise, could you just refresh us about potential entry of multi-source oxybate generics near-term and how that might impact the business? Thank you.

Renee Gala

Sure. I’m happy to jump-in on both of those. So with respect to Epidiolex, this is a product that we do remain confident in terms of reaching blockbuster status this year and ongoing growth. It’s also a product that does tend to see seasonality that impacts inventory and as a result can impact our growth when you’re comparing quarter-over-quarter.

And the second quarter is an excellent example of that. We saw strong underlying demand growth, but we also saw atypical inventory build last year. Typically, we see inventory build in the second half. It burns off in the first quarter, sometimes into the second-quarter. But last year, we saw that inventory build start in the second quarter, which therefore, as a result, not seeing that same dynamic in the second quarter of this year means it negatively impacted our growth rate.

We do expect to see a gradual build of inventory in the second half of this year. And the overall growth when you look between 2024 and 2025, it doesn’t actually need to be very high in order to reach blockbuster status. But given the strong underlying demand that we see, we feel highly confident that we’ll achieve that at a minimum.

With respect to your second question.

David Wang

Yeah. Timing of multi-source generics.

Renee Gala

Yes. Sorry, thank you. With respect to the timing of multi-source generics, they have the ability to enter on December 31st of this year. Of course, Hikma has the ability with notification to us to enter at any time. They have had that ability over the last roughly year and a half as well as the ability to extend the A and continue in the AG agreement through the end of 2027.

So if A generic enters on to the market at the end of this year, they will need to have their own REMS to be able to support their product and we continue as a result to really focus on the differentiation of Xywav as the only low-sodium oxybate on the market as the number one treatment within narcolepsy, the number one branded treatment as well as the only product available at approved for IH.

So I think, Phil, you wanted to jump-in and add something as well?

Phil Johnson

Yeah. On Epidiolex real quick, just in terms of the growth that’s required, as Renee mentioned, we finished last year with $972 million in global revenue, effectively need less than 3% growth to get past $1 billion. We did grow 5% in the first half of the year this year. And as you’ll see in the queue, where we have some disclosures on volume growth for certain products, volume growth continued to be robust at 6%. So some of these inventory things will fluctuate from period-to-period. As Renee mentioned, we’re really pleased with the underlying demand that we’re seeing for the product.

Operator

Our next question comes from Ami Fadia at Needham.

Ami Fadia

Good evening. Thanks for taking my question. Congratulations to Renee on in your role and to Bruce and your retirement. I’m sure you’ll be missed. My question is a follow up on the Zani GEA trial. Given that you’ve increased the enrollment of the study somewhere in early 2024, do you think you’ll have data that will be mature enough for you to have a look on OS or would you need to wait for the next look there? And what is the bar for showing a trend towards OS benefit? Is it simply a hazard ratio under one or something more specific?

And then just with regards to the disclosure that we can expect in the fourth quarter, with regards to Arm C, how much of an improvement would you need to see versus Arm A or Arm B to indicate that adding tislelizumab is sort of incremental for PD-L1 patients? Thank you.

Bruce Cozadd

Thanks, Ami, for the questions. So as a reminder, we have three planned overall survival analyses. The first is time for when we do the one and final PFS analysis. And so certainly, it doesn’t have the full maturity that we’ll have even at the second, but certainly the final. However, the additional time, as you pointed out in getting to the PFS endpoint certainly improves the power in OS relative to what we might have had a year ago. So improves our chances, so to speak.

And your next question was how much of a trend is needed on OS? I think it depends ultimately on the totality of the data. We certainly don’t get into that kind of specific discussions with health authorities etc. But depending on the magnitude of effect of PFS, I think it will all be considered together. There’s a fair amount of precedence in this space in terms of approvals. Of course, the ToGA regimen, Herceptin showed an overall survival benefit and KEYTRUDA had an initial approval, accelerated approval on response rate and full approval on PFS before having mature OS data. So I think there is a certain amount of precedent in this space to go by.

And then lastly, you asked the question of what is the incremental benefit that you need to observe in Arm C versus B in order for that to be approvable. And again, I think it’s a totality of the data question. Certainly, it needs to be contributing meaningfully and the overall benefit risk needs to be favorable.

Operator

[Operator Instructions] Our next question comes from Joseph Thome at TD Cowen.

Joseph Thome

Hi, there, Good afternoon and thank you for taking my question and adding congrats to both Renee and Bruce. Maybe when we talk about the front-line GEA data, this has been pushed a little bit and even though it’s in the current guidance, it sounds like it’s going to be later in the fourth quarter. I guess, can you talk a little bit about your confidence that you know the data will come this year?

And also maybe your confidence that the control Arm A is performing similarly to prior studies? And then maybe just a little bit of an attack on what would that subsequent OS analysis would be? Thank you.

Bruce Cozadd

Yeah. So I would just say we remain blinded overall to the data. But as we get further along in the study and more mature, the assessments around when maturity will come have greater precision. So we have greater confidence in our — projections around that and that has led to a refinement there.

Could you clarify again the last part of the question that you asked?

Joseph Thome

Yeah. I guess just the confidence that the control arm is performing is similarly to prior studies? And then you indicated that there’s several OS analyses and the first one comes with the mature PFS. I guess when is the next one after the mature PFS, when would you expect that to be available?

Bruce Cozadd

Sure. So again, this is an area that this is, I would say, a disease setting that’s been very, very well studied. And if you look at ToGA, JACOB and then KEYNOTE-811, the control arm has performed in a fairly narrow band, and I think it’s reasonable to expect in the modern era that the control arm would be similar to the KEYNOTE-811 results. We’re blinded to the data, so we can’t say for sure how the control arm is performing. But I think that Herceptin and chemotherapy has performed pretty consistently across studies. And so that makes it easier for — planning purposes.

We haven’t given details on exactly how much maturity we would have, for example, on the second interim analysis. But what we have said in the past is when we increase the sample size from approximately 700 to approximately 900, it allowed us to sort of roughly maintain what had been the timing form what had been planned for a final OS analysis while adding a later analysis to be the final and to be better powered.

Operator

Our next question comes from Joon Lee at Truist Securities. Please go ahead.

Joon Lee

Hey, thanks for the updates and for taking our questions. You have a very strong momentum in the narcolepsy franchise, but Takeda is planning to submit an NDA for their orexin antagonist for NT1 and Axsome is also planning to submit an NDA for their NT1 narcolepsy drug in 4Q. So how much impact, if any, do you think the Takeda and Axsome drug could have on your current momentum in the narcolepsy franchise given the potential differences in the scheduling and where are you with your agonist 441? Thank you.

Bruce Cozadd

Renee, you want to take the first part on potential impact of product entry and then, Rob, any update on 441?

Renee Gala

All right. Happy to do that. So I would say, I’ll let Rob comment on some of the mechanisms, but we continue to believe in general that oxybate’s will be complementary to orexins. And then when we lay out the differentiation of Xywav with both low-sodium being the only low-sodium oxybate on the market and flexible dosing, we see that HCPs and patients alike continue to choose the low-sodium based on the underlying cardiovascular conditions that often exist and the propensity to develop cardiovascular conditions on high-sodium oxybates.

And I would say also when you think about other mechanisms, be it wake promoting agents or stimulants, we simply have not seen a meaningful impact with any of those launches on our Xywav momentum. So again, we would think of these as being largely complementary. When you think about the studies that we ran for Xywav. We saw a large number of patients coming in on a background of weight promoting agents and still improved meaningfully with Xywav. Rob?

Rob Iannone

Yeah. I mean, I’d love to add that we have very, very extensive and robust data, not only with Xywav, but in the oxybate field in general and many, many years of patient experience showing that when administered at night and of course, it’s washed out by the time patients wake-up in the morning, there’s a very significant and clinically meaningful impact on night-time sleep, improving key parameters like total sleep time, reducing awakenings after sleep onset dramatically improving deep sleep, consolidating REMS sleep. And that improvement in what’s the — essentially the underlying root cause of the daytime symptoms translates then into more wakefulness and less cataplexy during the day.

Certainly, what we’ve seen of orexins is that they are potent daytime alerting agents. What we haven’t seen is orexins improving meaningfully night-time sleep. The little data that are in the literature shows some consolidation of REMS sleep, but really no impact on total sleep or deep sleep. And we haven’t seen a lot of data around that first part of the night where residual exposure to orexins might actually be disrupting sleep. And that’s partly why we think that these mechanisms are likely to be complementary.

I would mention that at APSS, we recently published more PSG data, both in narcolepsy and IH again establishing the value of Xywav for improving night-time sleep. And then with regard to our own program, as we mentioned, we are already dosing in a small cohort of NT1 patients to evaluate whether JZP441 could progress beyond this stage, depending on the therapeutic index that’s observed and we continue to pursue a backup program that’s in the preclinical space.

Operator

Our next question comes from Ash Verma at UBS.

Ashwani Verma

Hi, thanks for taking my question and congrats on your retirement, Bruce. I wanted to ask a more bigger picture question on your journey. So I know you’ve made pretty massive strides in terms of diversifying the business. But in terms of the stock, there was a pretty significant outperformance from inception, but it’s been range bound for the last, let’s say 10 plus years. So from your perspective, what do you think drove that disconnect?

And then, Renee, any learnings you can take from this experience and how you think you can maximize the shareholder it turn as a CEO?

Bruce Cozadd

Yeah. Ash, thanks for the question. I would say the diversification of our business has been important to have multiple growth drivers, not only the strong continued performance of our sleep business, but the growth in Epidiolex now with its clear long-term runway as well as exciting developments in the oncology portfolio as we’ve continued to add new drugs and expand the opportunity for drugs we do have, with a lot of excitement in particular around zanidatamab.

A place we’ve begun to be more active again is corporate development. We’ve always said that’s part of our strategy. You know, we had a bit of a pause after doing the larger GW transaction as we delevered, but that’s a clear priority for us as you saw with the Chimerix transaction earlier this year, which hopefully leads to near-term launch and a really nice return for us. So we’ve been trying to make that strategic shift over a number of years. It’s been quite dramatic going from 75% of our revenues being dependent on one product, which is now a very, very small percentage of our revenues to having these multiple drivers. So I think we’ve set the company up well as a platform to continue to grow.

And I’ll let Renee talk about where we go from here.

Renee Gala

Yeah. Thanks, Bruce. And I think at this point in time, it might be a bit premature, Ash, to go into a lot of detail. I’m thrilled to be stepping in where the company is today with respect to the strength of the balance sheet, the revenues we’re generating. We have multiple approvals ahead, a very meaningful pipeline readout coming in GEA and a workforce that is highly engaged and passionate about what we do. So I do believe there is really meaningful value to unlock here and I look forward to working with the team to be able to accomplish that. So stay-tuned.

Operator

Our next question comes from Sean Lahman at Morgan Stanley.

Mike Riad

Hey, this is Mike Riad on for Sean. Thank you for taking our questions. I’d also like to extend our congratulations to both Bruce and to Renee. For JZP441, is there a likelihood to get the Phase 1b results this year in NT1 or is that more of a first half ’26 event? Thanks so much.

Bruce Cozadd

We haven’t given specific timing on that. All we’ve said is that it’s a relatively small study. We think in 10 patients or fewer, we can get a read on the therapeutic index and it is an open label trial. So patients are enrolling. And as soon as we have meaningful information, we’ll provide an update.

Operator

Our next question comes from Mohit Bansal at Wells Fargo. Great.

Mohit Bansal

Thank you very much for taking my question. Congrats, Bruce on the retirement and Renee, very well deserved promotion. Looking forward to continue working with you. So my question is regarding Zydus and MSN. And I think last quarter you talked about being important for Zydus. What about other products? Do you see any impact on products like Epidiolex and all as well? And given your portfolio of rare disease drugs, do you think the MFN recent chatter around MFN being impacting the medicaid pricing could have an impact on these drugs as well? Thank you.

Bruce Cozadd

Yeah. Mohit, thanks for the questions. So maybe starting with tariffs. As we had talked on prior call, we do have the opportunity to produce our oxybate products here in the US with a supplier that has more than ample capacity that’s available to us to serve all of our US needs. And we also have a US CMO that does the drug product for Rylaze or for — yes Rylaze as well.

So I would say in terms of the exposure we’ve got to tariffs, similar to we said in the past with steps we’ve taken to mitigate that risk, there really is no exposure to either the existing or some of the ones that are pretended to be coming here in the near future to our 2025 results. And we have a decent amount of coverage for nearly all of our products in terms of US inventory already here locally in the States to cover a decent portion of our 2026 needs as well. Beyond that, we’ll continue to look for ways to go ahead and mitigate that exposure, which could include working with additional third-parties here in the US for other manufacturing. So we’ll continue to keep you updated there.

On MFN, it really is obviously the topic of the last few days here, a lot still is unclear about scope, timeline, operational mechanisms of how the administration may pursue MFN drug pricing, what may happen legally in terms of challenges to proposals that could be coming. So I’d say at this point, it is premature to speculate on what’s going to happen specifically and therefore put some kind of quantification of our exposure. I would say, we do have exposure because we do have US government business and ex-US prices are typically lower than US prices. And some of the products that would have a larger exposure for us based on their proportion of government business would include, for example, Rylaze and Epidiolex. Again, much more to come here, I’m sure in the coming weeks and months and we’ll keep you praised as we have something more specific to you able to say based on concrete proposals.

Mohit Bansal

Helpful thanks.

Operator

Our next question comes from Gary Nachman at Raymond James.

Gary Nachman

Thanks. Bruce, best of luck to you and my congrats as well, Renee. So on Dordaviprone, what’s your confidence level in the accelerated approval at the PDUFA on August 18? Have your conversations been going with FDA, if that’s all been on track? And I know you’ll have a webcast after, but high-level, how are you thinking about that opportunity and how quickly it could ramp-up in that subset of Glioma patients? And can you just roll this into the current oncology sales infrastructure? Thanks.

Bruce Cozadd

Yeah. Maybe in the interest of time since we’re getting short, I’ll just say, Gary, we’ve been in conversations with FDA and we know what the PDUFA target action date is and we hope to have an FDA decision very soon. Renee, maybe I’ll let you comment a little bit on the opportunity. I’ll just say we’re really excited about the opportunity to bring this therapy to patients and think there is a real nice opportunity to make a difference for a lot of patients.

Renee Gala

Yeah. Absolutely. Happy to make a few comments. I mean, first, we are incredibly excited about this potential approval and making this medicine available. This has been a, I would say, true labor of love for our colleagues at Chimerix and we look forward to bringing it to market. We do believe the product will be predominantly administrated in administered in academic settings of excellence.

So we do think — largely a more concentrated call point. And as a result, we are looking at a relatively small but dedicated group to be able to augment our internal footprint, ensure we have sufficient focus on the launch, but also do so in a highly concentrated way. And I would say we’re also excited about this patent portfolio that goes out well into the late 2030s, 2037 with the potential to receive patent term extension. So we also believe this is a durable long lived product. More to come though with respect to our launch meeting.

Operator

Our next question comes from Marc Goodman at Leerink.

Basma

Hi, good afternoon. Thank you for taking our question. This is Basma on for Marc. Could you please provide quick color on the launch on our — on the BTC performance in second half, the Ziihera in BTC in the second half of the year? And also, we just have a quick question on Epidiolex. Can you remind us, if you did collect cognitive data in the different DEs[Phonetic] such as LGS and DS and Dravet? That’s it for us. Thank you.

Bruce Cozadd

I think in light of the limited remaining time, we’ll just answer the first question, which Renee, maybe we’ll come to you on the BTC launch.

Renee Gala

Sure. So I would say keep in mind that BTC represents a very small patient population. And as we’ve said, while this is very important for us to make this medicine available for patients, we do expect the revenue contribution to be modest. We don’t provide guidance by-product. So I’m not going to give specific expectations for the second half. But I would say what we’re hearing from HCPs is they’re really pleased to have the product available. They’re having a positive experience with the drug. And for us, we’re really looking forward to seeing the GEA data late in the fourth quarter.

Basma

Thank you.

Operator

This concludes the question-and-answer session. I would now like to turn it back to Bruce Cozadd for closing remarks.

Bruce Cozadd

All right. Thank you, operator. And I’d like to close today’s call by recognizing our Jazz colleagues for their efforts and thank our partners and shareholders for their continued confidence and support. And as I said earlier in the call, it’s been a pleasure working with many of you for a few years, a lot of years, a decade, two decades or three decades depending on who I’m talking to, and you’re in very good hands with the continuing Jazz team. So good afternoon, everyone.

Operator

[Operator Closing Remarks]