Armodafinil

– 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

首次获批五年后，Austedo有望迈进“重磅炸弹”的行业。而这样一款首创的氘代药物，来自被长期视为仿制药巨头的Teva。不得不说，这是一个意味深长的关联。不同于从靶点开始的源头发现，氘化（即氘代）的方法瞄准的是已上市药物，旨在增强后者的某些性能，例如，通过延长半衰期，增加系统暴露，氘化化合物可以获得更高的安全性、有效性、耐受性和便利性。如果我们把创新大体分成两类，那么，Austedo代表的就是“从1到100”。2022年，Teva以近150亿美元的营收，位列全球仿制药企第二。但看似风光的地位，已经变得不那么可期。仿制药业务的剥离整合运动正在上演，经过长年累月的并购，Teva原来的基本盘也开始显出颓势。创新药，不得不做了。缺乏深厚积累的Teva，在这方面选择小步快跑。氘代药物就是策略之一。此外，随着新任首席执行官Richard Francis的掌舵，Teva对于把握创新机遇也更为热切。“我对这个季度很满意。”Francis在最近的一次采访中表示。2023年第三季度，Teva季度净营收38.5亿美元，较2022年同期增长7%。Teva连续两个季度都取得了收入增长，打破了此前收入连年下滑的尴尬处境。今年5月，刚执掌Teva不久的Francis提出了“Pivot to Growth”战略，目标是加强创新，实现增长，主要由Austedo和Ajovy等药物以及生物仿制药组合驱动。如今半年过去，这一战略成效不错。但是，对于真正的创新转型显然还不够。Teva手头仍有子弹，只是它们都维持在一个“刚刚好”的门槛——稍不留神，就会被甩在身后。并且，对于产品线的布局，Teva的创新似乎也尚未建立起某种特定赛道上让人目不转睛的成就。在第二次跨越式增长之前，前述问题，都是这家想要告别“只有仿制药”之名的巨头所面对的栅栏。1“Pivot to Growth”初现成效2023年第三季度，Teva营收中季度归属公司的净利润是8000万美元，上年同期为5600万美元。Teva将这一增长除了归功于仿制药业务的持续增长外，也特别指出其品牌药物Austedo（Deutetrabenazine）和Ajovy（Fremanezumab）的增长势头。Austedo是全球批准的首个氘代药物。在美国，Austedo于2017年4月获得FDA批准，用于治疗与亨廷顿病相关的舞蹈病。同年8月，FDA批准了Austedo的新适应症，治疗成人迟发性运动障碍。在中国，Austedo于2020年5月获得NMPA批准上市，并于2020年12月被正式纳入国家医保目录。而治疗偏头痛的药物Ajovy，则是在2018年9月获得了FDA的批准。Ajovy的活性成分为靶向CGRP（降钙素基因相关肽）的全人源单抗fremanezumab，是FDA批准的第二款抗CGRP偏头痛新药。2022年Teva的财报显示，Ajovy销售额为3.77亿美元，Austedo创收9.63亿美元，二者同比增长均为20%。今年的三季度报显示，仅在北美地区，Ajovy和Austedo前三季度的销售额分别为1.68亿美元和8.17亿美元，同期增长分别为18%和32%。Ajovy和Austedo稳定且持续的增长给了Teva巨大的信心。目前，Teva预计2023年全年营收将控制在151亿至155亿美元之间，较之前的估计区间均增加1亿美元。在Francis看来，这些成果是“Pivot to Growth”战略正在奏效的早期迹象。这项战略旨在通过加速强大的创新药物组合恢复增长，扩大创新管线专注于具有一流和一流机会的核心治疗领域，维持仿制药地位并将业务集中在最具增长潜力和对患者影响最大的领域。Francis在发言中表示，Teva的新战略建立在4个关键支柱之上，他们将从商业产品组合与生物仿制药、创新管线、仿制药和集中资本配置中实现短期和长期的增长。作为该战略的一部分，Teva今年早些时候宣布将分离其API业务。Teva在最近的一份新闻稿中表示，从11月27日开始，R. Ananthanarayanan （Ananth）将领导API业务，Ananth曾于2014年至2018年领导Teva API和生物制剂运营。2并购，从仿制到创新一直霸榜在全球制药20强左右的Teva带着“仿制药”横冲直撞，凭借强悍的并购整合与海外拓展能力讲述着另一种成长故事。Teva起源于并购，由S.L.E、Teva和Zori三家公司合并而成。1935年，Gunter Friedlander在耶路撒冷创办了Teva。随着更多的科学家、富人回流，以及以色列建国后政府对医药公司的税收补贴，Teva公司发展迅速，并于1951年在特拉维夫挂牌上市。1976年，由Assia和Zori“联姻”的Assia-Zori与Teva进行了合并，如今的Teva就此诞生。随后，Teva就开始了他的收购扩张之路。成立之初就先后收购了Orphahell的荷兰原料药厂、以色列第三大药企Ikapharm。其仿制药销售可追溯至1985年，Teva与特种化学品生产企业W.R.Grace成立的合资企业TAG Pharma收购了Lemmon，并成为Teva在美国的仿制药销售部门。1987年，Teva在纳斯达克公开上市，此后攻势更加迅猛。以色列第二大药企Abic、英国的第二大仿制药公司Approved Prescription Services/Berk、匈牙利仿制药巨头Biogal和美国仿制药公司Biocraft Laboratories，都悉数被Teva纳入麾下。2000年之后，Teva收购的仿制药公司更是数量惊人，其中不乏数百亿的交易。到2017年底，Teva的仿制药销售额已经达到122亿美元，成为全球处方量最大的药企。然而，时局总是生变，“仿制药称王”的世界逐渐成为历史。而如今的Teva，在面对艾尔建、山德士等仿制药巨头时也略显吃力，转型迫在眉睫。Teva的创新药布局可以追溯到上世纪八十年代，1987年，Teva从以色列魏茨曼研究所收购了Copaxone（格拉替雷）的开发权，1996年末，Copaxone获得FDA批准用于多发性硬化的治疗。2005年，Copaxone迈入重磅炸弹行列。多年来，Teva的核心收入都依赖于这款产品，Copaxone一度贡献了其专利药收入的一半左右，年销售额峰值达43.3亿美元。Copaxone之后，Teva又通过收购分别获得了第二代单胺氧化酶抑制剂Azilect（雷沙吉兰）和Nuvigil （阿莫达非尼），但这两款药物的市场表现平平。之后的创新药收购“高光”发生在2014年和2015年，Teva收购Labrys和Auspex获得了如今的主要收入增长药物Ajovy和Austedo。经过30多年的铺陈，Teva的创新药业务渐成气候。3下一个增长点Teva的创新能力其实不容小觑。2014年到2017年间，Teva专利药收入每年都在80亿美元左右，占公司总盈利的53.7%以上，而仿制药收入仅占比20%左右。这次“Pivot to Growth”战略聚焦创新药物，专注于神经科学、自身免疫疾病和肿瘤的核心治疗领域，并将自免药物放在了核心增长位置。Teva表示，自身免疫疾病药物TEV-48574（TEV'574）是未来贡献销售增长的重要力量。10月初，TEV'574刚为Teva带来一笔收益。10月，赛诺菲与Teva就后者在研的用于治疗炎症性肠病（IBD）的TL1A单抗TEV'574达成了共同开发的合作协议。根据协议，Teva将获得4.6亿欧元（约5亿美元）预付款，以及最高达9.4亿欧元（约10亿美元）的里程碑付款。两家公司将平均分担TEV'574全球开发成本以及主要市场的净利润和亏损。Teva将主导TEV'574在欧洲、以色列和其它特定国家的商业化，赛诺菲将主导TEV'574在北美、日本、亚洲其它地区和世界其它地区的商业化。TEV'574最初是Teva为了治疗哮喘而开发的，但该公司在中期研究结果不尽人意，Teva随后停止了试验。不过，考虑到在临床前观察到的效力和选择性，Teva选择开展该产品在治疗疗溃疡性结肠炎（UC）和克罗恩病（CD）的临床II期研究，预计2024年下半年公布中期数据。目前TL1A的赛道还不算拥挤。处在领先位置的有默沙东的PRA023、Telavant/辉瑞合作开发的RVT-3101，这两款产品均已进入临床II期阶段；此外，安进的TL1A/TNF-α双抗AMG966，辉瑞的TL1A/IL12双抗PF-07261271也已进入I期临床。不过，Teva认为自家的药物具有一定的优势。根据Teva的说法，TEV'574在更多细胞上阻断了TL1A蛋白，并且没有结合到清除TL1A的相关蛋白质。Teva还在开发该药物的皮下剂型，而竞争对手是静脉注射剂型。另一款创新重点是奥氮平赖（olanzapine LAI，代号TEV'749）。11月13日，Teva表示已获得Royalty Pharma提供的1亿美元资金，用于支持奥氮平赖（olanzapine LAI）的临床开发，这是礼来精神分裂症药物Zyprexa的长效版本。根据礼来的财报，Zyprexa去年的营收为3.37亿美元，同比下降22%，如今礼来已经出售了该产品。Teva的这款长效版本未来的表现还需时间给出答案。目前，TEV-'749已处在临床III期阶段。TEV-'749为每月一次的皮下注射，相比之下，Zyprexa是每天口服一次。还有一款长效奥氮平注射剂（Zyprexa Relprevv），可通过肌内注射给药，最多每4周给药1次。但该长效版本的深度穿透性为其带来了注射后谵妄/镇静综合征的加框警告。Teva公司认为其制剂的皮下给药可以避免这个问题。未来，Royalty Pharma这笔1亿美元的资金可能会增加到1.25亿美元。作为交换，如果这款药物获得了FDA的批准，Teva将在五年内偿还这笔费用。此外，Royalty Pharma还可以根据药品的销售情况获得一定比例的收入。Teva最近加速了TEV-'749的III期试验，并预计在2024年下半年公布数据。参考文献：1、Teva draws $100M from Royalty funding to bankroll long-acting schizophrenia drug；fiercepharma2、Half a year later, Teva's 'pivot to growth' strategy appears to be bearing fruit；fiercepharma3、Teva（Teva）发家史：30年仿制药出海战中的成功与失败；药事纵横识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。