Dextroamphetamine sulfate

– Post-hoc analysis from pivotal Phase 3 REST-ON trial confirmed the efficacy of LUMRYZ in study participants who were and were not using a stable dose of an alerting agent – – Baseline data underscore that alerting agents alone are often insufficient for excessive daytime sleepiness – DUBLIN, Sept. 25, 2024 (GLOBE NEWSWIRE) -- Avadel Pharmaceuticals plc (Nasdaq: AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, today announced the publication of results of a post-hoc analysis from the completed pivotal Phase 3 REST-ON clinical trial. Results demonstrated clinically significant improvements from baseline in wakefulness, overall condition, number of weekly cataplexy episodes, and excessive daytime sleepiness in patients taking LUMRYZ (sodium oxybate) compared to those taking placebo, regardless of concomitant use of alerting agents. The paper, titled “Efficacy of Once-Nightly Sodium Oxybate (FT218) on Daytime Symptoms in Individuals With Narcolepsy With or Without Concomitant Alerting Agent Use: A Post Hoc Analysis From the Phase 3 REST-ON Trial,” was published online in Sleep Medicine. “Treatment of narcolepsy often requires multiple medicines to adequately control symptoms. Alerting agents, including stimulants and wake-promoting agents, are often the first treatment prescribed for narcolepsy,” said Richard K. Bogan, MD, FCCP, FAASM, Associate Clinical Professor at the University of South Carolina School of Medicine and Medical University of South Carolina in Charleston. “In REST-ON, subjects in the alerting agent subgroup were also pathologically sleepy at baseline and could only remain awake for approximately five minutes during the maintenance of wakefulness test. Both subgroups had marked improvement on daytime sleepiness with once-at-bedtime LUMRYZ. While this would be expected clinically, this type of post-hoc analysis has not been previously undertaken to evaluate the addition of an oxybate to a stable alerting agent regimen.” The randomized, double-blind, placebo-controlled, pivotal Phase 3 REST-ON trial evaluated once-at-bedtime LUMRYZ in adults with narcolepsy. Primary endpoints included change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy episodes. Secondary endpoint was change from baseline in the Epworth Sleepiness Scale (ESS) score (a measure of sleepiness in everyday situations). Dauvilliers et al. evaluated the efficacy of LUMRYZ on these endpoints in participants with narcolepsy who were taking and not taking alerting agents (modafinil, armodafinil, various amphetamines, dexamphetamine sulfate and methylphenidate hydrochloride). A total of 119 study participants (63%) were taking alerting agents and 71 (37%) were not. Results of the post-hoc analysis: Significant improvements with LUMRYZ at all doses were seen versus placebo for MWT, CGI-I and number of weekly cataplexy episodes (p<0.05) regardless of alerting agent use, which were also clinically meaningful.Similarly, ESS was significantly improved with LUMRYZ at all doses versus placebo in the group taking alerting agents (p<0.05), with significant improvements for the non-alerting agent group at the 7.5 g and 9 g dose, and directional improvement at Week 3 with the 6 g dose. “It is important for clinicians and people with narcolepsy to recognize that alerting agents alone may not be sufficient to treat excessive daytime sleepiness. As with other oxybates trials, a high proportion of subjects were on stable doses of alerting agents, yet still qualified for study entry based upon pathological sleepiness,” said Jennifer Gudeman, Pharm.D., Senior Vice President, Medical and Clinical Affairs at Avadel. “These data should help initiate discussions between patients and clinicians to assess whether an alerting agent regimen alone is sufficiently managing their narcolepsy. Additionally, for the 37% of participants not on alerting agents, these results show that LUMRYZ monotherapy may be sufficient to manage narcolepsy symptoms.” About LUMRYZ™ (sodium oxybate) for extended-release oral suspensionLUMRYZ 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. 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, clinicians’ overall assessment of patients’ functioning (CGI-I), and cataplexy attacks, for all three evaluated doses when compared to placebo. With its approval, the FDA also granted seven years of Orphan Drug Exclusivity to LUMRYZ for the treatment of cataplexy or EDS in adults with narcolepsy 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. 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. INDICATIONS LUMRYZ (sodium oxybate) for extended-release oral suspension is a prescription medicine used to treat the following symptoms in adults with narcolepsy: sudden onset of weak or paralyzed muscles (cataplexy)excessive daytime sleepiness (EDS) It is not known if LUMRYZ is safe and effective in people less than 18 years of age.Do not take LUMRYZ if you take 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 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 have or had depression or have tried to harm yourself. Call your doctor right away if you have symptoms of mental health problems or a change in weight or appetite.Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you start sleepwalking. Tell your doctor if you are on a salt-restricted diet or if you 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. 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 www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see full Prescribing Information, including BOXED Warning. About Avadel Pharmaceuticals plcAvadel 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 excessive daytime sleepiness (EDS) in adults with narcolepsy. For more information, please visit www.avadel.com. Cautionary Disclosure Regarding Forward-Looking StatementsThis 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 in treating EDS, including its efficacy in improving narcolepsy symptoms regardless of concomitant use of an alerting agent; alerting agents alone not being sufficient for treatment of EDS; and LUMRYZ monotherapy being sufficient to manage narcolepsy symptoms. In some cases, forward-looking statements can be identified by the 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 Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on February 29, 2024, and subsequent SEC filings. 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. AvadelInvestor Contact:Courtney MogerleyPrecision AQCourtney.Mogerley@precisionAQ.com(212) 698-8687 Media Contact:Lesley StanleyReal Chemistrylestanley@realchemistry.com (609) 273-3162

这项研究表明，ADHD药物治疗与卒中、心力衰竭和复合结局的10年标准化风险升高有关，并且，每日服用＞1 DDD的患者10年标准化风险可能具有剂量反应关系。 丹麦哥本哈根大学医院的研究团队利用丹麦国家健康登记处的数据，开展了一项观察性研究，分析了ADHD药物与急性冠脉综合征、卒中和心力衰竭的长期风险的关联。他们发现，与既往服药者相比，当前每日接受≥1规定每日剂量ADHD药物者的卒中、心力衰竭和复合心血管结局风险分别增加20%、70%和30%。 研究结果发表在《美国心脏病学会杂志》上[1]。 研究使用了丹麦国家健康登记处的数据，具有良好的代表性。研究纳入了1998-2020年间所有接受首次接受ADHD药物治疗的成年人，使用的药物包括哌甲酯、托莫西汀、利右苯丙胺、右苯丙胺和莫达非尼，并且排除了患多发性硬化症、发作性睡病患者和超适应证的姑息治疗（因癌症接受阿片类药物治疗）患者。 研究人员共确认了73264名成年ADHD患者，基线时，26357人（36%）停止治疗，被划分为既往服药组，平均年龄30岁，其余正在接受治疗的患者按照服药剂量分为低剂量组（＜1规定每日剂量[DDD]）和高剂量组（≥1 DDD），分别有31211人（43%）和15696人（21%），平均年龄分别为31岁和33岁。他们还创建了一个包含145456名未患ADHD和未接受ADHD药物治疗的匹配对照组。 参与者最长接受10年的随访，中位为6.5年。随访期间，低剂量组和高剂量组分别发生了187例和159例急性冠脉综合征，345例和159例卒中，167例和87例心力衰竭，相应的，匹配对照组和既往服药组的三种心血管疾病的发生数量分别为646例和169例，1031例和326例，579例和140例。 研究人员据此计算了10年内，每一组参与者每年每种疾病的标准化绝对风险。 10年内的匹配对照（蓝）、既往使用（橙）、低剂量（黑）和高剂量组（紫）的急性冠脉综合征、卒中、心力衰竭和复合结局在10年内每年的标准化疾病风险 基于10年标准化绝对风险，研究人员以既往服药组为对照计算了其他组的相对风险，他们发现，高剂量组与卒中风险增加20%、心力衰竭风险增加70%和包含急性冠脉综合征、卒中和心力衰竭的复合结局风险增加30%有关，但与急性冠脉综合征风险无关。 匹配对照（蓝）、既往使用（橙）、低剂量（黑）和高剂量组（紫）的急性冠脉综合征、卒中、心力衰竭和复合结局的10年标准化绝对风险和相对风险 与匹配对照组相比，低剂量组和高剂量组均与心血管疾病的10年标准化绝对风险增加有关，复合结局风险分别增加40%和70%。 补充分析显示，根据性别、年龄和伴随治疗分组的亚组分析显示出了相似的风险关联。40岁以上和伴随精神疾病药物或非甾体抗炎药物治疗的参与者有最高的卒中、心力衰竭和复合结局10年标准化风险。 综上，这项研究表明，ADHD药物治疗与卒中、心力衰竭和复合结局的10年标准化风险升高有关，并且，每日服用＞1 DDD的患者10年标准化风险可能具有剂量反应关系。 在同期发表的评论文章中[2]，评论人员肯定了研究的价值，同时也指出，研究的几点局限性需要注意，例如，ADHD本身也与心血管疾病风险增加有关，因此与其他非随机的流行病学研究一样，存在疾病本身的混淆风险，高剂量的治疗可能意味着更严重的ADHD或其他与心血管风险增加独立相关的疾病。 另外，参与者中有较高比例同时服用其他精神疾病药物，如18.6%同时服用抗精神疾病药物，34.9%同时服药抗抑郁药物，这些患者的主要疾病是否有可能是抑郁症、焦虑症或其他精神疾病，而非ADHD？同样，非甾体抗炎药物也与心血管疾病风险增加有关，同时服用的参与者在高剂量组更为普遍。 研究人员指出，在年轻的ADHD患者中，长期服用ADHD药物与心血管疾病的潜在联系应该受到精神科医生的重视，他们希望这项研究和其他观察性研究的发现能够启发未来的临床研究。 参考文献： [1] Holt A, Strange J E, Rasmussen P V, et al. Long-term cardiovascular risk associated with treatment of attention-deficit/hyperactivity disorder in adults[J]. Journal of the American College of Cardiology, 2024, 83(19): 1870-1882. [2] Alexander G C, Moore T J, Brass E P. Long-Term Cardiovascular Risks of Psychostimulant Drugs for Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD)[J]. Journal of the American College of Cardiology, 2024, 83(19): 1883-1885.