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

来源：药渡 撰文：天际微步    编辑：哦呼 武田制药（武田药品工业株式会社，Takeda）是一家位于日本东京的老牌药企，从中草药销售起步已经拥有243年历史，如今已成为亚洲最大的制药公司，在全球MNC药企中排名TOP20之列。2023财年武田制药的营收为4.26万亿日元，同比增长5.9%，在全球药企中的排名为第13位。 与强生、辉瑞等其他大MNC有较强自研能力不同，武田制药从药物销售贸易起步，积攒了原始资本，后在仿制美国药上布局，凭借四大me too品种（亮丙瑞林微球、兰索拉唑、坎地沙坦、吡格列酮）崛起。在这过程中虽有布局自主研发管线，但效果不佳，只得不断地并购或者交易来拓展管线，因此武田制药的交易事件相当频繁。 从2005年第一次海外收购美国syrrx inc，武田逐渐形成了以肿瘤、消化、罕见病和神经为主，疫苗和血制品为辅的业务版图。从近两年武田的药物交易事件来看一下武田的重点方向和布局策略变化。 2023年以来武田的药物交易事件盘点 从2023年初开始武田制药就一直在进行内部调整，以应对重磅产品专利到期（替度鲁肽、利右苯丙胺等）带来的业绩冲击。一方面，砍掉尚未见效的早期管线、收缩战线，据公开资料，2023年武田制药共有包括肺癌产品Exkivity、阿尔茨海默病药物DNL-919等18款药物从管线中剔除，还终止了与JCR制药公司的AAV基因治疗，与Noile-Immune的新一代实体瘤CAR-T疗法等的项目合作。在其362个药物管线中，135个已经处于终止状态。 图1.武田制药的管线进展情况（来源：药渡数据） 但另一方面，武田仍继续购进具有上市潜力的管线来形成新增长力。据不完全统计，2023年至2024年6月份，武田制药产生的药物交易有12笔。 表1.2023年以来武田制药的药物交易事件（来源：药渡数据及公开资料整理） 2024年6月14日，武田制药引进亚盛医药的奥雷巴替尼，用于治疗慢性髓性白血病（CML），获得其中国以外的商业化权利。此前，武田已有CML治疗药物泊那替尼，但即将在2026年专利到期，引进奥雷巴替尼可以继续利用此前积累的市场方面优势将新产品大卖，保持在CML治疗领域的领先地位。 2024年5月23日，与上海达歌生物达成独家许可协议，以发现和开发用于肿瘤学、神经科学和炎症领域多个靶点的新型分子胶降解剂。达歌生物将利用其研发平台，针对武田选定的特定疾病靶点，发现、验证和优化分子胶降解剂，在达到一定进展阶段后，这些项目将移交给武田进行进一步开发和商业化。此次主要利用达歌生物的研发创新能力来帮助武田在分子胶降解剂这一类新型药物上进行探索。 2024年5月13日，武田制药引进AC Immune的阿尔茨海默症Aβ疫苗疗法ACI-24.060，阿尔茨海默症也属于武田重点布局的神经性疾病范畴，需要一款重磅新药来塑造竞争力。 2024年4月16日，与Kumquat生物科学达成战略合作和独家全球许可协议，推进新型口服免疫肿瘤药物，武田承担并资助除了由Kumquat主导的1期试验活动之外的所有开发和商业化活动。 2024年1月31日，与Protagonist达成全球许可和合作协议，共同开发罕见血液病药物Rusfertide（其基于多肽的新化学实体），目前正处于关键的 3 期试验，用于治疗真性红细胞增多症。 2023年期间，先后引进和黄医药的用于治疗经治转移性结直肠癌的呋喹替尼， Nimbus Lakshmi的银屑病药物TYK2抑制剂NDI-034858，中国生物制药子公司F-star的肿瘤多特异性抗体免疫疗法，ImmunoGen针对铂耐药卵巢癌的FRα ADC新药ELAHERE，以及AcuraStem的用于治疗肌萎缩性侧索硬化症（ALS）的创新反义寡核苷酸（ASO）疗法AS-202，信念医药治疗B型血友病的AAV基因治疗BBM-H901注射液…… 武田的布局重点和变化？ 从2023年以来的交易情况看，武田的布局焦点，仍然是围绕其四大核心疾病业务领域，包括肿瘤药物（亚盛医药的奥雷巴替尼、Kumquat合作的肿瘤药物、F-star的肿瘤多特异性抗体、ImmunoGen的FRα ADC新药），偏爱和引进了当下热点的ADC和多抗药物；胃肠道药物（和黄的呋喹替尼），通过引进销量不错的呋喹替尼来延续消化疾病领域的优势；罕见病药物（罕见血液病药物Rusfertide、肌萎缩性侧索硬化症的ASO疗法、血友病的AAV基因治疗）。神经疾病药物（AC Immune的阿尔茨海默症Aβ疫苗）、还有自免疾病（银屑病药物TYK2抑制剂）。 从药物类型看，引进新技术、新型疗法如分子胶降解剂、AAV基因疗法、多肽药物分子、ADC等，这些新药物能解决传统药物难以解决的问题，更具明显疗效和价值。 总之，武田近两年的布局仍然是主要基于其多年来在肿瘤、胃肠道、罕见病和神经等疾病领域所积累的市场销售优势，引进相应的新产品管线，来延续和保持公司的领先优势。在布局疾病适应症上肿瘤已成为重量板块，相关产品数量最多，这也是因为当下肿瘤仍是需求空间最大的疾病类型。在药物类型上新兴技术的引进也是围绕前述疾病类型，可见武田深耕的决心。 编者按： 近年来，武田制药通过不断引进新的药物管线和技术，以应对市场挑战，保持公司的领先优势。在疾病领域方面，武田制药始终围绕上述四大核心业务领域进行布局。在技术引进方面，武田制药注重新兴技术和新型疗法的研发与应用。未来，随着科技的不断进步和市场需求的不断变化，武田制药能否继续保持敏锐的市场洞察力和创新能力？药渡将持续关注。 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 点击下方“药渡“，关注更多精彩内容 100%预防艾滋！吉利德科学创新药物Lenacapavir 3期临床结果喜人 欧洲杯来了！哪些国家最有望夺得“最佳药物管道”奖杯？ 美国Arthrosi公司创新药AR882溶解痛风石，2期临床试验成果亮相2024欧洲风湿病学大会 点击下方关注，聚焦医药创新一手资讯