Sodium Oxybate/Potassium Oxybate/Calcium Oxybate/Magnesium Oxybate

– 12% year-over-year revenue increase from combined key growth drivers: Xywav®, Epidiolex® and Rylaze® – – Oncology revenues grew 13% year-over-year – – Submitted zanidatamab BLA for 2L BTC; expect to launch in 2025 or earlier – – Top-line Phase 2b data from suvecaltamide trial in essential tremor expected in late 1H24 – – 2024 total revenue guidance affirmed at $4.0 to $4.2 billion – DUBLIN, May 1, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced financial results for the first quarter of 2024 and affirmed guidance for 2024. "In the first quarter of 2024, we delivered combined double-digit year-over-year growth from our key growth drivers: Xywav, Epidiolex and Rylaze. We also significantly advanced our zanidatamab program with the completion of the BLA for 2L BTC," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "We believe the robust growth in patients benefitting from Xywav underscores the appreciation physicians and patients have for the long-term health benefits of reducing sodium and expect Xywav to remain the oxybate of choice. We see continued demand for Rylaze as the only non-E. coli asparaginase regimen that provides sustained activity throughout the course of treatment, and we expect continued growth of Epidiolex to be driven by geographic expansion, optimized dosing and data demonstrating its beyond-seizure benefits. Growing and durable revenues from Xywav, Epidiolex and Rylaze, coupled with our pipeline progress, drive our confidence in delivering on our guidance and objectives for 2024." Key Highlights Key growth drivers: Xywav net product sales grew 14% year-over-year. Epidiolex/Epidyolex® net product sales grew 5% year-over-year. Rylaze/Enrylaze® net product sales grew 20% year-over-year. Zanidatamab: Completed the zanidatamab BLA submission seeking accelerated approval in 2L BTC. Updated data with longer follow-up, including overall survival (OS) findings, from the HERIZON-BTC-01 trial will be presented at ASCO Annual Meeting 2024. Plan to initiate Phase 3 EMPOWHER trial in late-line HER2+ breast cancer in 2H24. Multiple near-term, late-stage pipeline catalysts anticipated: Suvecaltamide top-line data from Phase 2b trial in ET in late 1H24. Top-line data from Epidyolex Phase 3 trial in Japan in 2H24. Top-line PFS data from zanidatamab in Phase 3 1L GEA targeted for late 2024. Top-line data from Zepzelca® 1L SCLC Phase 3 trial at the end of 2024 or early 2025. Affirmed 2024 total revenue guidance of $4.0 to $4.2 billion. Business Updates Key Commercial Products Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution: Xywav net product sales increased 14% to $315.3 million in 1Q24 compared to the same period in 2023. As the only low-sodium oxybate and the only therapy approved to treat idiopathic hypersomnia (IH), expect Xywav to remain the oxybate of choice. There were approximately 12,950 active Xywav patients exiting 1Q24, with 275 net patient adds in IH. Data presented at 2024 AAN Annual Meeting demonstrated the real-world impacts of Xywav: Results from the RHYTHM study demonstrated patients with IH experienced higher odds of comorbid conditions across multiple clinical categories, including cardiovascular conditions. A review of five clinical studies evaluating the impact of once- and twice-nightly oxybates on sleep quality, sleep architecture and measures of disrupted nighttime sleep in narcolepsy found oxybate was effective in improving these measures regardless of dosing. Xywav for Narcolepsy: There were approximately 9,900 narcolepsy patients taking Xywav exiting 1Q24. Xywav for Idiopathic Hypersomnia (IH): There were approximately 3,050 IH patients taking Xywav exiting 1Q24. Xyrem® (sodium oxybate) oral solution: Xyrem net product sales decreased 64% to $64.2 million in 1Q24 compared to the same period in 2023. High-Sodium Oxybate Authorized Generic (AG) Royalties: Royalties from high-sodium oxybate AGs were $49.9 million in 1Q24. The Company expects high-sodium oxybate AG royalty revenue to exceed $200 million in 2024. Epidiolex/ Epidyolex (cannabidiol): Epidiolex/Epidyolex net product sales increased 5% to $198.7 million in 1Q24 compared to the same period in 2023. Epidiolex/Epidyolex growth was negatively affected by inventory drawdown in 1Q24. Outside of the U.S., Epidyolex is approved in more than 35 countries with additional launches and reimbursements anticipated through the end of 2024. Long-term and real-world data of treatment-resistant epilepsy were presented at 2024 ANN Annual Meeting: Data from a long-term Expanded Access Program study demonstrated Epidiolex was associated with a sustained reduction in treatment-resistant, focal-onset seizures through 144 weeks, with an acceptable safety profile. Updated interim results of seizure and non-seizure outcomes from the BECOME-TSC survey of caregivers of patients with tuberous sclerosis complex (TSC) reported improvements in seizure frequency and severity and in cognition, language and communication in patients. Rylaze/ Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales increased 20% to $102.8 million in 1Q24 compared to the same period in 2023. Zepzelca (lurbinectedin): Zepzelca net product sales increased 12% to $75.1 million in 1Q24 compared to the same period in 2023. Enrollment in the Phase 3 trial evaluating first-line (1L) use of Zepzelca in combination with Tecentriq ® (atezolizumab) in small cell lung cancer, in partnership with Roche, was completed in 1Q24; expect top-line progression-free survival (PFS) data readout at the end of 2024 or early 2025. Key Pipeline Highlights Zanidatamab: Completed the zanidatamab biologics license application (BLA) seeking accelerated approval from the U.S. FDA for second-line (2L) biliary tract cancer (BTC). If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. The Company's plans to submit a marketing authorization application (MAA) to the European Medicines Agency (EMA) are proceeding. Updated data with longer follow-up, including OS findings, from the HERIZON-BTC-01 trial will be presented at the ASCO Annual Meeting 2024. A confirmatory trial in 1L metastatic BTC is ongoing. The pivotal HERIZON-GEA-01 trial, evaluating zanidatamab in 1L gastroesophageal adenocarcinoma (GEA), is ongoing and the Company is targeting top-line PFS data in late 2024. The Company plans to initiate a Phase 3 trial, EMPOWHER, in the second half of 2024 to evaluate zanidatamab plus chemotherapy or trastuzumab plus chemotherapy in patients with HER2-positive breast cancer whose disease has progressed on previous T-DXd treatment. Suvecaltamide (JZP385): Enrollment was completed in the Phase 2b essential tremor (ET) trial in 1Q24; top-line data readout is anticipated late 1H24. A Phase 2 trial in patients with Parkinson's disease tremor is ongoing. Financial Highlights GAAP net loss for 1Q24 was $(14.6) million, or $(0.23) per diluted share, compared to a GAAP net income of $69.4 million, or $1.04 per diluted share, for 1Q23. Non-GAAP adjusted net income for 1Q24 was $182.2 million, or $2.68 per diluted share, compared to a Non-GAAP adjusted net income of $285.3 million, or $3.95 per diluted share, for 1Q23. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release. Total Revenues Total revenues increased 1% in 1Q24 compared to the same period in 2023, driven by higher Oncology product sales of 13%, primarily due to continued growth in Rylaze/Enrylaze, which increased 20% to $102.8 million in 1Q24 compared to the same period in 2023, partially offset by lower neuroscience revenues. Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, of $630.9 million decreased in 1Q24 compared to the same period in 2023, primarily due to decreased Xyrem revenues, reflecting the adoption of Xywav by existing Xyrem patients, high-sodium oxybate competition and changes to formulary coverage, partially offset by increased royalty revenue received on net sales of high-sodium oxybate AG products and increased Xywav and Epidiolex/Epidyolex net product sales. Operating Expenses and Effective Tax Rate Changes in operating expenses in 1Q24 over the prior year period are primarily due to the following: Cost of product sales, on a GAAP basis, decreased in 1Q24 compared to the same period in 2023, primarily due to lower acquisition accounting inventory fair value step-up expense. Cost of product sales, on a non-GAAP adjusted basis, in 1Q24 was in line with the same period in 2023. Selling, general and administrative (SG&A) expenses increased in 1Q24 compared to the same period in 2023, on a GAAP and on a non-GAAP adjusted basis, primarily due to increased compensation-related expenses driven by higher headcount in support of our key growth drivers, investment in our priority programs and litigation costs. Research and development (R&D) expenses increased in 1Q24 compared to the same period in 2023, on a GAAP and on a non-GAAP adjusted basis, primarily due to higher costs related to zanidatamab, as well as our other key pipeline programs, and an increase in compensation-related expenses driven by higher headcount in support of our development programs. Acquired in-process research and development (IPR&D) expense in 1Q24, on a GAAP and on a non-GAAP adjusted basis, related to an upfront payment made in connection with our asset purchase and collaboration agreement with Redx Pharma plc. Cash Flow and Balance Sheet As of March 31, 2024, cash, cash equivalents and investments were $1.8 billion, and the outstanding principal balance of the Company's long-term debt was $5.8 billion. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $500.0 million. For the three months ended March 31, 2024, the Company generated $267.2 million of cash from operations reflecting strong business performance and continued financial discipline. 2024 Financial Guidance The Company is affirming its full year 2024 financial guidance as follows: Conference Call Details Jazz Pharmaceuticals will host an investor conference call and live audio webcast today at 4:30 p.m. ET (9:30 p.m. IST) to provide a business and financial update and discuss its 2024 first quarter results. Audio webcast/conference call: U.S. Dial-In Number: +1 800 715 9871 Ireland Dial-In Number: +353 1800 943 926 Additional global dial-in numbers are available here. Passcode: 8991966 Interested parties may access the live audio webcast via the Investors section of the Jazz Pharmaceuticals website at . To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website at . About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit for more information. Non-GAAP Financial Measures To supplement Jazz Pharmaceuticals' financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), the Company uses certain non-GAAP (also referred to as adjusted or non-GAAP adjusted) financial measures in this press release and the accompanying tables. In particular, the Company presents non-GAAP adjusted net income (and the related per share measure) and its line item components, as well as certain non-GAAP adjusted financial measures derived therefrom, including non-GAAP adjusted gross margin percentage and non-GAAP adjusted effective tax rate. Non-GAAP adjusted net income (and the related per share measure) and its line item components exclude from GAAP reported net income (loss) (and the related per share measure) and its line item components certain items, as detailed in the reconciliation tables that follow, and in the case of non-GAAP adjusted net income (and the related per share measure), adjust for the income tax effect of the non-GAAP adjustments. In this regard, the components of non-GAAP adjusted net income, including non-GAAP adjusted cost of product sales, SG&A expenses and R&D expenses, are income statement line items prepared on the same basis as, and therefore components of, the overall non-GAAP adjusted net income measure. The Company believes that each of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors and analysts and that each of these non-GAAP financial measures, when considered together with the Company's financial information prepared in accordance with GAAP, can enhance investors' and analysts' ability to meaningfully compare the Company's results from period to period, to its forward-looking guidance, and to identify operating trends in the Company's business. In addition, these non-GAAP financial measures are regularly used by investors and analysts to model and track the Company's financial performance. Jazz Pharmaceuticals' management also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate the Company's business and to make operating decisions, and compensation of executives is based in part on certain of these non-GAAP financial measures. Because these non-GAAP financial measures are important internal measurements for Jazz Pharmaceuticals' management, the Company also believes that these non-GAAP financial measures are useful to investors and analysts since these measures allow for greater transparency with respect to key financial metrics the Company uses in assessing its own operating performance and making operating decisions. These non-GAAP financial measures are not meant to be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with the Company's consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles in the reconciliation tables that follow. In addition, from time to time in the future there may be other items that the Company may exclude for purposes of its non-GAAP financial measures; and the Company has ceased, and may in the future cease, to exclude items that it has historically excluded for purposes of its non-GAAP financial measures. Likewise, the Company may determine to modify the nature of its adjustments to arrive at its non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measures as used by Jazz Pharmaceuticals in this press release and the accompanying tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. Caution Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to: the Company's growth prospects and future financial and operating results, including the Company's 2024 financial guidance and the Company's expectations related thereto and anticipated catalysts; expectations that Xywav will remain the oxybate of choice; expectations of high-sodium oxybate AG royalty revenue in 2024; the future growth and durability of revenues; the Company's advancement of pipeline programs and the timing of development activities, regulatory activities and submissions related thereto; planned or anticipated clinical trial events, including with respect to initiations, enrollment and data read-outs, and the anticipated timing thereof, including expectations of a potential launch of zanidatamab in 2L BTC in 2025 or earlier, top line data from a Phase 2b trial of suvecaltamide in ET, initiating a Phase 3 trial of zanidatamab plus chemotherapy or trastuzumab plus chemotherapy in patients with HER2-positive breast cancer whose disease has progressed on previous T-DXd treatment, top line PFS data from a Phase 3 trial of zanidatamab in 1L GEA, top line data from a Phase 3 trial of Epidyolex in DS, LGS and TSC in Japan and top line PFS data from a Phase 3 trial of Zepzelca in 1L SCLC; and the Company's development, regulatory and commercialization strategy, including the Company's expectations to executing multiple Epidyolex launches through 2024; the Company's expectations with respect to its products and product candidates and the potential of the Company's products and product candidates and the potential regulatory path related thereto; the Company's capital allocation and corporate development strategy; the potential successful future development, manufacturing, regulatory and commercialization activities; the Company's ability to realize the commercial potential of its products; the Company's net product sales and goals for net product sales from new and acquired products; the Company's views and expectations relating to its patent portfolio, including with respect to expected patent protection, as well as expectations with respect to exclusivity; the Company's clinical trials confirming clinical benefit or enabling regulatory submissions; planned or anticipated regulatory submissions and filings, and the anticipated timing thereof; potential regulatory approvals; and other statements that are not historical facts. These forward-looking statements are based on the Company's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward- looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: maintaining or increasing sales of, and revenue from, Xywav, Rylaze and Epidiolex/Epidyolex and other marketed products; the introduction of new products into the U.S. market that compete with, or otherwise disrupt the market for the Company's products and product candidates; effectively launching and commercializing the Company's other products and product candidates; the successful completion of development and regulatory activities with respect to the Company's product candidates, obtaining and maintaining adequate coverage and reimbursement for the Company's products; the time-consuming and uncertain regulatory approval process, including the risk that the Company's current and/or planned regulatory submissions may not be submitted, accepted or approved by applicable regulatory authorities in a timely manner or at all; the costly and time-consuming pharmaceutical product development and the uncertainty of clinical success, including risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients; global economic, financial, and healthcare system disruptions and the current and potential future negative impacts to the Company's business operations and financial results; geopolitical events, including the conflict between Russia and Ukraine and related sanctions; macroeconomic conditions, including global financial markets, rising interest rates and inflation and recent and potential banking disruptions; regulatory initiatives and changes in tax laws; market volatility; protecting and enhancing the Company's intellectual property rights and the Company's commercial success being dependent upon the Company obtaining, maintaining and defending intellectual property protection and exclusivity for its products and product candidates; delays or problems in the supply or manufacture of the Company's products and product candidates; complying with applicable U.S. and non-U.S. regulatory requirements, including those governing the research, development, manufacturing and distribution of controlled substances; government investigations, legal proceedings and other actions; identifying and consummating corporate development transactions, financing these transactions and successfully integrating acquired product candidates, products and businesses; the Company's ability to realize the anticipated benefits of its corporate development transactions and its collaborations and license agreements with third parties; the sufficiency of the Company's cash flows and capital resources; the Company's ability to achieve targeted or expected future financial performance and results and the uncertainty of future tax, accounting and other provisions and estimates; the Company's ability to meet its projected long-term goals and objectives, including as part of Vision 2025, in the time periods that the Company anticipates, or at all, and the inherent uncertainty and significant judgments and assumptions underlying the Company's long-term goals and objectives; fluctuations in the market price and trading volume of the Company's ordinary shares; the timing and availability of alternative investment opportunities; and other risks and uncertainties affecting the Company, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports, including the Company's Annual Report on Form 10-K for the year ended December 31, 2023, as supplemented by our Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and future filings and reports by the Company. Other risks and uncertainties of which the Company is not currently aware may also affect the Company's forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. Contacts: Investors: Andrea N. Flynn, Ph.D. Vice President, Head, Investor Relations Jazz Pharmaceuticals plc [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 Media: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 SOURCE Jazz Pharmaceuticals plc

Two oral presentations share results of real-world impact of idiopathic hypersomnia and long-term effectiveness of Epidiolex® (cannabidiol) in treatment-resistant epilepsies Thirteen abstracts underscore Jazz's diverse neuroscience portfolio and pioneering efforts to continue advancing the treatment of serious sleep disorders, rare epilepsy syndromes and movement disorders DUBLIN, April 10, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that 13 abstracts from across its neuroscience portfolio and pipeline, including two oral presentations, will be featured at the 76th Annual American Academy of Neurology Meeting (AAN) being held April 13-18, 2024, in Denver. Two encore datasets were selected for oral presentations, including results from a real-world claims analysis that demonstrated the increased risk of comorbid conditions, such as stroke or cardiovascular disease, in individuals living with idiopathic hypersomnia compared to those without the condition. Additional data being presented include a post-hoc analysis from the Epidiolex® (cannabidiol) oral solution Expanded Access Program (EAP) that explores the long-term effectiveness of Epidiolex on reduction of treatment-resistant focal-onset seizures. "Jazz's presentations at the 2024 AAN Annual Meeting reflect our leadership in sleep and rare epilepsies, as well as our commitment to developing therapies for debilitating, and often overlooked, neurological disorders," said Rob Iannone, MD, MSCE, executive vice president and global head of research and development of Jazz Pharmaceuticals. "We remain committed to expanding our knowledge of the patient experience, including the real-world impact and effectiveness of our products, in order to achieve our purpose of transforming the lives of patients and their families." Highlights at the 2024 AAN Annual Meeting include: An oral presentation showcasing results from the Real-World Idiopathic Hypersomnia Total Health Model (RHYTHM) study which, using claims data, compared the comorbid conditions of individuals diagnosed with idiopathic hypersomnia with those experienced by individuals without idiopathic hypersomnia. Results revealed that individuals with idiopathic hypersomnia experienced higher odds of comorbid conditions across multiple clinical categories, including cardiovascular conditions, reaffirming the importance of considering the patient's full clinical profile when evaluating treatment options for patients living with idiopathic hypersomnia. A second oral presentation focusing on a post-hoc analysis that examined the real-world outcomes and long-term effectiveness of Epidiolex in treatment-resistant focal-onset seizures in individuals who participated in the EAP. Findings showed that Epidiolex was associated with a reduction in focal seizures through 144 weeks, with an acceptable safety profile. Two posters assessing the impact of Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution, the first and only low-sodium oxybate, on sleep inertia in individuals living with idiopathic hypersomnia, including results from a Phase 3 trial. One poster reporting the final results from the SEGUE study of adults with narcolepsy transitioning from Xyrem® (sodium oxybate) oral solution, a high-sodium oxybate, to Xywav, showing that participants switched from high-sodium to low-sodium oxybate with minimal adjustments to their dosing. A poster reviewing key data from five clinical studies evaluating the impact of all once- and twice-nightly high-sodium oxybates on sleep quality, sleep architecture and measures of disrupted nighttime sleep in narcolepsy. The review found that oxybate was effective in improving measures of sleep architecture and disrupted nighttime sleep in patients with narcolepsy. Xyrem is indicated for the treatment of cataplexy and/or excessive daytime sleepiness (EDS) in narcolepsy patients. Five posters examining real-world treatment patterns, effectiveness and caregiver experiences with Epidiolex. Notable presentations include updated interim results of seizure and non-seizure outcomes from the cross-sectional BEhavior, COgnition, and More with Epidiolex (BECOME) tuberous sclerosis complex (TSC) caregiver survey, where the majority of caregivers reported improvements in patient seizure and non-seizure outcomes, including cognition, emotional and communication domains. Additionally, a post-hoc analysis demonstrated long term effectiveness of Epidiolex across all focal seizure subtypes in patients with TSC in GWPCARE6 Open Label Extension trial. Two posters featuring Jazz's research with investigational suvecaltamide (also known as JZP385) in essential tremor (ET) and Parkinson's disease (PD) tremor. Presentations include insights from a systematic review of existing literature on the epidemiology and treatment patterns of patients with ET, emphasizing the need for additional research in the space, and a study design overview of the ongoing Phase 2, proof-of-concept study evaluating the efficacy and safety of suvecaltamide on the functional impact of tremor in PD. The 2024 AAN Annual Meeting abstracts are available online at . A full list of Jazz-sponsored presentations follows: About Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution Xywav is a low-sodium oxybate approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. The Office of Orphan Product Development (OOPD) at the FDA also published its summary of clinical superiority findings for Xywav for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy by means of greater cardiovascular safety compared to Xyrem® (sodium oxybate) oral solution. The decision of the OOPD is based on the FDA findings that Xywav provides a greatly reduced chronic sodium burden compared to Xyrem. Xywav has 131 mg of sodium at the maximum recommended nightly dose. Xywav is comprised of a unique composition of cations resulting in 92% less sodium, or a reduction of approximately 1,000 to 1,500 mg/night. Xywav is the only low-sodium oxybate therapy approved by the FDA, and the only oxybate that does not carry a warning in the label related to use in patients sensitive to high sodium intake. Xywav is also the first and only U.S. FDA-approved treatment option for idiopathic hypersomnia in adults. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of idiopathic hypersomnia in adults. Xywav is the only FDA-approved treatment studied across the multiple symptoms of idiopathic hypersomnia, such as EDS, sleep inertia (severe grogginess or confusion when waking up), long sleep duration and cognitive impairment. Xywav can be administered as a twice- or once-nightly regimen for the treatment of idiopathic hypersomnia in adults. The exact mechanism of action of Xywav in the treatment of adults with idiopathic hypersomnia and of cataplexy and EDS in narcolepsy is unknown. It is hypothesized that the therapeutic effects of Xywav are mediated through GABAB actions during sleep at noradrenergic and dopaminergic neurons, as well as thalamocortical neurons.1 The U.S. Drug Enforcement Agency (DEA) has designated Xywav as a Schedule III medicine. The DEA defines Schedule III drugs, substances, or chemicals as drugs with a moderate to low potential for physical and psychological dependence.1,2 Because of the risks of central nervous system (CNS) depression and abuse and misuse, Xywav is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS. Important Safety Information for Xywav WARNING: Taking XYWAV with other central nervous system (CNS) depressants such as medicines used to make you or your child fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol, or street drugs, may cause serious medical problems, including trouble breathing (respiratory depression), low blood pressure (hypotension), changes in alertness (drowsiness), fainting (syncope), and death. The active ingredient of XYWAV is a form of gamma hydroxybutyrate (GHB). Abuse or misuse of illegal GHB alone or with other drugs that cause changes in alertness (or consciousness) has caused serious side effects. These effects include seizures, trouble breathing (respiratory depression), changes in alertness (drowsiness), coma, and death. Call your doctor right away if you or your child has any of these serious side effects. Because of these risks, you have to go through the XYWAV and XYREM REMS to have your or your child's prescription for XYWAV filled. Do not take XYWAV if you take or your child takes other sleep medicines or sedatives (medicines that cause sleepiness), drinks alcohol, or has a rare problem called succinic semialdehyde dehydrogenase deficiency. Keep XYWAV in a safe place to prevent abuse and misuse. Selling or giving away XYWAV may harm others and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Anyone who takes XYWAV should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane, for at least 6 hours after taking XYWAV. Those activities should not be done until you know how XYWAV affects you or your child. XYWAV can cause serious side effects, including the following: Breathing problems, including slower breathing, trouble breathing, and/or short periods of not breathing while sleeping (sleep apnea). People who already have breathing or lung problems have a higher chance of having breathing problems when they use XYWAV. Mental health problems, including confusion, seeing or hearing things that are not real (hallucinations), unusual or disturbing thoughts (abnormal thinking), feeling anxious or upset, depression, thoughts of killing yourself or trying to kill yourself, increased tiredness, feelings of guilt or worthlessness, or difficulty concentrating. Tell your doctor if you or your child have or had depression or have tried to harm yourself or themselves. Call your doctor right away if you have or your child has symptoms of mental health problems or a change in weight or appetite. Sleepwalking. XYWAV can cause sleepwalking, which can cause injuries. Call your doctor if this occurs. The most common side effects of XYWAV in adults include nausea, headache, dizziness, anxiety, insomnia, decreased appetite, excessive sweating (hyperhidrosis), vomiting, diarrhea, dry mouth, parasomnia (a sleep disorder that can include abnormal dreams, abnormal rapid eye movement (REM) sleep, sleep paralysis, sleep talking, sleep terror, sleep-related eating disorder, sleep walking, and other abnormal sleep-related events), somnolence, fatigue, and tremor. The most common side effects of XYREM (which also contains oxybate like XYWAV) in children include nausea, bedwetting, vomiting, headache, weight decrease, decreased appetite, dizziness, and sleepwalking. XYWAV can cause physical dependence and craving for the medicine when it is not taken as directed. These are not all the possible side effects of XYWAV. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please see full Prescribing Information, including Boxed Warning, here: About Xyrem® (sodium oxybate) Xyrem oral solution, CIII, is a product approved by the U.S. Food and Drug Administration (FDA) for both cataplexy and excessive daytime sleepiness in narcolepsy in adult and pediatric patients ages 7 and older.3 Xyrem may only be dispensed to patients enrolled in the XYWAV and XYREM REMS. Xyrem was first approved in the U.S. in 2002, based on clinical trial data in adults. Important Safety Information for Xyrem WARNING: Taking XYREM with other CNS depressants such as medicines used to make you or your child fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol, or street drugs, may cause serious medical problems, including trouble breathing (respiratory depression), low blood pressure (hypotension), changes in alertness (drowsiness), dizziness (syncope), and death. XYREM is a form of gamma hydroxybutyrate (GHB). Abuse or misuse of illegal GHB alone or with other drugs that cause changes in alertness (or consciousness) has caused serious side effects. These effects include seizures, trouble breathing (respiratory depression), changes in alertness (drowsiness), coma, and death. Because of these risks, you have to go through the XYWAV and XYREM REMS to have your or your child's prescription for XYREM filled. Do not take XYREM if you take or your child takes other sleep medicines or sedatives (medicines that cause sleepiness), drink alcohol, or have a rare problem called succinic semialdehyde dehydrogenase deficiency. Keep XYREM in a safe place to prevent abuse and misuse. Selling or giving away XYREM may harm others and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Anyone who takes XYREM should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane, for at least 6 hours after taking XYREM. Those activities should not be done until you know how XYREM affects you or your child. XYREM can cause serious side effects, including the following: Breathing problems, including slower breathing, trouble breathing, and/or short periods of not breathing while sleeping (sleep apnea). People who already have breathing or lung problems have a higher chance of having breathing problems when they use XYREM. Mental health problems, including confusion, seeing or hearing things that are not real (hallucinations), unusual or disturbing thoughts (abnormal thinking), feeling anxious or upset, depression, or thoughts of killing yourself or trying to kill yourself. Tell your doctor if you or your child have or had depression or have tried to harm yourself. Call your doctor right away if you have or your child has symptoms of mental health problems. Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you or your child starts sleepwalking. Your doctor should check you or your child. Tell your doctor if you are or your child is on a salt-restricted diet or if you have or your child has high blood pressure, heart failure, or kidney problems. XYREM contains a lot of sodium (salt) and may not be right for you or your child. The most common side effects of XYREM include nausea, sleepiness, dizziness, vomiting, bedwetting, and tremor (in adults). In pediatric patients, headache, decreased appetite, and weight decrease were also common. Your side effects may increase when you take higher doses of XYREM. XYREM can cause physical dependence and craving for the medicine when it is not taken as directed. These are not all the possible side effects of XYREM. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please find full prescribing information here: About Epidiolex®/Epidyolex® (cannabidiol) Epidiolex/Epidyolex is a prescription, plant-derived cannabis-based medicine administered as an oral solution which contains highly purified cannabidiol (CBD). Cannabidiol, the active ingredient in Epidiolex, is a cannabinoid that naturally occurs in the Cannabis sativa L. plant. The precise mechanisms by which EPIDIOLEX exerts its anticonvulsant effect in humans are unknown. Epidiolex was approved by the U.S. Food and Drug Administration (FDA) for use in the U.S., the European Commission (EC) for use in Europe, the Medicines and Healthcare products Regulatory Agency (MHRA) for use in Great Britain, the Therapeutic Goods Administration for use in Australia, Swissmedic for use in Switzerland, the Food & Nutrition Services of the Israel Ministry of Health for use in Israel, and the New Zealand Medicines and Medical Devices Safety Authority for use in New Zealand, is an oral solution which contains highly purified cannabidiol (CBD). In the U.S., Epidiolex is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) or tuberous sclerosis complex (TSC) in patients one year of age and older. Epidiolex has received approval in the European Union under the tradename Epidyolex for adjunctive use in conjunction with clobazam to treat seizures associated with LGS and DS in patients two years and older, and for adjunctive use to treat seizures associated with TSC, in patients two years of age and older. Epidiolex has received Orphan Drug Designation (ODD) from the U.S. FDA for the treatment of seizures associated with LGS, DS, and TSC. Similarly, Epidyolex received ODD from the European Medicines Agency (EMA) for the same indications. Important Safety Information & Indications CONTRAINDICATION: HYPERSENSITIVITY EPIDIOLEX (cannabidiol) oral solution is contraindicated in patients with a history of hypersensitivity to cannabidiol or any ingredients in the product. WARNINGS & PRECAUTIONS Hepatic Injury: EPIDIOLEX can cause dose-related transaminase elevations. Concomitant use of valproate and elevated transaminase levels at baseline increase this risk. Obtain transaminase and bilirubin levels prior to starting treatment, at 1, 3, and 6 months after initiation of treatment, and periodically thereafter, or as clinically indicated. Resolution of transaminase elevations occurred with discontinuation of EPIDIOLEX, reduction of EPIDIOLEX and/or concomitant valproate, or without dose reduction. For patients with elevated transaminase levels, consider dose reduction or discontinuation of EPIDIOLEX or concomitant medications known to affect the liver (e.g., valproate or clobazam). Dose adjustment and slower dose titration is recommended in patients with moderate or severe hepatic impairment. Consider not initiating EPIDIOLEX in patients with evidence of significant liver injury. There have been postmarketing reports of cholestatic or mixed patterns of liver injury. Elevated ammonia levels were reported in some patients with transaminase elevations; most taking concomitant valproate, clobazam, or both. Consider discontinuation or dose adjustment of valproate or clobazam if ammonia is elevated. Somnolence and Sedation: EPIDIOLEX can cause somnolence and sedation that generally occurs early in treatment and may diminish over time; these effects occur more commonly in patients using clobazam and may be potentiated by other CNS depressants. Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including EPIDIOLEX, increase the risk of suicidal thoughts or behavior. Inform patients, caregivers, and families of the risk and advise them to monitor and report any signs of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior. If these symptoms occur, consider if they are related to the AED or the underlying illness. Withdrawal of Antiepileptic Drugs: As with most AEDs, EPIDIOLEX should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. ADVERSE REACTIONS: The most common adverse reactions in patients receiving EPIDIOLEX (≥10% and greater than placebo) include transaminase elevations; somnolence; decreased appetite; diarrhea; pyrexia; vomiting; fatigue, malaise, and asthenia; rash; insomnia, sleep disorder and poor-quality sleep; and infections. Hematologic abnormalities were also observed. PREGNANCY: EPIDIOLEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Encourage women who are taking EPIDIOLEX during pregnancy to enroll in the EPIDIOLEX Pregnancy Surveillance Program and the North American Antiepileptic Drug (NAAED) Pregnancy Registry. DRUG INTERACTIONS: Strong inducers of CYP3A4 and CYP2C19 may affect EPIDIOLEX exposure. EPIDIOLEX may affect exposure to CYP2C19 substrates (e.g., clobazam, diazepam, stiripentol), orally administered P-gp substrates, or other substrates (see full Prescribing Information). Consider dose reduction of orally administered everolimus, with appropriate therapeutic drug monitoring, when everolimus is combined with EPIDIOLEX. A lower starting dose of everolimus is recommended when added to EPIDIOLEX therapy. Concomitant use of EPIDIOLEX and valproate increases the incidence of liver enzyme elevations. Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and clobazam. Dosage adjustment of EPIDIOLEX or other concomitant medications may be necessary. INDICATIONS: EPIDIOLEX (cannabidiol) oral solution is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older. Please read the EPIDIOLEX full Prescribing Information for additional important information here . About Jazz Pharmaceuticals plc Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit for more information. Caution Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to advancing the treatment of serious sleep disorders, rare epilepsy syndromes and movement disorders and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with pharmaceutical product development, and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2023, and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Media Contact: Kristin Bhavnani Head of Global Strategic Brand Engagement Jazz Pharmaceuticals plc [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Investors: Andrea N. Flynn, Ph.D. Vice President, Head, Investor Relations Jazz Pharmaceuticals plc [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 References: Xywav (calcium, magnesium, potassium and sodium oxybates) oral solution. Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2021. United States Drug Enforcement Agency. Drug Scheduling. . Accessed February 2024. Xyrem (sodium oxybate) oral solution. Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2022. SOURCE Jazz Pharmaceuticals plc