Suvecaltamide

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

– Total revenues of $3.8 billion in 2023 and $1 billion in 4Q23 – – 27% year-over-year revenue increase from combined key growth drivers: Xywav®, Epidiolex® and Rylaze® – – Oncology revenue surpassed $1 billion in 2023 – – Multiple late-stage pipeline catalysts anticipated in 2024 – – 2024 total revenue guidance reflects continued top-line growth – DUBLIN, Feb. 28, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced financial results for the full year and fourth quarter of 2023 and provided guidance for 2024. "2023 was a year of continued strong execution that delivered top- and bottom-line growth and over $3.8 billion in total revenue. Sleep1 revenue exceeded $1.9 billion, Oncology revenue surpassed $1 billion and Epidiolex remains on track to deliver on its blockbuster potential, demonstrating our progress towards Vision 2025 targets. We also meaningfully advanced our late-stage pipeline and are pleased to note enrollment of the Phase 3 Zepzelca® trial in first-line small cell lung cancer has been completed," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "Looking to 2024, we expect double-digit percentage revenue growth across combined key growth drivers: Xywav, Epidiolex and Rylaze. We look forward to multiple near-term, late-stage pipeline catalysts and anticipate completing the rolling BLA submission for zanidatamab in second-line biliary tract cancer in the first half of 2024. We expect our disciplined capital allocation to enable investment in our key commercial growth drivers for near-term growth, in our pipeline for long-term growth and to provide flexibility for corporate development." Key Highlights Achieved first $1 billion revenue quarter. Key growth drivers: Xywav net product sales grew 33% year-over-year; annualizing2 at $1.35 billion. Epidiolex/Epidyolex® net product sales grew 15% year-over-year; annualizing2 at over $900 million. Rylaze net product sales grew 40% year-over-year; annualizing2 at over $400 million. Initiated zanidatamab 1L BTC confirmatory trial in 1Q24. Multiple near-term, late-stage pipeline catalysts anticipated: Completion of rolling BLA submission for accelerated approval in 2L BTC in 1H24. Top-line PFS data from zanidatamab in Phase 3 1L GEA targeted for late 2024. 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 data from Zepzelca 1L SCLC Phase 3 trial at the end of 2024 or early 2025. The Company will host a virtual zanidatamab R&D Day on Tuesday, March 19, 2024. 2024 total revenue guidance of $4.0 to $4.2 billion, 7% top-line growth at the mid-point. Total revenue guidance is underpinned by expectations of continued growth in net sales of Xywav in IH, Epidiolex/Epidyolex, our Oncology therapeutic area, and royalties on net sales of authorized generics of Xyrem® offset by a continued decline in net sales of Xyrem. Business Updates Key Commercial Products Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution: Xywav net product sales increased 33% to $1,273.0 million in 2023 and increased 20% to $337.0 million in 4Q23 compared to the same periods in 2022. As the only low-sodium oxybate and the only therapy approved to treat IH, expect Xywav to remain the oxybate of choice. There were approximately 12,300 active Xywav patients exiting 4Q23. Results from the real-world TENOR study were published in Sleep Medicine. The most common reason cited for switching to Xywav was long-term health benefits due to lower sodium content of Xywav. A review of scientific evidence was published in Neurology and Therapy showing oxybate regimens impart substantial and highly similar medical benefit on subjective and objective measures of sleep and daytime function regardless of dosing. Xywav for Narcolepsy: There were approximately 9,525 narcolepsy patients taking Xywav exiting 4Q23. Xywav for Idiopathic Hypersomnia (IH): There were approximately 2,775 IH patients taking Xywav exiting 4Q23. Xyrem (sodium oxybate) oral solution: Xyrem net product sales decreased 44% to $569.7 million in 2023 and decreased 57% to $106.7 million in 4Q23 compared to the same periods in 2022. High-Sodium Oxybate Authorized Generic (AG) Royalties: Royalties from high-sodium oxybate AGs were $75.9 million in 2023 and $39.4 million in 4Q23. The Company expects high-sodium oxybate AG royalty revenue to exceed $200 million in 2024, which reflects an increase in the fixed-rate royalty structures of the AG agreements in 2024. Epidiolex/ Epidyolex (cannabidiol): Epidiolex/Epidyolex net product sales increased 15% to $845.5 million in 2023 and increased 16% to $240.6 million in 4Q23 compared to the same periods in 2022. Outside of the U.S., Epidyolex is approved in more than 35 countries with additional launches and reimbursement anticipated through the end of 2024. Long-term and real-world data of treatment-resistant epilepsy were presented at AES 2023: Data from long-term Expanded Access Program study demonstrated Epidiolex was associated with a sustained reduction in treatment-resistant, focal-onset seizures through 144 weeks. Interim results from the BECOME-TSC survey of caregivers of patients with tuberous sclerosis complex (TSC) demonstrated improved day-to-day function, cognition, language and communication and emotional and social function in patients. Rylaze/ Enrylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze net product sales increased 40% to $394.2 million in 2023 and increased 26% to $101.7 million in 4Q23 compared to the same periods in 2022. Initiated European rolling launch of Enrylaze (JZP458; a recombinant Erwinia asparaginase or crisantaspase), marketed as Rylaze in the U.S. and Canada, in 4Q23. Zepzelca (lurbinectedin): Zepzelca net product sales increased 7% to $289.5 million in 2023 and increased 3% to $74.0 million in 4Q23 compared to the same periods in 2022. 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, is complete; expect top-line progression-free survival (PFS) data readout at the end of 2024 or early 2025. Key Pipeline Highlights Zanidatamab: Initiated the zanidatamab rolling biologics license application (BLA) submission in 4Q23 for accelerated approval in second-line (2L) biliary tract cancer (BTC) and expect to complete the rolling submission 1H24. Initiated confirmatory trial in 1L metastatic BTC, where there remains unmet patient need, in 1Q24. 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 increased enrollment in the trial from 714 to 918 to improve statistical power for overall survival analysis, while maintaining PFS top-line readout. Data presented at SABCS in heavily pretreated patients with HER2+/HR+ metastatic breast cancer demonstrated 67% PFS at six months with a median PFS of 12 months. In addition to achieving clinically meaningful improvements, data presented at the ASCO Gastrointestinal Cancers Symposium in January 2024 demonstrated that patients who responded to zanidatamab also reported improved quality of life with less pain interference in the Phase 2b HERIZON-BTC-01 trial. Suvecaltamide (JZP385): Patient enrollment is ongoing in the Phase 2b essential tremor (ET) trial; top-line data readout is anticipated late 1H24. A Phase 2 trial in patients with Parkinson's disease tremor is ongoing. JZP898: Initiated a Phase 1 first-in-human clinical trial in solid tumors in 4Q23. Corporate Development KRAS Inhibitor Program Agreement: In February 2024, the Company acquired Redx Pharma's KRAS inhibitor program, which includes G12D selective and pan-KRAS molecules, further expanding Jazz's early-stage oncology pipeline. Ion Channel Targets Agreement: In November 2023, the Company and Autifony announced an exclusive global license and collaboration agreement to discover and develop drug candidates for two different ion channel targets associated with neurological disorders. Continued Repurchases under Previously Announced $1.5 Billion Share Repurchase Program The Company continued repurchases of its ordinary shares on the open market in the fourth quarter of 2023 as part of its previously authorized and announced share repurchase program. As of December 31, 2023, approximately $161 million remained available and authorized for share repurchases, after the purchase of approximately $100 million of shares during the fourth quarter of 2023. The timing and amount of repurchases under the program will depend on a variety of factors, including the price of the Company's ordinary shares, alternative investment opportunities, restrictions under the Company's credit agreement, corporate and regulatory requirements and market conditions. Financial Highlights GAAP net income for 2023 was $414.8 million, or $6.10 per diluted share, compared to a GAAP net loss of $(224.1) million, or $(3.58) per diluted share, for 2022. GAAP net income for 4Q23 was $94.2 million, or $1.42 per diluted share, compared to a GAAP net loss of $(240.7) million, or $(3.82) per diluted share, for 4Q22. Non-GAAP adjusted net income for 2023 was $1,295.8 million, or $18.29 per diluted share, compared to $933.6 million, or $13.20 per diluted share, for 2022. Non-GAAP adjusted net income for 4Q23 was $345.3 million, or $5.02 per diluted share, compared to a Non-GAAP adjusted net loss of $(4.2) million, or $(0.07) per diluted share, for 4Q22. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release. Total Revenues Total revenues increased 5% in 2023 and 4% in 4Q23 compared to the same periods in 2022. Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, of $2,783.8 million in 2023 and $728.9 million in 4Q23, was broadly in line with the same periods in 2022 and included increased Xywav and Epidiolex/Epidyolex net product sales, offset by decreased Xyrem revenues, reflecting the strong adoption of Xywav by existing Xyrem patients and the impact of high-sodium oxybate competition. High-sodium oxybate AG royalty revenue relates primarily to royalty revenue received from Hikma Pharmaceuticals plc on net sales of a high-sodium oxybate AG product. Oncology net product sales increased 16% in 2023 and 22% in 4Q23 compared to the same periods in 2022, primarily driven by the continued growth in Rylaze product sales, which increased 40% to $394.2 million in 2023 and increased 26% to $101.7 million in 4Q23 compared to the same periods in 2022. Operating Expenses and Effective Tax Rate Changes in operating expenses in 2023 and 4Q23 over the prior year periods are primarily due to the following: Cost of product sales decreased in 2023 and 4Q23 compared to the same periods in 2022, on a GAAP basis, primarily due to lower acquisition accounting inventory fair value step-up expense and the impact of an expense in 2022 for past royalties payable under a settlement agreement with Otsuka Pharmaceutical Co., Ltd, or the Otsuka past royalty expense, partially offset by changes in product mix. Cost of product sales, on a non-GAAP adjusted basis, increased in 2023 compared to the same period in 2022 primarily due to changes in product mix, partially offset by the Otsuka past royalty expense and decreased in 4Q23 compared to the same period in 2022 primarily due to the Otsuka past royalty expense, partially offset by changes in product mix. Selling, general and administrative (SG&A) expenses, on a GAAP basis, decreased in 2023 compared to the same period in 2022, primarily due to the loss on disposal of Sunosi, restructuring costs and GW related integration costs incurred in 2022, together with a reduction in costs related to program terminations, partially offset by an impairment of facility assets in 2023. SG&A expenses, on a GAAP and on a non-GAAP adjusted basis, in 2023 included lower compensation-related expenses compared to 2022. SG&A expenses, on a GAAP basis, increased in 4Q23 compared to the same period in 2022, primarily due to an impairment of facility assets in 4Q23, offset by costs related to program terminations incurred in 2022. SG&A expenses, on a GAAP and on a non-GAAP adjusted basis, in 4Q23 included lower compensation-related and litigation expenses compared to 4Q22. Research and development (R&D) expenses increased in 2023 and 4Q23 compared to the same periods in 2022, on a GAAP and on a non-GAAP adjusted basis, primarily due to the inclusion of costs related to zanidatamab, as well as our other key pipeline programs. Acquired IPR&D expense in 4Q23 and 2023, on a GAAP and on a non-GAAP adjusted basis, primarily related to an upfront payment made in connection with our licensing and collaboration agreement with Autifony Therapeutics Limited. Acquired IPR&D expense in 4Q22, on a GAAP and on a non-GAAP adjusted basis, related to payments of $375.0 million to Zymeworks Inc., in connection with our licensing and collaboration agreement. Acquired IPR&D expense in 2022, on a GAAP and on a non-GAAP adjusted basis, also included upfront payments of $50.0 million to Sumitomo Pharma Co., Ltd in relation to our licensing agreement and $15.0 million to Werewolf Therapeutics, Inc., in connection with our licensing and collaboration agreement. The intangible asset impairment charge in 2022, on a GAAP basis, related to the discontinuation of our nabiximols program. Cash Flow and Balance Sheet As of December 31, 2023, cash, cash equivalents and investments were $1.6 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 year ended December 31, 2023, the Company generated $1,092.0 million of cash from operations reflecting strong business performance and continued financial discipline. 2024 Financial Guidance Jazz Pharmaceutical's full year 2024 financial guidance is 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. GMT) to provide a business and financial update and discuss its 2023 full year and 4Q23 results and 2024 guidance. Audio webcast/conference call: U.S. Dial-In Number: +1 888 350 4423 Ireland Dial-In Number: +353 1800 943 926 Additional global dial-in numbers are available here. Passcode: 6907242 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; the Company's expectations for total revenue and Oncology revenue growth in 2024 and anticipated product sales; expectations of continued growth in net sales of Xywav, Epidiolex/Epidyolex and the oncology portfolio; the blockbuster potential of Epidiolex/Epidyolex and its significant additional growth opportunities; the Company's expectations to executing multiple Epidyolex launches through 2024; expectations with respect to royalties from AGs; the Company's ability to achieve Vision 2025 and the Company's progress related thereto; the Company's development, regulatory and commercialization strategy; the Company's advancement of pipeline programs and the timing of development activities, regulatory activities and submissions related thereto, including the ability to deliver multiple late-stage data readouts by the end of 2025, expectations to complete a rolling BLA submission for zanidatamab for BTC in the first half of 2024 and top line data from a Phase 3 trial of Epidyolex for Dravet syndrome, Lennox-Gastaut syndrome and TSC in Japan in the second half of 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; expectations that Xywav will remain the oxybate of choice; the Company's capital allocation and corporate development strategy; the potential successful future development, manufacturing, regulatory and commercialization activities; the Company's expectation of meaningful growth as part of its Vision 2025; growing and diversifying the Company's revenue, investing in its pipeline of novel therapies, and delivering innovative therapies for patients and the potential benefits of such therapies; 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; planned or anticipated clinical trial events, including with respect to initiations, enrollment and data read-outs, and the anticipated timing thereof; 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; the timing and amount of repurchases of the Company's ordinary shares; 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; Epidiolex realizing its blockbuster potential; 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; restrictions on repurchases of capital stock; 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, 2022 as supplemented by its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, and future filings and reports by the Company including the Company's Annual Report on Form 10-K for the year ended December 31, 2023. 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 Logo -