Sodium Oxybate

-- Generated $52.5 million in net revenue from sales of LUMRYZ™, a 93% increase over the first quarter of 2024 -- -- 2,800 patients on LUMRYZ as of March 31, 2025, a net increase of 300 patients since December 31, 2024 and a 100% year over year increase over the first quarter of 2024 -- -- Raises 2025 guidance; expects to generate $255 - $265 million in net product revenue and cash flow of $30 - $40 million, driven by 3,400 - 3,600 patients on LUMRYZ by year end -- -- Federal Circuit ruled in Avadel’s favor in appeal of Delaware Court injunction, allowing Avadel to seek and be granted FDA approval for LUMRYZ in Idiopathic Hypersomnia (IH) -- -- On track to complete enrollment in pivotal Phase 3 REVITALYZ™ study evaluating efficacy and safety of LUMRYZ in IH by the end of 2025 -- -- Avadel management to host a conference call today at 8:00 a.m. ET -- DUBLIN, May 07, 2025 (GLOBE NEWSWIRE) -- Avadel Pharmaceuticals plc (Nasdaq: AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, today announced its financial results for the first quarter ended March 31, 2025, and increased its 2025 financial guidance. “We are pleased with the strong progress achieved in the first quarter of 2025, as we have seen improvements across all patient demand metrics for LUMRYZ, including patient starts, persistency rates, and net patients on therapy. As a result, we are raising our full year 2025 guidance and expect $255 - $265 million in net revenue and 3,400 - 3,600 patients on therapy by year end,” said Greg Divis, Chief Executive Officer of Avadel Pharmaceuticals. “The improvements we are seeing are driven by the investments we made at the beginning of the year to expand our customer-facing teams, allowing us to deliver more personalized support and strengthen engagement with both patients and providers. We continue to build momentum and remain confident in our ability to deliver our growth plan and unlock the billion-dollar potential of LUMRYZ.” “In addition, yesterday’s favorable Federal Circuit decision allows Avadel to initiate new clinical trials, conduct open-label extension studies, and most importantly, pursue FDA approval for LUMRYZ’s use in idiopathic hypersomnia (“IH”) and additional indications. With enrollment in our pivotal Phase 3 trial in IH on track to complete before year end, we believe LUMRYZ is well positioned to unlock this meaningful market opportunity where, if approved, LUMRYZ’S extended-release, once-nightly dosing has the potential to offer even greater benefit than in narcolepsy, and we look forward to providing future updates.” First Quarter Highlights and 2025 Guidance: Generated $52.5 million of net product revenue from sales of LUMRYZ in the first quarter of 2025, representing 93% growth over the first quarter 2024.300 patients added during the quarter ended March 31, 2025, a 50% increase compared to 200 patients added during the fourth quarter of 2024.2,800 patients being treated with LUMRYZ as of March 31, 2025 compared to 2,500 at December 31, 2024.Provides guidance for the quarter ending June 30, 2025 of $60 - $63 million in net product revenue and cash operating expenses of $45 - $50 million.Raises 2025 full year guidance to $255 - $265 million in net product revenue, cash operating expenses of $180 - $200 million, and cash flow of $30 - $40 million. Corporate and Pipeline Updates: Corporate On May 6, 2025, the United States Court of Appeals for the Federal Circuit (“Federal Circuit”) ruled in Avadel’s favor, overturning important parts of the injunction imposed by the U.S. District Court for the District of Delaware regarding LUMRYZ’s potential use as a treatment for indications beyond narcolepsy. With this ruling, Avadel can pursue and be granted U.S Food and Drug Administration (FDA) approval for LUMRYZ’s use in IH. Initiated four patent infringement lawsuits against Jazz Pharmaceuticals since the beginning of 2025, alleging certain uses of Jazz’s Xywav product, according to its corresponding labeling, infringe claims of five different Avadel patents. LUMRYZ for IH Patient enrollment of REVITALYZ, a Phase 3 double-blind, placebo-controlled, randomized withdrawal, multicenter study designed to evaluate the efficacy and safety of LUMRYZ in IH, remains on track to complete by the end of 2025. LUMRYZ for Narcolepsy Completed the implementation of investments to accelerate market adoption of LUMRYZ, including the expansion of Avadel’s field sales and reimbursement, nurse care navigator, and patient ambassador teams.Announced the publication of six manuscripts in a CNS Drugs supplement titled, “A New Dawn in the Management of Narcolepsy,” which cover clinical management, shared decision-making and goal setting for people with narcolepsy and their clinicians. These manuscripts underscore the impact of nighttime sleep disturbances on narcolepsy patients and highlight the robust data supporting LUMRYZ in narcolepsy.Together with nference, announced the publication of a paper in the online Journal of Clinical Neuroscience, titled “Characterization and Treatment Patterns of Patients Treated With Immediate-Release Sodium Oxybate for Narcolepsy: A Propensity-Matched Cohort Study.” This details real-world data on comorbidities and compares treatment patterns of people treated for narcolepsy with immediate-release sodium oxybate with untreated patients. Overview of First Quarter Financial Results Avadel recognized $52.5 million in net product revenue from sales of LUMRYZ for the quarter ended March 31, 2025, a 93% increase compared to $27.2 million for the same period in 2024. Total operating expenses in the quarter ended March 31, 2025 were $49.9 million, a 3% decrease compared to $51.7 million for the same period in 2024. R&D expenses for the quarter ended March 31, 2025 were $4.3 million compared to $3.1 million for the same period in 2024. The increase was driven primarily by costs associated with REVITALYZ. SG&A expenses for the quarter ended March 31, 2025 were $45.6 million compared to $48.6 million for the same period in 2024. The decrease was driven primarily by lower legal costs in the period, offset by an increase in LUMRYZ commercial costs, including increased headcount and selling and marketing expenses. Net loss for the quarter ended March 31, 2025 was to $4.9 million, or ($0.05) per diluted share compared to net loss of $27.3 million, or ($0.30) per diluted share, for the same period in 2024. Cash, cash equivalents and marketable securities were $66.5 million at March 31, 2025 compared to $73.8 million at December 31, 2024. As recently disclosed, Avadel operates a diversified supply chain, with the active pharmaceutical ingredient (API) in LUMRYZ manufactured by two contract development and manufacturing organizations (CDMOs) located in the U.S. The finished LUMRYZ commercial product is approved to be manufactured by one CDMO in the U.S. and another in Europe, and all primary packaging of LUMRYZ is conducted in the U.S. If needed, Avadel has the capacity to manufacture LUMRYZ entirely in the U.S. Conference Call Details: A live audio webcast of the call can be accessed by visiting the investor relations section of the Company’s website, www.avadel.com. A replay of the webcast will be archived on Avadel’s website for 90 days following the event. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. About LUMRYZ™ (sodium oxybate) for extended-release oral suspension LUMRYZ is an extended-release sodium oxybate medication approved by the FDA on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. On October 16, 2024, LUMRYZ was additionally approved as a once-at-bedtime treatment for cataplexy or EDS in pediatric patients seven years of age and older with narcolepsy. The FDA approval of LUMRYZ was supported by results from REST-ON™, a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial in adults with narcolepsy. LUMRYZ demonstrated statistically significant and clinically meaningful improvements in the three co-primary endpoints: EDS (MWT), clinicians’ overall assessment of patients’ functioning (CGI-I), and cataplexy attacks, for all three evaluated doses when compared to placebo. With its approvals in May 2023 and October 2024, the FDA also granted seven years of Orphan Drug Exclusivity to LUMRYZ for the treatment of cataplexy or EDS in adults with narcolepsy and in pediatric patients seven years of age and older with narcolepsy (respectively) due to a finding of clinical superiority of LUMRYZ relative to currently available oxybate treatments. In particular, the FDA found that LUMRYZ makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose. About Avadel Pharmaceuticals plc Avadel Pharmaceuticals plc (Nasdaq: AVDL) is a biopharmaceutical company focused on transforming medicines to transform lives. Our approach includes applying innovative solutions to the development of medications that address the challenges patients face with current treatment options. Avadel’s commercial product, LUMRYZ, was approved by the U.S. Food & Drug Administration (FDA) as the first and only once-at-bedtime oxybate for the treatment of cataplexy or EDS in patients seven years of age and older with narcolepsy. For more information, please visit www.avadel.com Avadel intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcast. IMPORTANT SAFETY INFORMATION WARNING: Taking LUMRYZ™ (sodium oxybate) with other central nervous system (CNS) depressants, such as medicines used to make you 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 LUMRYZ (sodium oxybate) is a form of gamma hydroxybutyrate (GHB), a controlled substance. Abuse or misuse of illegal GHB alone or with other CNS depressants (drugs that cause changes in alertness or consciousness) have 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 have any of these serious side effects.Because of these risks, LUMRYZ is available only by prescription and filled through certified pharmacies in the LUMRYZ REMS. You must be enrolled in the LUMRYZ REMS to receive LUMRYZ. Further information is available at www.LUMRYZREMS.com or by calling 1-877-453-1029. INDICATIONSLUMRYZ (sodium oxybate) for extended-release oral suspension is a prescription medicine used to treat the following symptoms in patients seven years and older with narcolepsy: sudden onset of weak or paralyzed muscles (cataplexy)excessive daytime sleepiness (EDS) Do not take LUMRYZ 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 LUMRYZ in a safe place to prevent abuse and misuse. Selling or giving away LUMRYZ may harm others and is against the law. Tell your doctor if you or your child have ever abused or been dependent on alcohol, prescription medicines or street drugs. Anyone who takes LUMRYZ 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 six (6) hours after taking LUMRYZ. Those activities should not be done until you know how LUMRYZ affects you. Falling asleep quickly, including while standing or while getting up from the bed, has led to falls with injuries that have required some people to be hospitalized. LUMRYZ can cause serious side effects, including the following: Breathing problems, including slower breathing, trouble breathing and/or short periods of not breathing while sleeping (e.g., sleep apnea). People who already have breathing or lung problems have a higher chance of having breathing problems when they take LUMRYZ.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 and difficulty concentrating. 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 or your child have symptoms of mental health problems or a change in weight or appetite.Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you or your child start sleepwalking. Tell your doctor if you or your child are on a salt-restricted diet or have high blood pressure, heart failure or kidney problems. LUMRYZ contains a lot of sodium (salt) and may not be right for you.The most common side effects of LUMRYZ in adults include nausea, dizziness, bedwetting, headache and vomiting. Your side effects may increase when you take higher doses of LUMRYZ. The most common side effects in children include nausea, bedwetting, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking. LUMRYZ 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 LUMRYZ. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see full Prescribing Information, including BOXED Warning. Cautionary Disclosure Regarding Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements relate to our future expectations, beliefs, plans, strategies, objectives, results, conditions, financial performance, prospects or other events. Such forward-looking statements include, but are not limited to, expectations regarding the potential therapeutic benefit of LUMRYZ; the success of the commercialization of LUMRYZ; the anticipated market demand and sales opportunity of LUMRYZ, including assumptions regarding the number of patients using LUMRYZ; the Company’s idiopathic hypersomnia clinical study for LUMRYZ, including enrollment and timing related thereto; the litigation involving Jazz Pharmaceuticals Inc., including the potential benefits of the Federal Circuit decision; the Company’s ability to offer open-label extensions and initiate new clinical trials for LUMRYZ in indications beyond narcolepsy; the Company’s ability to seek and obtain FDA approval for, as well as, commercially launch LUMRYZ for indications beyond narcolepsy; the Company’s expectations regarding the strength and diversity of its supply chain; the Company’s financial guidance for the 2025 fiscal year, including the expected number of patients and net revenue; anticipated outcomes of any legal proceedings and lawsuits; and the Company’s anticipated financial condition, expenses, uses of capital and other future financial results. In some cases, forward-looking statements can be identified by use of words such as “will,” “may,” “could,” “believe,” “expect,” “look forward,” “on track,” “guidance,” “anticipate,” “estimate,” “project,” “next steps” and similar expressions and the negatives thereof (if applicable). The Company’s forward-looking statements are based on estimates and assumptions that are made within the bounds of our knowledge of our business and operations and that we consider reasonable. However, the Company’s business and operations are subject to significant risks, and, as a result, there can be no assurance that actual results and the results of the company’s business and operations will not differ materially from the results contemplated in such forward-looking statements. Factors that could cause actual results to differ from expectations in the Company’s forward-looking statements include the risks and uncertainties described in the “Risk Factors” section of Part I, Item 1A of the Company’s most recent Annual Report on Form 10-K and subsequent filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made and are not guarantees of future performance. Accordingly, you should not place undue reliance on forward-looking statements. The Company does not undertake any obligation to publicly update or revise our forward-looking statements, except as required by law. Investor Contact:Austin MurtaghPrecision AQAustin.Murtagh@precisionAQ.com (212) 698-8696 Media Contact:Lesley StanleyReal Chemistrylestanley@realchemistry.com(609) 273-3162 AVADEL PHARMACEUTICALS PLCCONDENSED CONSOLIDATED STATEMENTS OF LOSS(In thousands, except per share data)(Unaudited) Three Months Ended March 31, 2025 2024 Net product revenue $52,511 $27,178 Cost of products sold 5,577 1,522 Gross profit 46,934 25,656 Operating expenses: Research and development expenses 4,354 3,068 Selling, general and administrative expenses 45,581 48,623 Total operating expense 49,935 51,691 Operating loss (3,001) (26,035)Investment and other income, net 397 1,378 Interest expense (2,238) (2,592)Loss before income taxes (4,842) (27,249)Income tax provision 78 93 Net loss $(4,920) $(27,342) Net loss per share - basic $(0.05) $(0.30)Net loss per share - diluted $(0.05) $(0.30) Weighted average number of shares outstanding - basic 96,601 91,693 Weighted average number of shares outstanding - diluted 96,601 91,693 AVADEL PHARMACEUTICALS PLCCONDENSED CONSOLIDATED BALANCE SHEETS(In thousands, except per share data) March 31, 2025 December 31, 2024 (Unaudited) ASSETS Current assets: Cash and cash equivalents $56,370 $51,371 Marketable securities 10,114 22,406 Accounts receivable, net 41,581 34,097 Inventories 20,406 20,298 Prepaid expenses and other current assets 10,787 6,036 Total current assets 139,258 134,208 Property and equipment, net 307 453 Operating lease right-of-use assets 2,896 1,702 Goodwill 16,836 16,836 Other non-current assets 8,652 11,037 Total assets $167,949 $164,236 LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Current portion of operating lease liability $706 $582 Accounts payable 9,116 7,328 Accrued expenses 40,917 40,651 Other current liabilities 194 273 Total current liabilities 50,933 48,834 Long-term operating lease liability 2,189 1,122 Royalty financing obligation 35,518 35,249 Other non-current liabilities 5,239 5,183 Total liabilities 93,879 90,388 Shareholders’ equity: Preferred shares, nominal value of $0.01 per share; 50,000 shares authorized; zero issued and outstanding at March 31, 2025 and December 31, 2024 — — Ordinary shares, nominal value of $0.01 per share; 500,000 shares authorized; 96,632 issued and outstanding at March 31, 2025 and 96,518 issued and outstanding at December 31, 2024 966 965 Additional paid-in capital 896,663 891,791 Accumulated deficit (799,247) (794,328)Accumulated other comprehensive loss (24,312) (24,580)Total shareholders’ equity 74,070 73,848 Total liabilities and shareholders’ equity $167,949 $164,236 AVADEL PHARMACEUTICALS PLCCONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(In thousands)(Unaudited) Three Months Ended March 31, 2025 2024 Cash flows from operating activities: Net loss $(4,920) $(27,342)Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 825 541 Share-based compensation expense 4,183 5,389 Other adjustments 70 (719)Net changes in assets and liabilities Accounts receivable (7,484) (10,589)Inventories (66) (1,260)Prepaid expenses and other current assets (3,016) (6,082)Accounts payable & other current liabilities 1,779 7,528 Accrued expenses 218 3,415 Other assets and liabilities 179 (585)Net cash used in operating activities (8,232) (29,704) Cash flows from investing activities: Proceeds from sales of marketable securities 17,808 119,066 Purchases of marketable securities (5,491) (97,679)Net cash provided by investing activities 12,317 21,387 Cash flows from financing activities: Proceeds from issuance of shares off the at-the-market offering program — 9,250 Proceeds from stock option exercises and employee share purchase plan 690 3,940 Net cash provided by financing activities 690 13,190 Effect of foreign currency exchange rate changes on cash and cash equivalents 224 (246) Net change in cash and cash equivalents 4,999 4,627 Cash and cash equivalents at January 1, 51,371 31,167 Cash and cash equivalents at March 31, $56,370 $35,794

– Total revenues of $898 million in 1Q25 – – Xywav ® and Epidiolex ® revenues grew 9% and 10% year-over-year, respectively, in 1Q25 – – Completed submission of sNDA for Zepzelca ® in 1L ES-SCLC – – Affirming 2025 revenue guidance; updating financial guidance to reflect Chimerix acquisition and impact of certain Xyrem® antitrust litigation settlements – DUBLIN, May 6, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced financial results for the first quarter of 2025 and updated financial guidance for 2025. "In the first quarter of 2025, our focus on commercial execution resulted in total revenues of $898 million, led by the strong performance of Xywav and Epidiolex. In addition, our team continues to receive positive feedback from healthcare providers on the launch of Ziihera® in its first approved indication of 2L HER2+ BTC. We are affirming our 2025 total revenue guidance range of $4.15 - $4.40 billion, reflecting our confidence in our commercial portfolio delivering top-line growth this year," said Bruce Cozadd, chairman and chief executive officer, Jazz Pharmaceuticals. "We continue to make meaningful progress across our pipeline. We are pleased to report that we have submitted a supplemental New Drug Application for Zepzelca for maintenance therapy in first-line extensive-stage small cell lung cancer. In addition, we recently completed the acquisition of Chimerix, adding a near-term commercial opportunity to our late-stage pipeline that addresses a significant unmet need for patients with H3 K27M-mutant diffuse glioma, a rare, high-grade brain tumor that most commonly affects children and young adults. We also advanced multiple trials across our zanidatamab development program and expect top-line data readout from the HERIZON-GEA-01 trial in 1L GEA in the second half of 2025." Key Highlights Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 2H25. Submitted sNDA for Zepzelca in combination with atezolizumab (Tecentriq®) as maintenance therapy in 1L ES-SCLC based on the potentially practice-changing results from the Phase 3 IMforte trial. Data from trial to be presented at the 2025 ASCO Annual Meeting in June 2025. Acquisition of Chimerix added dordaviprone to late-stage pipeline, representing near-term commercial opportunity; PDUFA target data of August 18, 2025. Top-line growth expected in 2025; affirmed 2025 total revenue guidance of $4.15 - $4.40 billion, representing 5% growth at the midpoint. Total revenue guidance is underpinned by expected continued growth of Jazz's diversified commercial portfolio. Business Updates Commercial Updates Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution: Xywav net product sales increased 9% to $344.8 million in 1Q25 compared to 1Q24. Meaningful Xywav net patient adds in 1Q25 (approximately 450 patients) with approximately 14,600 active Xywav patients exiting 1Q25, comprised of: Approximately 10,375 narcolepsy patients. Approximately 4,225 idiopathic hypersomnia (IH) patients, with 325 net patient adds. Two presentations at the American Academy of Neurology Annual Meeting provided updated results from the open-label, single-arm, Phase 4 DUET trial of adults with narcolepsy or IH. The results demonstrated statistically significant improvements from baseline to end of treatment in Epworth Sleepiness Scale (ESS) scores, reduced sleep stage shifts, increased deep sleep and reduced number of awakenings among adults with narcolepsy treated with Xywav. In adults with IH, Xywav treatment showed improvements in ESS and IH Severity Scale scores. Xywav is the only low-sodium oxybate, the #1 branded treatment for narcolepsy1 and the only U.S. Food and Drug Administration (FDA)-approved therapy to treat IH. Xyrem (sodium oxybate) oral solution and high-sodium oxybate authorized generic (AG) royalties: Xyrem net product sales decreased 42% to $37.2 million in 1Q25 compared to 1Q24. Royalties from high-sodium oxybate AGs were $48.9 million in 1Q25. Epidiolex/ Epidyolex® (cannabidiol): Epidiolex/Epidyolex net product sales increased 10% to $217.7 million in 1Q25 compared to 1Q24. Outside of the U.S., Epidyolex is approved in more than 35 countries. Remain confident in achieving blockbuster status for Epidiolex/Epidyolex in 2025. Rylaze®/ Enrylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales decreased 8% to $94.2 million in 1Q25 compared to 1Q24. This decrease was driven by headwinds from an update to Children's Oncology Group (COG) pediatric treatment protocols for acute lymphoblastic leukemia made in mid-2024 that impacted timing of asparaginase administration. The impact to Rylaze net product sales due to COG protocol updates is expected to normalize during 2Q25. Zepzelca (lurbinectedin): Zepzelca net product sales decreased 16% to $63.0 million in 1Q25 compared to 1Q24. This decrease was driven by increased competition in second-line (2L) small cell lung cancer (SCLC) and treatment protocol updates delaying progression in first-line (1L) limited-stage SCLC patients to the 2L setting. The Company submitted a supplemental New Drug Application (sNDA) for Zepzelca's use in combination with atezolizumab as maintenance therapy in 1L extensive-stage (ES) SCLC for patients who have not progressed after induction chemotherapy. Potentially practice-changing data from the Phase 3 IMforte trial, which showed a statistically significant and clinically meaningful benefit in both progression-free survival (PFS) and overall survival for the Zepzelca and atezolizumab combination for ES-SCLC patients receiving this treatment in the first-line maintenance setting, was accepted for an oral presentation at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting. This is the first presentation of data from the IMforte trial. Ziihera (zanidatamab-hrii): Ziihera net product sales were $2.0 million in 1Q25 following product launch in December 2024. On April 25, 2025, the Company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending the conditional marketing authorization of zanidatamab in 2L BTC (biliary tract cancer). The CHMP recommendation is being reviewed by the European Commission. Corporate Development Chimerix Acquisition: The Company completed its acquisition of Chimerix in April 2025, adding dordaviprone to its late-stage pipeline. Dordaviprone is a novel first-in-class small molecule treatment in development for H3 K27M-mutant diffuse glioma, a rare, high-grade brain tumor that most commonly affects children and young adults. Key Pipeline Highlights Zanidatamab: The pivotal HERIZON-GEA-01 trial, evaluating zanidatamab in 1L gastroesophageal adenocarcinoma (GEA), is expected to read out in 2H25 based on the most recent assessment of progression events. Recruitment for the trial has been completed. New data from an ongoing Phase 2 trial of zanidatamab in combination with chemotherapy for the first-line treatment of HER2-positive metastatic GEA, including more mature overall survival data, was accepted for a rapid oral presentation at the 2025 ASCO Annual Meeting. The Phase 3 EmpowHER-BC-303 trial 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 continues to enroll patients. The Phase 2 pan-tumor trial to evaluate HER2-positive solid tumors continues to enroll patients. Dordaviprone: A New Drug Application for accelerated approval of dordaviprone in recurrent H3 K27M-mutant diffuse glioma was accepted and granted Priority Review by FDA. FDA has set a target Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. The ongoing Phase 3 ACTION trial is evaluating dordaviprone in newly diagnosed, non-recurrent H3 K27M-mutant diffuse glioma patients following radiation treatment, potentially extending its use into the first-line setting. Data on the efficacy and safety of dordaviprone from prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients was accepted for an oral presentation at the 2025 ASCO Annual Meeting. Financial Highlights GAAP net loss for 1Q25 was $(92.5) million, or $(1.52) per diluted share, compared to $(14.6) million, or $(0.23) per diluted share, for 1Q24. Non-GAAP adjusted net income for 1Q25 was $105.2 million, or $1.68 per diluted share, compared to $178.4 million, or $2.63 per diluted share, for 1Q24. The GAAP net loss and non-GAAP adjusted net income for 1Q25 included an expense of $172.0 million related to certain Xyrem antitrust litigation settlements, which impacted our GAAP and non-GAAP results by $146.3 million (net of tax of $25.7 million) or $2.38 per share on a GAAP basis and $2.34 per share on a non-GAAP adjusted basis. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release. Total Revenues Total revenues for 1Q25 were in line with 1Q24. Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, was $654.1 million in 1Q25, an increase of 4% compared to $630.9 million in 1Q24. The increase in 1Q25 was due to higher Xywav and Epidiolex/Epidyolex net product sales, partially offset by decreased Xyrem net product sales. Oncology net product sales were $229.4 million in 1Q25, a decrease of 11% compared to $257.5 million in 1Q24. The decrease in 1Q25 was primarily due to lower net product sales of Zepzelca, Rylaze/Enrylaze and Defitelio/defibrotide. In 1Q25, Rylaze net product sales were negatively impacted due to an update to the COG pediatric treatment protocols for ALL, which impacts the timing of asparaginase administration. Operating Expenses and Effective Tax Rate Changes in operating expenses in 1Q25 over the prior year period are primarily due to the following: Cost of product sales, on a GAAP and non-GAAP adjusted basis, increased in 1Q25 compared to the same period in 2024, primarily due to changes in product mix and higher inventory provisions. SG&A expenses, on a GAAP and non-GAAP adjusted basis, increased in 1Q25 compared to the same period in 2024, primarily due to certain Xyrem antitrust litigation settlements of $172.0 million incurred in 1Q25. Research and development (R&D) expenses, on a GAAP and non-GAAP adjusted basis, decreased in 1Q25 primarily due to lower clinical study costs primarily related to zanidatamab, as a result of timing of clinical trial activities, and JZP385 (essential tremor) and JZP150 (post-traumatic stress disorder) following discontinuation of these programs. Acquired in-process research and development (IPR&D) in 1Q24, on a GAAP and non-GAAP adjusted basis, related to an upfront payment made in connection with our asset purchase agreement with Redx Pharma plc. Cash Flow and Balance Sheet As of March 31, 2025, cash, cash equivalents and investments were $2.6 billion, and the outstanding principal balance of the Company's long-term debt was $5.4 billion. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $885.0 million. For the three months ended March 31, 2025, the Company generated $429.8 million of cash from operations reflecting strong business performance and continued financial discipline. In January 2025, the Company made a voluntary prepayment of $750.0 million principal amount on the Term Loan B. In April 2025, the Company acquired Chimerix for a total consideration of approximately $935 million, which was funded with cash and cash equivalents. 2025 Financial Guidance 1 Jazz Pharmaceuticals is updating its full year 2025 financial guidance primarily to reflect the impact of the Chimerix acquisition and certain Xyrem antitrust litigation settlements. 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 2025 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: 5080203 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 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. In this regard, commencing with the first quarter of 2025, the Company is no longer including an adjustment for non-cash interest expense in the Company's non-GAAP adjusted financial measures. For purposes of comparability, non-GAAP adjusted financial measures for the first quarter of 2024 have been updated to reflect this change. 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 2025 financial guidance and the Company's expectations related thereto, including with respect to anticipated catalysts; expectations that Epidiolex will achieve blockbuster status in 2025; the ability to generate growth and long-term shareholder value; anticipated benefits and expenses relating to the Company's acquisition of Chimerix; the Company's advancement of pipeline programs and the timing of development activities, regulatory activities and submissions related thereto; the potential for a near-term commercial launch of dordaviprone in the U.S. if approved; the potential of the ongoing Phase 3 ACTION trial to confirm clinical benefit of dordaviprone in recurrent H3 K27M-mutant diffuse glioma and extend to use in first-line patients; planned or anticipated clinical trial events, including with respect to initiations, enrollment and data read-outs, and the anticipated timing thereof, including: top-line PFS data from a Phase 3 trial of zanidatamab in 1L GEA; and the Company's development, regulatory and commercialization strategy; 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, including Zepzelca's potential to change current practice in 1L ES-SCLC; 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 international tariffs and trade restrictions and 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; the ability of the parties to obtain court approval of certain Xyrem class action settlement agreements and the risk that the Company may incur other charges or cash expenditures not currently contemplated due to unanticipated events that may occur, including in connection with certain Xyrem class action settlement agreements, and the risk that the Company is unable to reach settlement agreements with other Xyrem antitrust plaintiffs that are not party to certain Xyrem class action settlement agreements; 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, including Chimerix and the acquired product candidate dordaviprone; 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, 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, 2024, and future filings and reports by the Company, including the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2025. 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. The Company's 2025 financial guidance includes the anticipated results of the acquired Chimerix operations from the date of acquisition April 21, 2025 and an acquired IPR&D expense as a result of the Company's expected accounting treatment of Chimerix as an asset acquisition. This guidance remains subject to final acquisition accounting. Contacts: Investors: Jeff Macdonald Executive Director, 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 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED