Clonazepam

MALVERN, Pa., Nov. 18, 2024 /PRNewswire/ -- Endo, Inc. (OTCQX: NDOI) ("Endo") announced today that one of its operating subsidiaries, Endo USA, Inc., is expanding its previously announced voluntary recall of Clonazepam Orally Disintegrating Tablets, USP (C-IV) due to potential product carton strength mislabeling. Continue Reading Carton front and blister pack Carton side Specifically, Endo's ongoing investigation has identified the possibility that the Clonazepam product lots listed below contain a limited number of cartons printed with the incorrect strength and National Drug Code (NDC) code due to an error by a third-party packager. The blister strips and tablets inside the product pack reflect the correct strength for the lot. The following table details the lots being added to the voluntary recall, including lot product description and NDC number. Risk Statement: Children and adults who inadvertently consume a higher dose of clonazepam could be at increased risk for the adverse events of significant sedation, confusion, dizziness, diminished reflexes, ataxia, and hypotonia. There is reasonable probability for significant, possibly life-threatening, respiratory depression especially for patients with concomitant pulmonary disease, patients who have prescribed dosing near maximal dosing, and patients also taking other medications that could cause additional respiratory depression. To date, Endo has not received any reports of adverse events associated with this product recall. Clonazepam Orally Disintegrating Tablets are indicated alone or as an adjunct in the treatment of the Lennoz-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. Additionally, the product is indicated for the treatment of panic disorder. Package Identification: The product is packaged in cartons containing 60 tablets packed into 10 blister strips each containing 6 tablets. The carton and each blister strip pocket are printed with the name, strength, lot number, expiration date, and NDC number. The packaging lists the legacy company Par Pharmaceutical which previously marketed clonazepam before the product was acquired by Endo. The images below provide an example of the potential mislabeling showing the components of a package of Clonazepam Orally Disintegrating tablets, USP 2 mg lot 550176501 with a carton bearing the product description and NDC code of Clonazepam Orally Disintegrating Tablets, USP 1 mg 60-count. The location of the lot number on each component of the package is shown on the photographs within this release. Action Required: The product lots were distributed through wholesale distributors to retail pharmacies nationwide. Endo is providing written notification to wholesale accounts and retailers that have received the product lots and is arranging for the return of all existing inventory through Inmar, Inc. Distributors, retailers that have the product lot being recalled should immediately stop distributing and dispensing and return to the place of purchase or contact Inmar on the below telephone line. Consumers in possession of any unused prescribed tablet cartons of Clonazepam Orally Disintegrating tablets, USP bearing the above lot numbers have been advised to discontinue use of the product. In the event that a patient inadvertently took an incorrect dose rather than the intended dose, they are advised to consult a physician. Consumers with questions regarding this recall can contact Inmar by telephone at 855-589- 1869 (Monday through Friday, 9 a.m. to 5 p.m. ET) or by email at [email protected]. For more information about Clonazepam Orally Disintegrating Tablets, USP, please see full Prescribing Information including BOXED WARNING available at DailyMed - CLONAZEPAM tablet, orally disintegrating (nih.gov). Adverse reactions or quality problems experienced with the use of this product lot may be reported to the U.S. Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program: Online: Mail: use postage-paid, pre-addressed Form FDA 3500 available at Fax: 1-800-FDA-0178 This product lot recall is being made with the FDA's knowledge. About Endo Endo is a diversified pharmaceutical company boldly transforming insights into life- enhancing therapies. Our passionate team members collaborate to develop and deliver these essential medicines. Together, we are committed to helping everyone we serve live their best life. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements including but not limited to any statements related to product recalls, mislabeling, adverse events, FDA or other regulatory actions and any other statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may," "look forward," "guidance," "future," "potential" or similar expressions are forward-looking statements. Because these statements reflect Endo's current views, expectations and beliefs concerning future events, they involve risks and uncertainties, some of which Endo may not currently be able to predict. Although Endo believes that these forward-looking statements and other information are based upon reasonable assumptions and expectations, readers should not place undue reliance on these or any other forward-looking statements and information. Actual results may differ materially and adversely from current expectations based on a number of risks, uncertainties and factors, including risks and uncertainties related to the recall and any future recalls, potential adverse events and any regulatory actions by the FDA. Endo assumes no obligation to publicly update any forward- looking statements, whether as a result of new information, future developments or otherwise, except as may be required under applicable securities laws. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by Endo and in Endo's public filings with the U.S. Securities and Exchange Commission, including the discussion under the heading "Risk Factors" in Endo's most recent Form 10-Q and in Endo's final prospectus filed pursuant to Rule 424(b) under the Securities Act of 1933, as amended, in connection with its Form S-1/A. SOURCE Endo, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

癫痫治疗领域再次迎来重磅交易。 近日，灵北制药宣布以26亿美元的价格，收购Longboard Pharmaceuticals。后者的核心管线是bexicaserin，一款高选择性的5-HT2C超级激动剂，用于治疗难治性癫痫DEE，已完成二期临床并获得突破疗法认证。 收购消息传出后，Longboard股价大涨超50%。年初至今，由于公布bexicaserin 1b/2a期研究的积极顶线数据，其股价一路上涨，涨幅超过888%。 灵北制药是丹麦精神疾病与神经系统疾病领域先驱，也是为数不多专注于CNS疾病的制药公司之一。大手笔收购Longboard，也意味着其在神经学和罕见疾病这片充满挑战却又极具潜力的领域中，更进一步。 尽管失败如影随形，但是，随着越来越多药企尝试征服这一CNS研发高地，或许，正如阿尔兹海默症般，经历数十载漫长黑夜，癫痫药物的开发正在迎来春天。 严重未满足的临床需求 癫痫是最常见的中枢神经系统疾病（CNS）之一，影响着全球5000多万人。作为一种高致残性的慢性神经系统疾病，癫痫以其发作的不可预测性对患者生活造成极大影响。对于患者来说，治疗首选方案是抗癫痫发作药物（ASMs），这也是最基础、最重要的治疗手段。 过去几十年，已有超过20种ASMs问世，从第一代演变至第三代，然而，疗效有限、副作用明显等问题依然影响着癫痫患者的治疗效果，是目前ASMs亟待解决的问题。 比如，第一代ASMs包括苯巴比妥、苯妥英钠、卡马西平、丙戊酸、氯硝西泮等。这些药物在早期的癫痫治疗中发挥了重要作用，但其副作用较为明显，如嗜睡、头晕、恶心等，并且药物之间的相互作用较多，需要严格控制剂量和监测不良反应。 而第二代ASMs如加巴喷丁、拉莫三嗪、托吡酯、左乙拉西坦、普瑞巴林等。相比第一代药物，副作用有所减少，药物间的相互作用也较少，是目前治疗的主流。 但是，在过去的30年中，二代ASMs的广泛使用似乎并未使癫痫药物治疗的整体疗效和耐受性得到提高。近几年上市的三代ASMs，能否打破目前的停滞状态还有待于进一步观察。 与之相比，还有一类患者的治疗困境尤为突出。尽管WHO指出70%的癫痫患者通过ASMs治疗可达到消除癫痫发作，但仍有约30%的患者对现有ASMs不敏感，癫痫发作无法得到有效控制，称为难治性癫痫。 这类患者由于异质性、耐药性导致可选择的药物十分匮乏。典型如全球神经系统疾病负担的第三大元凶——DEEs。这也是灵北制药此次收购布局的领域。 DEEs是一组罕见的神经系统疾病，通常在婴儿期发作，具有难治性癫痫发作和发育迟缓和/或倒退的特征。同时DEEs涵盖了超过25种不同的综合征，包括Dravet综合征（DS）、Lennox-Gastaut综合征（LGS）、结节性硬化症（TSC）、CDKL5缺乏症（CDD）等，其中仅有4种有获批药物。 虽然这些综合征单独被认为是孤儿病，但据估计在美国大约有22万患者受到DEEs综合征的影响。作为一组疾病，其总体发病率达到（0.27～0.54）/1000例新生儿，癫痫发作的影响还伴随到他们的儿童、成年时期，甚至可能导致过早死亡或者避免死亡但留下严重的神经系统残疾。 而在治疗方面，大多数DEE患者采用多种药物联合治疗，并随时间更换药物。然而，几乎所有患者都经历了多次癫痫发作和治疗相关的副作用。 换句话说，DEEs治疗领域存在严重未满足的临床需求，需要更多更好的治疗选择。 潜在破局者bexicaserin 灵北制药此次收购Longboard，看中的就是bexicaserin有成为DEEs领域破局者的潜力。 Bexicaserin是由Longboard研发的新型口服、高选择性、中枢作用的5-HT2C超级激动剂，正在开发用于治疗与DEE相关的癫痫发作，例如Dravet综合征、Lennox-Gastaut综合征、结节性硬化症、CDKL5缺乏症和其他癫痫性疾病。 5-HT是一种重要的脑内神经递质，与神经元的兴奋-抑制平衡密切相关，其受体包含多种亚型。其中5-HT2C受体，是一种G蛋白偶联受体，这也是Longboard一直专注的成药靶点，已被确定为治疗肥胖和其他CNS疾病(如精神分裂症和药物成瘾)的有效药物靶点。 但是，由于5-HT2C受体与其他两个5-HT2亚型(5-HT2A和5-HT2B)具有约50%的序列相似性，因此导致大量药物存在脱靶效应，或因选择性差从而与5-HT2A、5-HT2B结合，产生幻觉和心脏瓣膜病等副作用。 比如2020年获批用于治疗Dravet综合征的5-HT2激动剂Fintepla，其药物标签上有一个黑框警告，该药物的活性成分与瓣膜性心脏病和肺动脉高压的风险有关。 因此，开发高选择性5-HT2C受体激动剂，作为潜在治疗DEEs药物更具前景。 临床前试验已经验证了bexicaserin的5-HT2C受体高选择性以及相比内源性5-HT能诱导更强的细胞反应。与Fintepla相比，bexicaserin对5-HT2C受体的选择性增加，从而减少了与5-HT2A和5-HT2B激动剂相关的潜在不良反应的可能性。 今年1月，Longboard公布了bexicaserin 1b/2a期研究的积极顶线数据，结果显示： 在主要疗效终点方面，在DEE研究人群中，bexicaserin使可数运动性癫痫发作的中位数减少53.3%，远高于安慰剂组的20.8%。另外，Longboard还公布了在DS、LGS和其他DEE亚组中的数据，癫痫发作的中位数降低分别为72.1%、48.1%和61.2%。 这一数据，与此前Fintepla治疗DS的三期临床数据不相上下。而在安全性方面，bexicaserin表现似乎更优。此前Fintepla各组患者经历了至少一次严重TEAE，bexicaserin最常见的不良事件则是嗜睡、食欲下降、便秘、腹泻和嗜睡。 数据公布后，Longboard的股价一路上涨，截至收购消息公布前，涨幅已经接近600%，而年初至今，其股价涨幅超过888%。 7月，bexicaserin获得FDA突破性疗法认定，用于2岁以上DEEs患者的治疗。9月以来，Longboard正式开启了bexicaserin针对DS的Ⅲ期试验。 优秀的临床表现也成功吸引了灵北制药入局，并对其报以厚望，计划在2028年第四季度正式推出，预计bexicaserin全球销售额达到15-20亿美元。灵北制药总裁Charl van Zyl表示，此次收购是“变革型的交易”，将成为灵北神经罕见病的基石，有可能推动未来十年的发展。 癫痫药物的春天来了？ 由于血脑屏障阻碍、致病机制不明、缺乏有效疾病模型等原因，包括癫痫在内的CNS疾病新药研发困难重重。 幸运的是，包括Longboard在内的biotech在不断努力，包括灵北制药、艾伯维、武田等大药企的加入，也在不断增强我们对于征服该领域的信心。去年底，艾伯维宣布以87亿美元收购Cerevel，后者管线较多，其中之一包括Darigabat，用于治疗难治性癫痫和恐慌症，已经进入2期临床。 整体来看，除了前文提及的bexicaserin、Fintepla，还有一些已上市以及很多处于研究中的新型抗癫痫药物。根据DelveInsight公司提供的数据，目前有超过75家药企在开发癫痫药物，在研药物超过90个。 可以说，这些新一代ASMs的研究和开发为癫痫患者提供了更多治疗选择。而去年以来，癫痫领域在基础、临床研究方面取得了诸多进展。 比如加拿大药企Xenon，其核心管线XEN1101是一款新型小分子Kv7.2/Kv7.3钾通道开放剂，主要开发适应症是癫痫和抑郁症。 Kv7.2/Kv7.3电压门控钾通道在大脑神经元轴突周围和轴突上的表达，是一个特别有吸引力的靶点。这些抑制性离子通道在靠近动作电位阈值的神经膜去极化对抗癫痫的过度兴奋起着制约作用，增强Kv7.2/Kv7.3通道开放的药物已被证明能减少癫痫发作。2011年，瑞替加滨被FDA批准为治疗癫痫的抗惊厥药物，但由于存在严重的皮肤及视网膜色素沉积等毒副作用，已经退市。 与之相比，XEN1101有更高的体外和体内活性，瑞替加滨需要每天给药三次，而XEN1101每天给药一次，且没有色素沉积等问题。临床二期数据显示，XEN1101高剂量组癫痫发作频率相比基线降低52.8%，而安慰剂组只有18.2%。 国内方面，上海药物所研发的派恩加滨同样瞄准这一靶点。而与瑞替加滨相比，派恩加滨的化学性质、活性、药代和安全性特征均显著优化，没有色素沉积风险。临床一期试验证明其具有良好的安全和代谢特性，目前出于二期阶段。 再比如，Epidiolex是一种首创运用大麻成分的抗癫痫疗法，也是首个获批用于DS的药物，其主要成分大麻二酚（CBD）是一种多靶点分子，被证实具有明显抗癫痫活性。 不过，CBD抗癫痫作用的分子机制仍不清楚，其可能的治疗靶点包括离子通道、转运体和跨膜信号蛋白，具体抗癫痫作用的机制仍有待研究。而最新研究显示，LPI-GPR55信号传导通路是CBD抗癫痫靶点的潜在调节因子，在联合用药方面，CBD也为对GABAAR调节剂（例如苯二氮卓类药物）无效的难治性癫痫患者提供了一种潜在的治疗选择。 而在新机制研究方面，武田制药8.65亿美元收购而来的胆固醇24羟化酶（CH24H）抑制剂soticlestat，属于一个全新的抗癫痫作用机制，是通过抑制CH24H活性，减少胆固醇转化为24S-羟基胆固醇，从而降低谷氨酸能通路的兴奋性，减少癫痫发作。 积极的二期试验结果为DS和LGS患者提供了新的药物选择的可能性，尤其是那些对现有药物不敏感的患者。然而，三期试验双双折戟。 总体来看，目前在研治疗方法主要针对遗传学、离子通道和其他神经递质，以及其他潜在性FIC干预措施，比如干细胞、肠道微生物组、AAV9基因疗法等在进行早期研究，也为患者带来了更多新希望。 从趋势来看，癫痫新疗法的研究不再局限于发作的控制，而是包括从发病机制的根源上改变癫痫发作的治疗及预后情况。 总结 需要承认的是，尽管新的突破每天都有可能发生，但这尚无法彻底改变CNS疾病新药研发的困境。 就在上半年，一些药企在研癫痫新药遭遇失败。4月份，Addex宣布ADX71149在治疗对左乙拉西坦或布瓦西坦反应不佳的局灶性癫痫发作的2期研究失败；6月份，Marinus公司口服抗癫痫药物Ztalmy的静脉制剂ganaxolone治疗难治性癫痫持续状态开展的试验失败；武田的soticlestat，在治疗LGS及DS这两种难治性癫痫综合征的三期试验均未达主要终点； 对此，武田表示，在16周的治疗中，治疗应答率、护理人员和临床医生对病情改善的总体印象以及癫痫发作强度和持续时间尺度都发生了显著变化。总体数据呈积极趋势，希望与监管机构商讨下一步行动。 在号称“研发黑洞”的CNS领域，也的确需要武田这种屡败屡战的精神。 期待新的革命性突破，早日到来。