Jazz Pharmaceuticals plc (JAZZ) Q2 2022 Earnings Report, Transcript and Summary

Ladies and gentlemen, and thank you for standing by. Welcome to the Second Quarter 2022 Jazz Pharmaceuticals Earnings 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] I would now like to turn the call over to your host Andrea Flynn, Vice President and Head-Investor Relations. You may begin.

Thank you and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2022 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Cozadd, Chairman, and Chief Executive Officer; Renée Galá, Executive Vice President and Chief Financial Officer; Dan Swisher, President; and Rob Iannone, Executive Vice President, Global Head of R&D. Kim Sablich, Executive Vice President and General Manager, North America will join the team for Q&A. On slide 2, I’ll remind you that today’s webcast includes forward-looking statements such as those related to our future financial and operating results, including expectations related to Vision 2025 and our guidance for 2022, growth potential and anticipated development and commercialization milestones and goals, 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 the statements contained in today’s press release, in our slide deck, and in our latest SEC disclosure document, which identify 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. Turning to slide 3, on this webcast, we’ll discuss non-GAAP financial measures. Reconciliations of GAAP to non-GAAP financial measures are included in today’s press release and in the slide presentation available on the Investors section of our website. I’ll now turn the call over to Bruce.

Thank you, Andrea. Good afternoon, everyone, and thank you for joining us today. I'll start on slide 5. We entered 2022 with substantial momentum, and our team has continued to make notable advances across our business through the first half of the year, while delivering solid year-over-year top and bottom line growth in the first and second quarters. Our productive second quarter reflects meaningful progress towards achieving Vision 2025, which we introduced at the beginning of the year. We're pleased with our results in the first half of the year and are confident that we are on track to achieve our full year 2022 guidance. Starting with our commercial business, our oxybate franchise is performing well, and we remain confident in the durability of Xywav, which we believe will be the oxybate therapy of choice in the market even following the entry of higher sodium authorized generics and potentially branded competition. We are pleased to see continued Xywav adoption in narcolepsy and are equally excited about the positive momentum of the launch of Xywav in idiopathic hypersomnia, or IH. There are a growing number of IH patients on Xywav therapy and a high level of engagement and receptivity in the market, all of which is underpinned by strong reimbursement. Turning to Epidiolex. We continue to expand our prescriber base and are generating real-world evidence and data to further substantiate Epidiolex's broad effect across seizure types. Our team has done an excellent job of launching the product ex-US, and we remain confident we can achieve blockbuster status for Epidyolex. Zepzelca remains the treatment of choice in second-line small cell lung cancer, and our robust development effort is aimed at identifying additional patient populations who may benefit from therapy. Rylaze continued its strong launch, and we are pleased to be able to deliver the only therapy available to patients in the US who experience a hypersensitivity reaction to E. coli-derived asparaginase. Dan will provide a detailed overview of our performance across our commercial portfolio later in the call. Our R&D team has remained very productive in the first half of 2022 and advancing multiple clinical programs. In addition, we were pleased that FDA cleared the IND application for JZP-815, allowing this program to enter clinical development. As we highlighted on our last earnings call, we completed in-licensing deals to add two new early-stage molecules to our pipeline in the second quarter, including JZP441, a potent, highly selective orexin-2 agonist that has the potential to advance the treatment of narcolepsy and other sleep disorders. And JZP898, a differentiated conditionally activated interferon alpha INDUKINE molecule with the potential to minimize the toxicity associated with systemic interferon alpha therapy, thereby, expanding its clinical utility in treating cancer. These transactions demonstrate our commitment to expanding our pipeline and diversifying our revenue. Consistent with these objectives, we are prioritizing the medicines and R&D programs most likely to deliver value to patients and shareholders. I'm also pleased to share that we've achieved our deleveraging target two quarters ahead of our stated time line, finishing the second quarter with a non-GAAP net leverage ratio of 3.2. The current macro environment is creating attractive options for corporate development, and our strong balance sheet provides us with flexibility to be active in identifying additional opportunities. Turning to slide 6. Vision 2025 provides us with a clear road map as we transform our business and includes three components central to driving sustainable growth and enhanced value; commercial, pipeline and operational excellence. Starting with commercial. After achieving over $3 billion in revenue in 2021, we're positioned to grow revenue to $5 billion in 2025 through a combination of existing products, as well as potential new therapies emerging from our pipeline and through corporate development. Our R&D organization continues to advance key programs, addressing significant patient needs in neuroscience and oncology. And we anticipate delivering at least five novel product approvals by the end of the decade through a combination of existing pipeline programs and corporate development. And on operational excellence, our 2021 adjusted operating margin was 43%, and we plan to improve that by five percentage points from 2021 to 2025, delivering more of our top line through to the bottom line. I'll now turn the call over to Dan for an overview of our second quarter commercial performance, after which Rob will share an update on the progress of our R&D programs. Renée will provide a financial overview, and then we'll open the call to Q&A. Dan?

Thanks, Bruce. I'm encouraged by the progress we have made across our commercial portfolio in the second quarter. Starting with neuroscience on slide 8, we are maintaining positive momentum in our oxybate franchise, continuing the robust launch in IH and driving adoption of Xywav in narcolepsy. With Xywav, we have meaningfully advanced patient care with a lower sodium oxybate product. The breadth of our Xywav development efforts was recently highlighted by our presence in June at SLEEP 2022, the 36th Annual Meeting of the Associated Professional Sleep Society. We and our partners debuted new data from 17 abstracts across narcolepsy and IH. It was a well-attended in-person event, providing the opportunity to connect with customers and KOLs to gain valuable insights into their experience with Xywav in both narcolepsy and IH, and we came away very encouraged by their feedback. In the second quarter, average active oxybate patients increased to approximately 17,100, an increase of nearly 8% compared to the same period last year. In Xywav for narcolepsy, we continue to see strong performance in the second quarter. Our efforts around educating physicians and patients about the lifelong burden of high sodium intake are resonating, and we exited the second quarter with approximately 7,550 narcolepsy patients taking Xywav. Looking ahead, we expect to see additional adoption of Xywav from existing Xyrem patients and importantly, the large majority of new to oxybate narcolepsy patients are beginning their therapy with Xywav. For Xywav and IH, we remain encouraged by the continued robust launch momentum and positive feedback from prescribers and the IH community. Actually, in the second quarter, there were approximately 1,150 IH patients taking Xyway. We continue to focus on educating prescribers and patients about the compelling efficacy and established safety profile of the first and only FDA-approved therapy for IH, and we are confident in our ability to maximize Xywav's potential in this underserved market. We've achieved our goal of obtaining similar coverage to narcolepsy with approximately 90% of commercial lives covered. We're pleased that payers have recognized the value that IH patients can realize from initiating Xywav therapy. Patients find our comprehensive and customized support valuable, and we expect that educational efforts for prescribers and patients will increase the awareness building this market over time. Stepping back, in each of the last four quarters, our commercial and medical education initiatives around Xywav have translated into growth of approximately 900 active patients per quarter across both indications. And we achieved a significant milestone in the second quarter with more active oxybate patients taking Xywav than Xyrem. We have an integrated field sales team that is supporting both narcolepsy and IH across a concentrated call universe with significant overlap among narcolepsy and IH prescribers. Coupled with orphan drug exclusivity for both indications that extends to 2027 for narcolepsy and 2028 for IH as well as Orange Book-listed patents that extend out to 2033, we believe Xywav is well positioned to be a durable product and one of our core growth drivers. Now turning to Slide 9 and Epidiolex. Net product sales grew by 12% in the second quarter of 2022, compared to the same period last year on a pro forma basis as we continue to add Epidiolex prescribers. As we have previously highlighted, we expect that as new prescribers gain experience with Epidiolex and see its clinical utility, they will more broadly adopt Epidiolex as a cornerstone therapy for their treatment-resistant patients. We are also committed to continuing to generate clinical study data and real world evidence to further support the utility of Epidiolex across a broad range of difficult to treat seizure types. Our commercial team continues to focus on more in-person engagement. This is a promotionally sensitive market, and we are encouraged that our field sales force has experienced increased access to physician offices and treatment centers in recent months. And we're seeing continued adoption and growth ex US. We remain on track to gain reimbursement for Epidyolex in France this year, at which point, Epidyolex will be launched and reimbursed in all five major European markets. We also have opportunity for additional growth coming from a total of 10 anticipated new markets and indication launches throughout this year. Given Epidiolex's unique mechanism of action, efficacy and safety profile and ability to be combined with other therapies, we are confident we can achieve a blockbuster status for Epidiolex as a global standard of care in treatment-resistant epilepsies. Now moving to oncology and starting with Zepzelca on slide 10. Second quarter net product sales were $68.3 million. As Bruce highlighted, we have rapidly established Zepzelca as the treatment of choice in second-line small cell lung cancer. To support our efforts to further grow market share in our current indication, we are investing in additional real-world evidence in observational studies. We believe these data will add to the body of evidence around Zepzelca's positive benefit risk profile for second-line small cell lung cancer patients and support increased adoption moving forward. Also, our robust development plan, which Rob will cover in more depth has the potential to identify additional patient populations who could benefit from this therapy, including treatment of first-line small cell lung cancer and other tumor types, providing the opportunity for meaningful future growth. Turning to slide 11. Second quarter net product sales for Rylaze, or recombinant erwinia asparaginase therapy, were $73 million. Rylaze's demand reflects increased brand awareness among customers and its position in the market as the only therapy available to patients in the US, who have a hypersensitivity reaction to E. coli derived asparaginase. Customer feedback continues to be positive, and prescribers have indicated they are now returning to best clinical practice switching to non-E. coli derived asparaginase earlier when there has been an initial hypersensitivity reaction observed. This is driven by the product profile, reliable supply of Rylaze and the suite of support services that we provide. Looking ahead, the potential label updates in the US to a Monday, Wednesday, Friday dosing schedule and IV administration has the potential to improve the Rylaze experience for clinicians and patients. We've also completed our Marketing Authorization Application or MAA submission to the European Medicines Agency with potential for approval in 2023. Now, I will turn the call over to Rob to provide an R&D update. Rob?

Thanks, Dan. Slide 13 provides an overview of our R&D pipeline. Looking across the pipeline, we are advancing a number of programs. Within neuroscience, we plan to initiate the Phase 3 trial for Epidiolex in epilepsy with myoclonic atonic seizures shortly. This would add a potential fourth indication to our label and provide the first clinical data on a fourth seizure type, myoclonic atonic seizures. We're also planning to initiate a pivotal Phase 3 trial for Epidiolex in Japan this year that would include Dravet, LGS and TSC. In addition, enrollment in our trials for suvecaltamide and JZP150 is ongoing. With respect to our nabiximols program, we announced top line results from the Phase III RELEASE MSS 1 trial in June. The trial did not meet the primary endpoint of change in Lower Limb Muscle Tone-6 between baseline and day 21, as measured by the Modified Ashworth Scale. The goal of RELEASE MSS1 was to have an early look at the effect of nabiximols in patients with MS spasticity, and we continue to assess the trial results. In terms of safety, the profile was consistent with previously reported adverse events with no new safety signals attributable to nabiximol. Moving to oncology. As Dan mentioned, we are advancing a robust development effort for Zepzelca for the treatment of lung cancer. This includes an ongoing Phase III trial supported by Jazz and our partner, Roche, to evaluate Zepzelca in combination with Tecentriq in first-line extensive-stage small cell lung cancer, a confirmatory Phase III trial in second-line small cell lung cancer being run by our partner, PharmaMar, and our own post-marketing observational trial in second-line small cell lung cancer. We recently presented data from four poster presentations at the ASCO Annual Meeting, evaluating Zepzelca in a range of small cell lung cancer settings. We're also exploring Zepzelca and other solid tumors with the initiation of our Phase II basket trial called EMERGE-201 earlier this year. This is a multicenter open-label trial designed to assess the safety and efficacy of Zepzelca as monotherapy in three cohorts of patients with solid tumors, advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and HRD tumors that have progressed following a platinum-containing regimen. Turning to Rylaze. In the second quarter, we completed an MAA submission to the European Medicines Agency, which included Monday, Wednesday, Friday and every 48-hour dosing schedules as well as IV and IM administration. This followed our submission of a supplemental BLA for Rylaze in the US to update our label to a Monday, Wednesday, Friday dosing schedule with patients receiving 25 milligrams per meter squared on Monday and Wednesday and 50 milligrams per meter squared on Friday. The schedule, which is more in line with current clinical practice to avoid weekend dosing would allow patients to maintain a clinically meaningful level of serum asparaginase activity through the entire duration of treatment. Currently, the label dosing schedule is every 48 hours at 25 milligrams per meter squared. Clinical data using Monday, Wednesday, Friday dosing were presented at the recent ASCO Annual Meeting. We also completed a separate sBLA to support intravenous dosing. Similar to the review of our original BLA, both on Monday, Wednesday, Friday IM dosing schedule and IV formulation sBLAs are being reviewed under the real-time oncology review process. In line with our anticipation of multiple INDs through 2023, FDA recently cleared the IND application for JZP815, our pan-RAF inhibitor for the treatment of solid tumors that continue with patients in the MAP kinase pathway, which will allow the product to enter clinical development. At the annual AACR meeting in April, we presented preclinical data demonstrating that JZP815 selectively and potently inhibits mutant A, B and C RAF kinases and also demonstrated robust antitumor activity in the RAS- and BRAF-mutated tumor RAF models. Now I will pass the call off to Renee for our financial update. Renee? Renée Galá: Thanks, Rob. I'll begin on Slide 15. Our impressive second quarter financial results demonstrate our progress so far in 2022. We achieved strong top and bottom line growth with second quarter total revenues of $933 million, representing growth of 24% compared to the same quarter in 2021. This included neuroscience net product sales of $697 million and oncology net product sales of $230 million, representing growth of 20% and 40%, respectively, compared to the second quarter of 2021. Importantly, we are on track to meet our 2022 total revenue guidance of $3.5 billion to $3.7 billion. With respect to operating expenses, we continue to focus on strategic, disciplined use of capital and expect to come in towards the lower end of our full year OpEx guidance ranges. Our continued focus on both the top and bottom line drove second quarter adjusted net income of $305 million, a 27% increase compared to the same period in 2021. Adjusted EPS was $4.30 in the second quarter, a 10% increase compared to the same period last year. Excluding the accounting change for convertible debt on a like-for-like basis, adjusted EPS growth would have been 23% compared to the same period in 2021. Based on the results from the first half of the year and our projections for the remainder of the year, we anticipate coming in towards the upper end of our 2022 non-GAAP ANI guidance range of $1.18 billion to $1.25 billion. In summary, we're very pleased with our performance year-to-date. We are affirming our non-GAAP adjusted guidance and have updated our GAAP guidance, primarily to reflect the impact of foreign currency exchange movements on non-US dollar-denominated amortization and inventory step-up expense. Turning to Slide 16. We committed to rapid deleveraging following the GW transaction, and I am pleased to report that we have achieved our goal of a net leverage ratio of less than 3.5 on a non-GAAP basis, two quarters ahead of our stated time line. Our non-GAAP net leverage ratio was approximately 3.2 at the end of the second quarter. This achievement has been underpinned by our disciplined capital allocation, focusing on both the top and bottom line as well as our continued strong cash generation. Having achieved our deleveraging target, our focus will continue to be on managing the balance sheet through disciplined capital allocation and leveraging our strong cash flow, which provides us with meaningful flexibility for further corporate development initiatives. Corporate development is a foundational pillar of our strategy to deliver long-term growth and value for both patients and shareholders and is important to our efforts o achieve Vision 2025. Consistent with that, our corporate development efforts remain focused on diversifying and enhancing our product portfolio and pipeline, leveraging our unique insights in commercial infrastructure and strengthening the overall sustainability of our business. With our strategic investments, expanding product portfolio and focus on operational excellence, we believe we are well positioned to achieve Vision 2025 and deliver further diversification, sustainable growth and enhanced value to patients and shareholders. I will now turn the call back to Bruce for final remarks.

Thanks, Renee. I'll conclude our prepared remarks on Slide 18. We're pleased to be building on the strong momentum we have created over the previous quarters across commercial, R&D and corporate development despite a challenging period in the biotech sector and global markets in general. In our commercial efforts, we are focused on execution across our neuroscience and oncology portfolios, including maximizing the Xywav in IH and Rylaze launches, realizing the blockbuster potential of Epidiolex and continuing to drive adoption of Xywav in narcolepsy and Zepzelca in small cell lung cancer. Our R&D team is advancing multiple mid- and late-stage programs, and we expect to submit several INDs through 2023. Operational excellence also remains a key area of focus, including maximizing our adjusted operating margin while making strategic investments for future growth. In summary, we remain on track to achieve Vision 2025 and the affirmation of our top and bottom line guidance for 2022 underscores the confidence we have in our strategy and execution across the business. That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

[Operator Instructions] Our first question comes from Jessica Fye with JPMorgan. Your line is open.

Hey, guys. Good afternoon. Thanks for taking my question. Now that you've exceeded your net leverage target early, should we think of that as unlocking potentially larger business development transactions sooner than 2023?

Thanks for the question, Jess. Really pleased to have achieved this target so quickly through both paydown of some debt but also continued growth in our profitability. Maybe for implications of this, I'll turn it over to Renée for a couple of comments. Renée Galá: Yes. Thanks, Bruce, and thanks for the question. So agree, yes, this does provide us with greater flexibility with respect to corporate development. As Bruce mentioned, the focus not just on paying down debt, but also increasing, enhancing our EBITDA gives us greater flexibility because dollar for dollar, we're getting more out of that net leverage ratio by improving the EBITDA. And going forward, it also gives us greater capacity as we look at future targets. We've stated in the past and today on the call that we expect corporate development to be an important pillar for us going forward, both on the commercial front and then also on the pipeline. So we're excited to be well positioned to continue to execute on that front.

Thank you. One moment for our next question. Our next question comes from Marc Goodman with SVB Leerink. Your line is open.

Yes, hi. Can you talk a little bit about how these patients that are -- with the 11 50. Are the naive patients to oxybate? Are they -- have they used oxybate or these other products? Just give us a sense of who these patients are and what they're doing? Are they being dosed once a night, or are they being dosed twice a night? And then just you didn't update the time line on the nabiximols next study, if you could just do that. Thanks.

Yes, Marc, let's start with your IH question. We've said we're very excited to enter this segment where there's been no FDA-approved treatment. We know people have tried things off label historically, primarily daytime stimulants, the way promoting agents despite their relatively small impact on disease. We also know that historically, there was some attempt to use oxybate to treat IH but payer restrictions made that fairly uncommon. Maybe I'll ask Kim to update you a little bit on how the launch is going from a patient acquisition perspective. And any comments she wants to make on the dose, and then Rob can chime in to answer your nabiximols question. Kim?

Sure, Bruce. Yes, we continue to be very pleased with the uptake of this product, the first and only FDA-approved treatment for IH, so we're really encouraged by the robust launch momentum and really, especially by the feedback that we're getting from prescribers who have actually utilized Xywav in their idiopathic hypersomnia patient population. Our focus today remains in addition to sharing the safety and efficacy profile of Xywav in idiopathic hypersomnia. We're also focused on continuing as we did prior to launch to educate prescribers and patients about the disease itself and IH, and particularly ensuring they understand the full breadth of symptoms, not just excessive daytime sleepiness. We're also happy that Dan shared to be at a place as we had planned. We are now 90% of commercial lives are covered for idiopathic -- plan, we are now 90% of commercial lives are covered for idiopathic hypersomnia. And I've been pleased with our customers are telling us that this offering is meeting their needs, both in terms of the product and the support services that we're offering.

Thanks. [Operator Instructions]

There was a follow-up question for Marc, just on the timing of the two ongoing the nabiximols study. So Marc, as you know, when we last updated on this, we were experiencing some, I would say, not unexpected challenges in getting those trials up and running related to some logistical issues -- sorry, the ongoing pandemic, and we're working through those. We have some mitigations that we're putting into place. But we don't yet have a firmer time line on those two trials at this time.

[Operator Instructions] Our next question is from Ken Cacciatore with Cowen. Your line is open.

Hey, team, great performance. I want to just drill down a little bit more on the IH launch. We're asked often this is bolus that we're seeing or warehouse patients. Can -- maybe Bruce or Kim, can you talk about are we seeing normal demand? And to what degree do we think the pace that we've been observing will be consistent or not consistent going forward? And can you talk about to the degree in which the sales force is marketing versus still focused on narcolepsy conversion? Is this something where the sales force is indeed marketing aggressively, or are we still kind of at a lower level than we'll have as we go forward? And then just lastly, any early view on patient retention? I know it's very early days, but any thoughts on that? Thanks so much.

Yes, Ken, thanks for the questions. I'll start and then ask Kim to jump in. We don't think there was any bolus or warehousing of patients in any significant way. It's certainly true that there were some KOLs out there that were waiting for the launch of the product, have seen the strong Phase III clinical data. Obviously, saw our approval. You know that our actual launch post-state are approval by a little bit while we completed REMS implementation. So there certainly was some starting point for getting patients on the therapy, but we don't think of that as a bolus in the way you're suggesting it. In terms of the pace of adding patients, I'd just like to remind you, we're only a couple of quarters into this launch. So probably a little too early for a lot of super accurate trending. As Dan said in his remarks during the script, we're just really pleased to be seeing growth in narcolepsy patients, whether that's patients coming over from Xyrem, or patients new to oxybate therapy, including newly diagnosed narcolepsy patients or whether they're IH patients getting the benefit of Xywav for the treatment of idiopathic hypersomnia. We're seeing really strong growth in the overall Xywav franchise. Maybe Kim could comment on how she and the team are balancing our efforts across narcolepsy and IH, and whether that will change in the future and can add any comments on retention that she'd like.

Sure, Bruce. So I think as we've shared before, this is a very efficient launch for us and that it's largely the same base of customers. There's 90% overlap between those ACPs that we're calling on for narcolepsy and IH. And really, to your question, Ken, of how we're balancing that, it is a balancing act. But I can say that we are out there fully supporting both the continued transitions and new patient starts from narcolepsy as well as the launch of IH. And our teams know that, first and foremost, we've got to keep the momentum going on narcolepsy, but I can say that we've got a very strong full effort for both. In terms of patient retention, I don't think we've shared specific numbers, but I would just instead comment on more of the qualitative feedback that we've gotten from HCPs in terms of them being very pleased with the product and that they see that its performance when their patients is consistent with what they saw in the clinical studies.

Thank you. One moment for our next question. Our next question comes from Jason Gerberry with Bank of America. Your line is open.

Hey, guys. Thanks for taking the question. I wanted to just drill in on Epidiolex. If you can talk a little bit about these enhanced marketing efforts? Is this going to be more of a second half-driven benefit? And as we think about the performance this quarter, just curious, are we seeing meaningful first-time contribution ex U.S. as with the US growth is perhaps even lower than what was the overall reported number? Just wondering if you could help us sort of figure out like what's going on now and some of the marketing initiatives as we think about second half? Thanks.

Yes. Dan, maybe I could ask you to jump in on Epidiolex just globally, including the rollout ex US in recent quarters.

Sure. Yes. No, we're -- I mean, we're very pleased to see the growth and continue to hear great feedback from the increase in prescriber base in the US and the persistence remains strong. We said this in the past that it is a promotionally sensitive product. And importantly, our field force is increasing the level of face-to-face engagement, which is really important, especially for the smaller offices and the prescribers who haven't had experience or much experience with Epidiolex to move it more broadly into their treatment-resistant epilepsy. Regarding the ex US, we don't break out the sales, but it has -- we always view it as a meaningful growth driver to the overall franchise as a global brand. I did reference that we've got 10 new market and indication launches. A couple of them have already gone with Norway and Ireland, successful to plan, six indication launches, and we've still got a number of countries pending, especially France, which would be the last of the big countries. So yes, so we're very confident about achieving ultimately the blockbuster status as a cornerstone of treatment-resistant epilepsy.

Thank you. One moment for the next question. Our next question comes from Brandon Folkes with Cantor. Your line is open.

Hi, thanks for taking my question and congratulations on a good quarter. Can you maybe just talk about the competitive dynamics you're seeing for new patients start within narcolepsy. It was a strong quarter on your part from new patient adds, it looks like. We saw a competitor was to report strong new patient adds. So can you just elaborate a little bit on the market? Is this just sort of a normal step-up post the 1Q headwinds thrown in with -- we had Omnicon earlier this year, or is there maybe just a bit more of a durable interest in the branded narcolepsy space, given you have two branded competitors after promoting agents? And maybe just any commentary on it in terms of getting in front of physicians in person. Thank you.

Yes, Brandon, I would say we couldn't be more happy with the continued growth of Xywav in narcolepsy as well as in IH over these past quarters. So just the number of patients on therapy is very gratifying. We think some of that is because we've come along with a truly differentiated -- a better product due to the low sodium with FDAs orphan drug exclusivity, finding clinical superiority on the basis of safety because of this very large reduction in nightly sodium intake in a chronic disease where we know this patient population is at significant risk of cardiovascular comorbidities. We've really got something that I think is attracting both former Xyrem patients, but also potentially new patients. It is generally true that oxybate patients are on -- not in all cases, but generally true, but they are on other agents. Often, our agent is taken at night, and there are other daytime agents they're taking. And I think that the product you're referring to pitolisant falls into that category of a daytime treatment that's also been adding new patients. So patients experiment with combinations that make sense for them. But we've continued to see the kind of excellent growth we've really wanted to see, again, across existing oxybate patients and new oxybate patients.

Thank you. One moment for our next question. Our next question comes from David Amsellem with Piper Sandler. Your line is open.

Hey, thanks. I wanted to drill down a little more about IH. And I apologize if I missed this, but in terms of IH, are these patients new diagnoses who are now getting treatment, or are these patients who have already been on wakefulness promoting agents like modafinil? And then as a corollary to that question, do you think that with the availability of Xywav, you're going to -- you're seeing more diagnoses in general? Can you comment on that as well? Thanks.

Yes. David, maybe I'll start with a broad picture and then let Kim go to our more current strategy. Broadly, we do think the availability of the first-ever approved -- FDA-approved agent in IH may well spur more diagnosis going forward. It's often the case when there's a reward for diagnosis and that it unlocks a treatment option and it unlocks reimbursement for a treatment option, you'll see doctors move all the way through that diagnosis where otherwise they might not. But in terms of our current strategy for penetrating the IH space, maybe I'll let Kim make a few remarks.

Yes, sure. So we've got a really nice size market of diagnosed patients to go after, and we're focusing our initial launch. I think as we said several times, not only on an existing sleep call universe, but also on the 37,000 adult patients who already not only have a formal diagnosis of idiopathic hypersomnia, but we're also in the health care system, we can see actively seeking health care. So that's why our strategy is really much more focused on encouraging HCPs to get appropriate patients started on Xywav. And we really have a three-pronged approach out there in the marketplace right now. As I mentioned earlier, we're continuing our efforts to improve general understanding of the disease of idiopathic hypersomnia, particularly that relates to the breadth of patient symptoms experience given that we have a very broad indication in this condition. We're also educating on the compelling efficacy and safety profile. And we're helping HCPs identify those patients in their practice who are already diagnosed who may be ready for Xywav. They've had many, many years to figure out what that oxybate patient in narcolepsy looks like they're just getting started in the case of idiopathic hypersomnia. So those are really the three key areas that we're focusing on in large population that's already diagnosed.

Thank you. One moment for our next question. Our next question comes from Jeff Hung, Sir, your line is open.

Thanks for taking my question. You've indicated for multiple quarters that you're adding new prescribers for Epidiolex. Can you talk more about the new US prescribers? And do they tend to translate to multiple prescriptions fairly rapidly? And have those dynamics changed much over time? Thanks.

Kim, maybe I'll hand that over to you in terms of who the new Epidiolex prescribers are and what that means to our business.

Yes, sure. The newer prescribers, I can really just say the characteristic is that there are obviously slower adopters as you see in any marketplace. And we do believe the key is to getting in there face-to-face, educating them on the product profile and getting them to start using the product because what we see -- from the beginning of the launch until now is that once a new prescriber gains experience with Epidiolex and is able to see first hand its clinical utility, they more broadly adopt Epidiolex as a cornerstone therapy for their treatment-resistant patients. What I'd say is one of the approaches that we've been taking pretty much since the beginning of the year, with HCPs who don't have experience with Epidiolex or we believe are underutilizing it in their practice, is we're leveraging the fact that this is a category that naturally utilizes polypharmacy. And we're highlighting data that we have on the synergistic effect of using Epidiolex in combination with clobazam. Clobazam is a product that's already on board in the vast majority of patients. And we have found that by sharing these data with these HCPs that have yet to utilize Epidiolex at all or robustly is that they've been highly impressed with the data as they demonstrate an ability to reduce the number of seizures in both LGS and Dravet syndrome by more than 60%, which is a number -- an efficacy number that a very uncommon outcome and they recognize this the moment we share that data. So it's a very promotionally sensitive market. We're encouraged that our sales force has had increased access to offices and treatment centers in recent months, and we're really confident that our level of promotion is going to continue to increase in the second half of the year, and we've got a strong set of data. I just had to move those slower adopters into trying Epidiolex.

Thank you. One moment for our next question. Our next question comes from Gary Nachman with BMO. Your line is open.

Thanks. Good afternoon. So Rylaze was really strong in 2Q. Any unusual stocking in there in the quarter? Does that all reflect demand? You mentioned that docs are switching patients back earlier if they have a reaction to asparaginase. So could you expand on that dynamic? And how should we think about that run rate from here, especially if you get Monday, Wednesday, Friday dosing? .

Yes, Gary, thanks for the question. We could not be more pleased with where we are. Just a couple of quarters into the Rylaze launch and how quickly we think physicians have moved to the best possible treatment paradigm for these ALL patients. Kim, maybe I'll let you answer as to whether there was any unusual stocking and how we think about this run rate for Rylaze.

No, I don't think we saw anything unusual going on this quarter. I think current utilization in the US is outperforming. If you look at the numbers, the peak that we experienced with Erwinia, reinforcing the impact that supply constraints had on providing optimal patient care. And we think that really the demand trend we're seeing reflects not only the increased brand awareness and familiarity of Rylaze with customers and its position in the market as the only available therapy right now for patients who have a hypersensitivity reaction to E. coli-derived asparaginase. But really at this point, we think a lot of it has to do with the things that Dan highlighted in terms of we see customers who had put in place asparaginase sparing activities such as desensitization and rechallenge practices are now telling us and we're seeing through ordering patterns that they are stopping those practices and they're starting to utilize Rylaze instead. So all the very positive signals that the market is excited about Rylaze and ready to get back to optimal practices.

And Kim, just to add on, this is Dan. We do have global rights to the product. And as we updated on the call, we did complete our submission to the EMA in the second quarter. Market dynamics are a little different there. Erwinia is on the market. But again, we think with our fully recombinant and easier to administer and already in a formulation but also importantly, we studied it into an updated 25, 25, 50 dosing schedule that optimizes asparaginase levels through patients. So we look forward to that being on the market in 2023 in Europe. And then we're assessing other marketplaces, including Japan.

Thank you. One moment for our next question. Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open.

Hi, everyone. Thanks for taking our questions. I want to follow up on some of the earlier discussion around Epidiolex. And I guess kind we're ultimately, I think, curious about is to what extent do you see further growth in Epidiolex? Is it around geographic expansion, indication expansion are kind of just like expansion of the onboard prescribers use of the drug kind of up the lines of risk of epilepsy?

Dan, do you want to take global opportunity for Epidiolex and where we see that going in the future?

Yes, sure. I mean I'd say yes to everything you just referenced. I mean there's plenty of headroom in the current indications as we think about the combination with clobazam. Clobazam is much more broadly used right now than Epidiolex. And we do have continued data generation across different seizure types as well as sharing real-world evidence from the medical records. And then importantly, ex US, we're at 14 of 34 countries in terms of launches. France, just pending this year and opportunity for us to move more broadly into Asia as well. So we're super excited by what this brand can do long term. It's cornerstone unique mechanism, very combinable, and we've seen, for example, with clobazam enhanced antiseizure activity, which is always sort of the critical factor for these patients.

Thank you. One moment for our next question. Our next question comes from Ami Fadia with Needham. Your line is open.

Good evening. Thanks for taking my question. Going back to idiopathic hypersomnia, can you give us some more color around the market dynamics? Where are these patients coming from in terms of who are the subscribers. Are they existing Xyrem or Xywav prescribers for narcolepsy? And if you could give us some color on what percent of your existing prescribers for narcolepsy have prescribed a patient for IH? And also give us a sense of the patient journey, especially given the fact that there haven't been other treatments for IH available in the market, so how often are these patients going back to the physician, seeking treatment or something new? That would be helpful. Thank you.

Yes. Kim, do you want to provide any additional information on overlap of prescribing positions and maybe pattern of when patients see their physicians?

Yes. I don't believe we have that data to share, Bruce. Maybe somebody can let me know, if they feel otherwise. But in terms of how frequently patients are seeing their doctor, we see that typically out there in the marketplace, what we hear is the idiopathic hypersomnia visit their doctor twice a year. Really, the main statistics that we have about the HCP population is that in terms of potential and where the IH patients are receiving treatment, there's 90% overlap in terms of where the patients reside and which HCP offices, but I don't have data at this time in terms of what percentage of physicians have prescribed for both IH and narcolepsy.

Thank you. One moment for our next question. Our next question comes from Gregory Renza with RBC. Your line is open.

Great. Thanks, Bruce and team for taking my question and congrats on the quarter. Bruce, I just wanted to touch back again just one more on Epidiolex. I'm just curious, just in the context of the competitive landscape with respect to developmental therapies, I'm just curious if you could comment a bit on Epidiolex, maybe longer term, just given there have been some positive developments and some setbacks amongst the landscape of late. You certainly commented on combination and cycling, but any added thoughts as that landscape even evolved would be great. Thank you very much.

Yes, I would just remind people that the conditions we're treating with Epidiolex are very severe epilepsies, very treatment refractory and patients have often tried a number of therapies before they get to Epidiolex. Of course, we've seen benefit and a good safety profile with Epidiolex, so that as patients, their families and physicians continue to seek both better seizure control and just overall better results for their child. They tend to stay on Epidiolex even if they might rotate off or try a different therapy. I've personally heartened that there are continued developments that might offer additional relief to these patients, give them more things to put in the armamentarium of agents to try, but we haven't seen anything yet on the horizon that strikes us as reducing the opportunity for Epidiolex. I think we may see benefits of combined treatment, much like you heard touch on in Kim's comments about clobazam a little bit earlier. So lots of room for improvements on current results from these patients and some of our evidence generation and additional trials is to continue to bring out that benefit, whether that's in another seizure type like EMAS or whether that's just better elucidating what we are seeing in patients treated with Epidiolex. Rob, maybe I could ask you to jump in just from a physician perspective about treatment of these trials at onset seizure disorders and how you see that going forward?

Sure, happy to, Bruce. So it's clear that Epidiolex has been very effective in these groups of highly refractory epilepsy, both in terms of seizure reduction, and other measures around seizure frequency, free days, for example, but also in terms of but well-being. Last year's AES, we showed a caretaker survey where there's clearly benefits observed outside of just measures of epilepsy itself, so becoming a cornerstone for therapy. And as you mentioned, the safety profile allows for combining with other therapies. So at the moment, physicians, practitioners continue to have a lot of enthusiasm about it. And to the extent that there are new drugs coming into these spaces, probably thinking about it more in terms of another add-on to be combined rather than to replace in what's a pretty highly refractory set of conditions.

Operator, I think we probably have time for one more question.

Our last question comes from Ashwani Verma with UBS.

Sorry, I was going to ask like on nabiximols, anything that you can share from the Phase III, this RELEASE MSS1 trial? I understand that you didn't see statistically significant benefit, but did you see directional benefit?

Yes. Rob, do you want to jump in on data from the recent top line unblinded nabiximols trial?

We haven't given further details on that, and we certainly are combing through the data in greater detail to understand what we can learn from this and how that might ultimately impact the rest of the program, if it does at all. Nothing more to add at this time.

Yes. And Ash, I'll just remind you that this is not the first trial ever none with nabiximols, so we're looking back across all trials with the agent as well as our ongoing trials to chart the best course forward.

So with that, maybe we'll wrap up the call, and I'll thank everyone for joining us. We're really excited about the upcoming opportunities across our business as we continue to drive growth and shareholder value. We remain on track and focused on achieving Vision 2025. And as always, I'd love to close today's call by recognizing all of our Jazz colleagues for their commitment to delivering new therapeutic options. I thank our partners and our shareholders for their continued confidence and support. Thank you all for joining us today.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.