Sodium Oxybate

Avadel Pharmaceuticals can try to expand the use of its blockbuster narcolepsy drug after a federal appeals court overturned an order that had barred it from filing for FDA approval for use in idiopathic hypersomnia. The US Court of Appeals for the Federal Circuit’s ruling is a win for Avadel’s Lumryz and is the latest development in a longstanding patent dispute with rival Jazz Pharmaceuticals. The company said it’s now “on track to complete enrollment” in a Phase 3 study of Lumryz in idiopathic hypersomnia by the end of the year. The case centered on whether applying for a new indication of Lumryz would infringe claims in Jazz’s patent, and if so, what the proper remedy is. A lower court in August prohibited Avadel from seeking approval and marketing Lumryz for the treatment of idiopathic hypersomnia. The appeals court on Tuesday declined to determine whether such an application would qualify as an act of infringement. But, it said that if it does, the lower court order is unlawful because it exceeds the scope of remedies available to patent owners under the Hatch Waxman Act. And if it doesn’t, it’s “too speculative and tenuous to reasonably conclude” that an injunction is needed to prevent future infringement, the appeals court said. The court revoked the injunction and sent the case back to the lower court. It also reversed an order that blocked Avadel from starting new clinical trials for Lumryz. The decision “gives us a pathway to file and secure and seek FDA approval. And that is a very important next step in our strategy here to be able to pursue that,” Avadel CEO Greg Divis said Wednesday on the company’s first-quarter earnings call, according to an AlphaSense transcript. “I’ll remind everybody, 24 hours ago, we were enjoined from doing that. And now we’re not, which is really, really important from that perspective for us as we think about our strategy to advance Lumryz in [idiopathic hypersomnia] or even other potential indications as we do that work,” Divis said. Lumryz launched in 2023 and is approved by the FDA for the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy. It brought in $52.5 million in revenue in the first quarter of the year, a 93% increase from a year prior, according to a Wednesday earnings release. A spokesperson for Jazz, whose key narcolepsy drugs include Xyrem and Xywav, said in a statement to Endpoints News that it is “evaluating potential next steps” in the case. “The issue of whether Avadel is permitted to seek FDA approval of Lumryz for [idiopathic hypersomnia] has been sent back to the District Court for reconsideration in further proceedings,” the spokesperson added. “The Federal Circuit’s opinion does not change the fact that Avadel admitted to infringing Jazz’s intellectual property, and that a jury found that IP to be valid.” Editor’s Note: This story was updated with comment from Jazz.

-- 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