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A pharmaceutical ingredient that’s been a key component in nasal decongestants for decades is having its efficacy called into question, and the FDA is now weighing whether to change the compound’s regulatory status — potentially leading to many widely used over-the-counter cold and allergy products being pulled from pharmacy shelves. But before the FDA takes any action, it wants to hear what the public thinks. The ingredient, oral phenylephrine, by itself and in combination with other active ingredients, is in decongestants sold under numerous brand names, such as Sudafed and Mucinex. All products containing oral phenylephrine continue to be available to consumers for now. But on Thursday, the FDA proposed an order that would remove oral phenylephrine from its non-prescription drugs guidelines, called the OTC Monograph. The regulator emphasized that this proposed order is due to lack of efficacy, not because of safety. At one time, phenylephrine was rare in decongestants because pseudoephedrine was the preferred active ingredient. But that compound can be made into the methamphetamine. Efforts to curb meth production led to the Combat Methamphetamine Act of 2005, which moved pseudoephedrine-containing drugs behind pharmacy counters. Drugmakers responded by making more products with oral phenylephrine, which is not covered by this law. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Last year, an FDA advisory committee discussed phenylephrine and unanimously voted that current scientific data do not support the ingredient’s efficacy as a nasal decongestant. The committee raised no concerns about the safety of oral phenylephrine when used at the recommended dose. The FDA now says it has conducted a comprehensive review of all available safety and efficacy data for oral phenylephrine as a nasal decongestant, including historical data used to support the compound 30 years ago. Speaking during a conference call with journalists Thursday, Theresa Michele, director of the FDA’s office of nonprescription drugs, said new data had become available since the advisory committee meeting, which the agency also reviewed. “At this point, based on the available data, and taking into account the advice of the advisory committee, we are proposing that oral phenylephrine is not effective to relieve nasal congestion at the recommended dose set forth in the monograph,” Michele said. Phenylephrine is also an ingredient in some nasal spray decongestants. The FDA’s proposal does not extend to such products. The proposed FDA order can be found here. Public comments may be submitted here (use docket number FDA-2024-N-4734 ) through May 7, 2025. After considering the comments, the agency may issue a final order removing oral phenylephrine from its guidelines, which would mean nasal decongestants could no longer contain the compound. Michele said the FDA would then provide manufacturers with time to either reformulate their medicines or remove oral phenylephrine-containing products from the market. Don’t let the autumn sniffles get you down. Here’s a look back at other recent regulatory news, including U.S. and European actions on several novel medications (alas, no new decongestants): Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Decisions for Drugs and Devices —The FDA needs more time to review Organon drug Vtama as a treatment for atopic dermatitis. The company said the regulator has pushed out the December target date for a decision by three months to March 12, 2025. Vtama is from Roivant Sciences subsidiary Dermavant, which Organon recently acquired for $175 million up front. Under Dermavant, the topical drug won FDA approval in 2022 as a treatment for plaque psoriasis. —Novartis cancer drug Scemblix expanded its FDA-approved uses to include the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ PML). The tablet, part of a class of drugs called STAMP inhibitors, initially landed accelerated FDA approval in 2021 as a treatment for advanced cases of Ph+ PML. —The FDA approved Iterum Therapeutics antibiotic Orlynvah. The regulatory decision covers the treatment of uncomplicated urinary tract infections in women who have limited or no oral antibacterial treatment options. The drug, whose main ingredient is sulopenem, is taken as a tablet twice daily for five days. —Astellas Pharma landed FDA approval for zolbetuximab, brand name Vyloy, as a treatment for gastric or gastroesophageal junction adenocarcinoma. It’s the first FDA approval for a drug targeting the cancer protein claudin 18.2 (CLDN18.2). The regulatory decision specifically covers patients whose cancer is negative for a different cancer protein called HER2. Drugs are already available for HER2-positive cancers. —In other Astellas news, the Japanese pharma company withdrew its European Medicines Agency application for geographic atrophy drug avacincaptad pegol. The company said it made the decision after discussions with the agency’s Committee for Medicinal Products for Human Use. The drug, administered as a once-monthly eye injection, won FDA approval in geographic atrophy last year and is marketed in the U.S. under the brand name Izervay. Failure to secure approval in Europe will make it harder for Astellas to recoup the $5.9 billion it spent to acquire Iveric Bio, the company that developed the drug. —Pfizer respiratory syncytial virus vaccine Abrysvo expanded its FDA approval to include adults age 18 through 59, broadening the market for the product. The initial FDA approval of Abrysvo last year covered patients age 60 and older. It’s also approved for use by pregnant individuals as a maternal vaccine; antibodies produced by the mother confer protection against RSV intended to last from the baby’s birth up to six months of age. —Gilead Sciences’ Trodelvy will no longer be available in the U.S. for treating urothelial carcinoma, an aggressive bladder cancer. After discussions with the FDA, the company decided to voluntarily withdraw the product, which had won accelerated approval in this indication in 2021. In May, the company reported Trodelvy failed its confirmatory Phase 3 test in advanced urothelial carcinoma. The withdrawal in urothelial carcinoma does not affect drug’s approved uses in breast cancer. —After previous regulatory setbacks, AbbVie finally landed FDA approval for Vyalev, a Parkinson’s disease drug/device combination product that provides 24 hour subcutaneous infusion of the medications foscarbidopa and foslevodopa. Last year, the regulator turned down the product’s application, asking for more information about the pump in the device. The FDA did not raise any questions about safety or efficacy, nor did it ask for another clinical trial. This past June, the agency again turned down AbbVie’s application for issues at the product’s third-party manufacturer. —There’s a new Pfizer drug for both hemophilia A and B. The FDA approved the antibody drug marstacimab for preventing or reducing frequency of bleeding episodes in patients 12 and older. Pfizer will market the drug under the brand name Hympavzi. As a once-weekly injectable medication, Hympavzi will provide an alternative to IV-infused hemophilia therapies. —The FDA needs more time to review Intercept Pharmaceuticals’ application seeking full regulatory approval of Ocaliva, which had received accelerated approval in 2016 for the rare liver disease primary biliary cholangitis. Intercept, now a subsidiary of Alfasigma, said the agency did not provide a new date for a regulatory decision. —Alzheimer’s disease drug Leqembi hit a regulatory obstacle in Australia, where the Therapeutic Goods Administration decided against registering the medication. Eisai said it will request a reconsideration as permitted under Australian law. It’s the second setback for the drug in recent months. Over the summer, the drug received a negative opinion from a European Medicines Agency committee concerned about the risk of severe side effects and limited benefit. Leqembi has approvals in the U.S., Japan, China, and several other markets. —The FDA approved a Thermo Fisher Scientific companion diagnostic to Voranigo, a Servier Pharmaceuticals’ drug approved over the summer for treating patients whose glioma is driven by mutations to IDH1 or IDH2 enzymes. The diagnostic, called Ion Torrent Oncomine Dx Target Test, identifies patients whose cancer carries the genetic signature making them eligible for treatment with the Servier drug. —Advanced cases of non-small cell lung cancer can now be treated with a wearable device. The FDA approved Novocure’s Optune Lua, a wearable technology that kills cancer cells with electrical signals administered via electrodes placed on the skin. Novocure’s “tumor-treating field” technology was first approved in 2011 as a treatment for a recurrent type of brain cancer. —The FDA rejected Zealand Pharma’s dasiglucagon, a drug developed to prevent and treat hypoglycemia in children who have the rare disease congenital hyperinsulinism. According to the Copenhagen-based biotech, the regulator cited issues at a third-party manufacturer. The FDA did not raise any concerns about the drug’s clinical data or safety. Advisory Committee Outcomes —An FDA advisory committee voted 11 to 3 that the benefits of Lexicon Pharmaceuticals’ sotagliflozin do not outweigh its risks when used as an adjunct to insulin to treat adults with type 1 diabetes and chronic kidney disease. But some committee members expressed support for use of the drug in subpopulations of patients. Sotagliflozin, given the brand name Zynquista, is expected to receive an FDA decision by Dec. 20. Sotagliflozin was approved last year for the treatment of heart failure and is marketed as Inpefa in this indication. —The European Medicine Agency’s Committee for Medicinal Products for Human Use yet again recommended against renewing the marketing authorization for Translarna, a PTC Therapeutics drug for Duchenne muscular dystrophy. Translarna received conditional marketing authorization in 2014. After the drug failed its Phase 3 study, the committee twice recommended against renewing the authorization. The latest opinion comes after the EMA directed the committee to reconsider, taking into account “the totality of evidence.” The committee said its reassessment “concluded that the effectiveness of Translarna has not been confirmed.” —Stealth BioTherapeutics moved a step closer to potential approval of the first drug for Barth syndrome. An FDA advisory committee voted 10 to 6 that Stealth’s drug, elamipretide, was effective at treating the ultra-rare mitochondrial disorder. The committee vote follows several regulatory setbacks, including a 2021 refuse-to-file letter in which the FDA pointed out that elamipretide failed its clinical trial. Stealth maintains there was improvement in a subgroup of patients and the short duration of treatment is the reason for the trial failure. An FDA decision is expected by Jan. 29. What’s New in Covid-19 —The European Commission granted marketing authorization to Novavax’s updated Covid-19 vaccine, Nuvaxovid. Authorization for the protein-based vaccine covers its use in those age 12 and older. The FDA authorized the updated version of Novavax’s Covid-19 vaccine in September. —In other Novavax Covid-19 news, the FDA pressed pause on the company’s plans for late-stage testing of a combination flu/Covid-19 vaccine as well as a standalone influenza vaccine. According to Novavax, the clinical hold stems from a report of motor neuropathy in a single patient outside the U.S. who received the combination vaccine in a Phase 2 study. The trial was completed in July 2023 and the serious adverse event was reported in September. Novavax said previous Covid-19 and influenza trials showed no signs of motor neuropathy. The company’s standalone Covid-19 vaccine is unaffected by the clinical hold. —In Covid-19 and flu testing news, the FDA granted marketing authorization to a Healgen Scientific over-the-counter, at-home test for both pathogens. The OTC Healgen Rapid Check Covid-19/Flu A&B Antigen Test uses a sample from a nasal swab. The authorization covers use of the product by people age 14 and older within five days of the start of symptoms. For children as young as 2, the sample must be collected by an adult.

来源：药渡 撰文：幻目     编辑：维他命 到目前为止，FDA在2024年已经批准了一些重磅新药，包括礼来用于治疗阿尔茨海默病的Kisunla和Madrigal制药公司治疗代谢功能障碍相关脂肪性肝炎的Rezdiffra，以及BMS的35年来第一种新型精神分裂症药物KarXT等。相关拓展：35年来首款！FDA批准BMS新型精神分裂症药物，5款新药紧随其后…… 10月又有一些新药获批，1家公司收到完整回复函（CRL）获批在望，以下汇总了10月FDA一些批准信息。 01 Scemblix 研发企业：诺华 适应症：FDA批准了诺华Scemblix的适应症扩展，用于治疗成人费城染色体阳性慢性粒细胞白血病。 Scemblix是一种口服酪氨酸激酶抑制剂，通过阻断BCR-ABL1融合蛋白起作用，BCR-ABL1融合蛋白是某些白血病的已知标志物。该药物于三年前首次获批用于白血病，赢得了两个适应症。第一个是用于治疗费城染色体阳性的慢性期白血病，该药物获得了加速批准。第二种是完全批准相同的患者群体，并附加他们携带T315I突变。 适应症扩展得到了III期ASC4FIRST研究数据的支持，该研究显示，68%的Scemblix 患者达到临床终点，而接受伊马替尼和尼洛替尼等标准治疗酪氨酸激酶抑制剂疗法的患者为49%。预计Scemblix的峰值销售额将超过30亿美元。 02 Jylamvo 研发企业：Shorla Oncology 适应症：小儿急性淋巴细胞白血病和多关节幼年特发性关节炎 Shorla Oncology获得Jylamvo的扩大批准，用于治疗急性淋巴细胞白血病（ALL）和多关节幼年特发性关节炎（pJIA）的儿科患者。据美国-爱尔兰专业制药公司称，Jylamvo是市场上唯一获准用于成人和儿童适应症的口服液体甲氨蝶呤。 Jylamvo于2022年11月首次获得批准，用于治疗患有急性淋巴细胞白血病、蕈样肉芽肿、复发或难治性非霍奇金淋巴瘤、类风湿性关节炎和严重银屑病的成人患者。 Shorla首席执行官Sharon Cunningham在一份声明中表示：“此次批准是基于Jylamvo在成年患者中成功使用之后，在解决肿瘤学和自身免疫性疾病中儿科护理未满足需求方面向前迈出的关键一步。” 03 Roxybond 研发企业：Protega Pharmaceuticals 适应症：剧烈疼痛 专注于疼痛管理和新型抗滥用产品开发的Protega Pharmaceuticals公司宣布，FDA批准ROXYBOND™ 10mgTablet（盐酸羟可酮速释10mg片剂）用于治疗严重到需要使用阿片类止痛药且替代疗法不足的疼痛。 CDER已经批准了10种具有旨在阻止滥用性质的阿片类产品，但是除Roxybond之外的所有产品都是缓释/长效（ER/LA）制剂，Roxybond是FDA第一个获批的具有防滥用特性的速释（IR）阿片类药物。其采用SentryBond™防滥用技术配制而成，该药物采用多层包衣片剂的形式，通过物理及化学方法屏蔽以防滥用。实验数据显示，与其他速释阿片类止痛药物相比，Roxybond在抵抗切割、挤压、研磨或工具破坏方面有着显著提升。 此外，在多种条件下，Roxybond药片可以抵抗家用或试验用溶剂，从而达到抗化学提取的效果。Roxybond含有的粘性材料还可以使药物难以通过针头进行注射，并且使溶液配制变得更加困难。由此，Roxybond可以很好地阻止经静脉内和鼻内（鼻吸）途径的滥用。除了FDA批准的10mg片剂外，ROXYBOND此前已获批准，目前已有5mg、15mg和30mg片剂。增加ROXYBOND 10mg可增强阿片类药物治疗的灵活性和精确性，旨在帮助医生和患者实现更有效、更安全的疼痛管理。 04 Orlynvah 研发企业：Iterum Therapeutics 适应症：尿路感染 美国FDA批准Orlynvah用于治疗由指定微生物（大肠杆菌、肺炎克雷伯菌或奇异变形杆菌）引起的无并发症尿路感染（uUTIs）成年女性，这类患者没有或几乎没有可替代口服抗菌的治疗方案。根据新闻稿，Orlynvah是FDA批准的首个口服培南类抗生素，也是过去二十年中第二款获得FDA批准的uUTI治疗药物。 Orlynvah的批准得到了两项III期试验的支持。在关键的晚期REASSURE研究中，Iterum的药物在总体反应方面显示出不劣于Augmentin（阿莫西林/克拉维酸）的统计学非劣效性，而在关键的III期SURE1研究中，Orlynvah在喹诺酮类耐药感染患者中的表现优于环丙沙星。在两项研究中，治疗组之间的安全性相当。 05 Abrysvo 研发企业：辉瑞 适应症：呼吸道合胞病毒 在FDA扩大了辉瑞Abrysvo的标签后，患呼吸道合胞病毒（RSV）相关下呼吸道疾病风险较高的年轻人现在有了预防选择。据辉瑞公司称，Abrysvo是第一种可用于50岁以下成年人的RSV疫苗。 Abrysvo在III期MONeT试验中的“推断疗效”支持了标签扩展。根据辉瑞4月份披露的顶线数据，该试验达到了其主要疗效终点，在60岁及以上的年轻人中引发了非劣效免疫反应。 Abrysvo也是妊娠32至36周孕妇的唯一疫苗选择，旨在为从出生到6个月的婴儿提供保护。 06 Vyloy 研发企业：安斯泰来 适应症：胃或胃食管交界处癌 在FDA批准安斯泰来的Vyloy后，某些胃癌患者有了新的治疗选择。据安斯泰来称，获得批准后，Vyloy成为美国第一个针对胃或胃食管交界处癌的claudin18.2靶向疗法。 Vyloy被特别批准用于claudin18.2阳性HER2阴性肿瘤患者的一线治疗，联合含氟嘧啶和铂类化疗。 该批准得到了III期SPOTLIGHT和GLOW研究数据的支持，这两项研究均达到了无进展生存期的主要终点和总生存期的关键次要终点。在这两项研究中，Vyloy的耐受性良好，最常见的副作用包括恶心、呕吐和食欲减弱。 07 Vyalev 研发企业：艾伯维 适应症：帕金森病 随着FDA批准艾伯维的Vyalev作为“第一个也是唯一一个基于左旋多巴的疗法皮下输注用于治疗运动波动”药物，这种新的非手术方案可在早、中、晚持续输送左旋多巴。对于晚期帕金森病（PD）患者来说，有了新的治疗选择。 这一批准主要基于一项为期12周的关键性3期临床试验，该研究评估了Vyalev在晚期PD成人患者中持续皮下输注的疗效，并与口服即释型卡比多巴/左旋多巴进行了对比。此外，还有一项为期52周的开放标签研究，评估了Vyalev的长期安全性和有效性。 关键性临床试验结果显示，接受Vyalev治疗的患者在运动能力波动改善方面表现出更佳效果，与口服药物相比，其运动症状控制较佳的时间增加，运动障碍症状回归的时间减少。在第12周时，Vyalev组运动症状控制较佳的时间增加2.72小时，活性对照组这一数值为0.97小时。 08 Lumryz 研发企业：Avadel Pharmaceuticals 适应症：与儿童发作性睡病相关的猝倒或白天过度嗜睡 Avadel Pharmaceuticals的Lumryz现已获准用于治疗7岁及以上患有白天过度嗜睡（EDS）或猝倒（突然肌肉无力）的儿科患者。 Lumryz是一种睡前服用的缓释羟丁酸钠制剂，最初于2023年5月1日获得FDA批准，用于治疗成年发作性睡病患者的猝倒或过度嗜睡症。Lumryz在成人中的批准基于3期临床试验REST-ON的积极结果。该研究表明，与安慰剂相比，在三项共同主要终点（即维持清醒测试、临床总体印象-改善评分以及每周平均猝倒发作次数）上，Lumryz的效果均具有高度统计学显著性（p<0.001）和临床意义。 LUMRYZ获得儿科使用批准对患有嗜睡症的儿童及其家庭来说是一项重要进展，因为它提供了一种无需半夜服药的一次性睡前治疗选择。FDA的决定得到了临床试验结果的支持，这些结果证明了该药物的有效性和安全性。随着其儿科批准，该药物还获得了孤儿药独占权，有效期至2031年10月16日，为Avadel在未来七年内提供了针对这一患者群体的市场独占权。 09 Hympavzi 研发企业：辉瑞 适应症：血友病A和血友病B FDA批准辉瑞的Hympavzi作为美国第一个每周一次的血友病B皮下预防性注射用药。据辉瑞称，Hympavzi同时被授权用于治疗血友病A，也是第一种通过预装笔或注射器用于治疗两种疾病的方法。Hympavzi旨在用于常规预防，以降低血友病患者出血发作的频率或完全预防出血发作。 Hympavzi的批准得到了III期BASIS试验数据的支持，该试验招募了近190名重度A型血友病或中重度至重度B型血友病患者。在这项试验中，辉瑞药物治疗使得缺乏因子VIII或IX因子抑制剂的患者出血减少了92%，年出血率下降了35%。 相关拓展：重磅首款！每周一次，辉瑞长效血友病疗法获FDA批准 10 dasiglucagon 研发企业：Zealand Pharma 适应症：先天性高胰岛素血症 Zealand Pharma收到了FDA关于达西格列酮（dasiglucagon）新药申请（NDA）第一部分的完整回复函（CRL），该药物用于预防和治疗7天及以上先天性高胰岛素血症（CHI）的儿科患者的低血糖症，最多服用3周。 CRL关注在第三方设施重新检查的时间安排，并没有提出关于dasiglucagon临床数据或安全性的问题。FDA要求从现有的CGM数据集中进行额外的分析，以支持在3周后使用dasiglucagon，Zealand Pharma预计将在2024年底之前提交相关数据。 参考资料： https://www.biospace.com/biospace-fda-decision-tracker *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！ 解决传统PROTACs、miRNA疗法关键挑战，miRiaTAC开启精准抗癌新征程 直击“不死的癌症”红斑狼疮！数百条研发管线能否改写患者命运？ 药企裁员形势严峻依旧 | 十月汇总