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点击上方“蓝字”关注我们吧！ 由四川省预防医学会悉心主办的第七次神经变性疾病防治分会暨西部帕金森防治联盟学术年会，于2024年11月8日在享有 “天府之国” 美誉的成都隆重开幕，并在11月10日落下帷幕。此次学术盛会汇聚了各方智慧，为该领域注入崭新的活力与希望。 11月8日下午，四川大学华西医院商慧芳教授、遂宁市第一人民医院方登富主任，以「帕金森病症状波动治疗药物治疗：新进展」为主题，对帕金森病症状波动的疾病负担与治疗新选择进行了精彩的阐述和深入的分析。 商教授展示了一项横断面研究，在该研究患者数据中，病程≥10年的帕金森病患者出现症状波动的患者百分比高达64.46%1，而中国拥有庞大的帕金森病患者基数（现已超500万2），也就意味着我国帕金森患者症状波动的疾病负担严重。同时商教授指出既往我们最常关注的是运动症状波动，但疼痛、情绪障碍等非运动症状波动的患者比例也较高，提醒我们在对帕金森病患者进行管理时需要关注患者合并的非运动症状的波动，进行全面综合治疗。 商教授分享了即将在中国上市的新药甲磺酸沙非胺，并逐一介绍了沙非胺的药理机制、国内外的临床试验数据等。确切地证实了甲磺酸沙非胺高度契合帕金森病患者的全面综合治疗需求。 1 药理机制 沙非胺是一款同时具有多巴胺能机制和非多巴胺能机制的药物，其作为高度选择性、可逆的B型单胺氧化酶抑制剂，能有效减少已分泌多巴胺在突触间隙的降解，帮助维持大脑中的多巴胺浓度。除此之外，沙非胺还能阻断神经元上电压依赖性钠离子通道，从而抑制谷氨酸的过度释放。 2 国内临床试验 在国内临床试验中，商教授着重介绍了沙非胺的中国Ⅲ期临床试验（XINDI研究）的关键结果，该结果也已于2022年发表在《CNS Drugs》上。此项研究显示沙非胺作为左旋多巴的联合治疗16周后，相比于安慰剂，可明显减少“关”期时间1.1小时（p <0.0001）。除了改善症状波动之外，此项研究中还显示，联用沙非胺之后可进一步减少“开”期状态下的UPDRS Ⅲ（统一帕金森病评定量表-运动检查）评分和PDQ-39评分（39项帕金森患者生活质量问卷），改善患者的运动症状和生活质量3。 3 国际临床试验 在国际多中心Ⅲ期研究中，沙非胺也积累了许多临床获益的证据。沙非胺可显著增加“开”期时间，减少每日“关”期及清晨“关”期时间，减少“开”期状态下的UPDRS Ⅲ评分及PDQ-39评分4；在此基础上，其事后分析显示，沙非胺还可以减少合并有疼痛的帕金森病患者止痛药物使用频次，改善帕金森病患者HAMD（汉密尔顿抑郁量表）评分，并且以上提及的这些临床获益可长期维持5，6，7。 1 间接比较研究结果 商教授最后分享了一项锚定匹配调整间接比较研究结果，这项研究的结果显示，在中国帕金森症状波动患者中，沙非胺作为左旋多巴的联合治疗，与雷沙吉兰相比，可进一步缩短“关”期时间0.7小时（MD= -0.7 , 95%CI: -1.40 , -0.02 ,  p＜0.05）。此外，在改善运动症状UPDRS Ⅲ方面，沙非胺与雷沙吉兰相比，可进一步减少UPDRS Ⅲ（开期）2.9分（MD= -2.9 , 95%CI: -5.28 , -0.52 , p＜0.05），并且在安全性方面无明显差异8。 2 国际帕金森病与运动障碍大会上展示 该项研究结果也由商慧芳教授团队在今年的MDS（国际帕金森病与运动障碍大会）学术会议上展示。这一成果引发了广泛关注，也为帕金森领域带来了新的思路和方向，有力地推动着帕金森领域的临床实践不断前行，促进科学研究持续深入发展，为帕金森病患者带来了更多的希望和福音。 学术专场 总结 本次学术专题会的最后，会议主持方登富主任发言总结，帕金森病中晚期患者会合并各种症状波动，病情复杂，疾病负担较重。帕金森领域迫切需要新的药物出现，而甲磺酸沙非胺作为即将在中国上市的新药，其在症状波动、运动症状的改善，以及疼痛、情绪等在内的非运动症状的控制均有不错的效果，且在改善症状波动及运动症状方面比雷沙吉兰疗效更优。我们相信沙非胺会给患者带来新的曙光。 参考文献 [1] Sun Q, Wang T, Jiang TF, et al. Clinical Profile of Chinese Long-Term Parkinson's Disease Survivors With 10 Years of Disease Duration and Beyond. Aging Dis. 2018;9(1):8-16. Published 2018 Feb 1. [2] Xu T, Dong W, Liu J, et al. Disease burden of Parkinson's disease in China and its provinces from 1990 to 2021: findings from the global burden of disease study 2021. Lancet Reg Health West Pac. 2024;46:101078. Published 2024 May 8. [3] Wei Q, Tan Y, Xu P, et al. The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson's Disease with Motor Fluctuations.CNS Drugs. 2022;36(11):1217-1227. [4] Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D, Stocchi F, Lucini V, Giuliani R, Forrest E, Rice P, Anand R; Study 016 Investigators. Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Mov Disord. 2014 Feb;29(2):229-37. [5] Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt MH, Chirilineau D, Stocchi F, Lucini V, Giuliani R, Forrest E, Rice P, Anand R; Study 018 Investigators. Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease. Mov Disord. 2014 Sep;29(10):1273-80. [6] Cattaneo C, Kulisevsky J, Tubazio V, Castellani P. Long-term Efficacy of Safinamide on Parkinson's Disease Chronic Pain. Adv Ther. 2018;35(4):515-522. [7] Cattaneo C, Müller T, Bonizzoni E, Lazzeri G, Kottakis I, Keywood C. Long-Term Effects of Safinamide on Mood Fluctuations in Parkinson's Disease. J Parkinsons Dis. 2017;7(4):629-634. [8] Y. Tan, Q. Wei, P. Xu, E. Tao, L. Wang, C. Cattaneo, H. Shang, S. Chen. A matching-adjusted indirect comparison of efficacy and safety for safinamide versus rasagiline as adjunctive treatment to levodopa in Chinese patients with Parkinson’s disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/a-matching-adjusted-indirect-comparison-of-efficacy-and-safety-for-safinamide-versus-rasagiline-as-adjunctive-treatment-to-levodopa-in-chinese-patients-with-parkinsons-disease/.Accessed September 28, 2024. 提示：本材料仅供医疗卫生专业人士进行医学科学交流，不用于推广目的。

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.