Letermovir

March 12, 2025 -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today presented promising findings from a study exploring how treating asymptomatic cytomegalovirus (CMV) in people living with HIV may improve immune function and physical health. The results from study A5383 were shared as the oral abstract, “Asymptomatic CMV Suppression with Letermovir Improves Immunologic and Functional Aging-related Outcomes in Treated HIV” at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, California. CMV is a common virus carried by most adults and 95 percent of people living with HIV. Before the introduction of effective antiretroviral therapy (ART), CMV often led to life-threatening conditions in the eyes, brain, and gut in individuals with advanced HIV. While ART has dramatically reduced these cases by strengthening the immune system, CMV can still affect immune function and contribute to inflammation, even in the absence of noticeable symptoms. Letermovir is a medication that has been approved by the Food and Drug Administration (FDA) to prevent CMV infection and disease in people who have received transplants. “This is an important finding and ACTG is especially excited because there are currently no interventions that improve immune recovery and functional status in people living with HIV who are taking effective antiretroviral therapy,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “Larger studies are needed to confirm these results; if they do, this intervention could represent a significant breakthrough in HIV and aging research.” A5383 study was a phase 2, randomized, open-label trial designed to assess whether letermovir could reduce inflammation and improve immune recovery in people living with HIV on ART who were CMV-positive but without detectable HIV in their blood. Participants were randomly assigned to either receive letermovir daily for 48 weeks or no CMV treatment. Although an early analysis initially showed a temporary increase in inflammatory markers, continued treatment led to sustained reductions in inflammation and improvements in immune and physical function. Today’s presentation demonstrated that treatment with letermovir led to a significant increase in CD4 counts, with the most pronounced benefits seen in women and individuals whose CD4 T cells remained persistently low. Additionally, those receiving letermovir showed improvements in their CD4/CD8 ratio (a marker of immune system dysregulation that is associated with heart disease, cancer, and mortality in people living with HIV and in elderly populations) and physical function, including an enhancement in chair rise performance (a marker of leg strength and mobility). In addition, improvements in physical function with letermovir correlated strongly with the immunologic improvement observed, suggesting that these beneficial effects were closely linked. “Our team has been working for the last 20 years to address the accentuated aging and premature mortality seen in people living with HIV despite modern treatment,” said Sara Gianella, M.D., Co-Chair of study A5383, University of California San Diego. “We are particularly intrigued to see that it appears that immunologic improvements were greater in women, because in the setting of HIV, women have more inflammation than men, and a greater ‘life expectancy gap’ compared to the general population. These data may also have important implications for the role of CMV in other settings outside HIV, like the elderly and transplant recipients, where CMV has been hypothesized to play a role in long-term health outcomes.” A5383 was led by Dr. Gianella and Peter Hunt, M.D., University of California San Francisco (Protocol Chair). ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice-Chair). It is sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. Study drugs were supplied by Merck & Co., Inc, Rahway, N.J., USA. ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. The content above comes from the network. if any infringement, please contact us to modify.

近日，默沙东一款抗病毒新药的新剂型在国内递交上市申请并获得受理，因适应症囊括药物短缺的儿童用药市场，引发行业关注。 全球范围内，儿童药产品短缺一直是待解的难题，在我国儿童药物市场亦被认为是一片蓝海，市场规模已达千亿。 近几年来我国接连出台政策鼓励儿童药物的研发创新并有意加快相关药物的审评审批，刚过去的2025全国两会上，有代表提及要加大儿童罕见病药物的研发速度以及集采范围，解决相关药物短缺难题。 在此节点，默沙东的儿童新药或将被纳入优先审评，并借此快速切入这一千亿市场，打开新的增长空间。 2024年默沙东旗下K药虽顺利卫冕“药王”宝座，但即将到来的专利悬崖始终如悬颈利剑，加之HPV疫苗这一曾经的大爆品也开始“失灵”，2024年中国区收入跌去两成，整体业绩承压。无论是此次加码儿童药市场还是近两年砸下数百亿在ADC、GLP-1等赛道大力扫货，都意味着，寻求新的业绩补缺者，已成为这家MNC巨头的当务之急。 01 加码儿童药市场 默沙东的来特莫韦，为一种创新型巨细胞病毒末端酶抑制剂，早在2017年已获美国FDA批准上市，是全球首个获批用于异基因造血干细胞移植受者预防巨细胞病毒（CMV）感染的药物。 2022年初该药获批进入中国市场，但剂型主要为适用于成人的片剂和注射剂，此次拟上市的是一款适合儿童的小剂量制剂，直径不超过4mm的来特莫韦微片，适应症除了接受异基因造血干细胞移植（HSCT）的巨细胞病毒（CMV）血清学阳性的成人，还有6个月及以上且体重≥6kg的儿童受者[R+]预防巨细胞病毒感染和巨细胞病毒病。 这也是来特莫韦首次将儿童纳入适应症人群，基于目前巨细胞病毒感染率高，且儿童用药选择不多，未来该药物有望避开仿制药的围剿，并打开新的市场空间。 据悉，2024年来特莫韦国内销售额已近2亿元，三年累计销售额近4亿元。3月8日获CDE受理其上市申请前，该药已在3月4日被公示拟纳入优先审评，理由是来特莫韦微片属于儿童新品种，符合相关政策的要求。 国元证券此前曾有报告指出，2016-2021年，中国儿童药市场规模已由650亿元增长至1080亿元，年均复合增长率为10.69%。另一组数据则显示，儿童药在我国药物总量中比例不足10%，而化药在我国儿童用药市场中占比六成，但其中儿童专用化药仅占5%左右，其余90%以上均为儿童及成人兼用的化药，儿童专用药短缺状况尤为突出。 由于较成人药物的研发困难更大，周期更长，儿童药品市场长期存在着“品种少、剂型少、规格少、特药少”的问题。为此近几年我国陆续出台了鼓励儿童药物研发、提速审评审批、支持生产等多项政策，希望逐步改善临床供应短缺等问题。 2016年至2024年，国家卫健委先后制定发布了5批《鼓励研发申报儿童药品清单》，共计32个儿童适用药品获批上市，包括16个罕见病用药，并明确表示将继续加大儿童用药研发生产各项政策的倾斜力度。 在相关政策及用药需求的推动下，儿科市场未来将迎来更大的发展机遇，行业分析称，预计到2030年，中国儿童用药市场规模将达到1500亿元。 聚焦到默沙东拓展新适应症的来特莫韦微片，成人及儿童巨细胞病毒感染率都较高，其中一岁幼儿的感染率高达80%左右，虽然大部分没有症状，却可以长期潜伏，一旦发病，便可能会对多个器官造成影响，因此临床需求颇大。 默沙东并非第一次涉足儿童用药，此前已有儿童哮喘孟鲁司特钠、儿童抗真菌感染的诺科飞等多款药物均已在国内上市，此番加码中国儿童用药市场，也有望在一定程度上弥补HPV疫苗市场后劲不足带来的业绩“价差”。 02 巨头的业绩保卫战 由于K药的专利悬崖将在2028年到来，默沙东近几年一直在加大力度寻找新的潜在“药王”，但屋漏偏逢连夜雨，前几年爆火的王牌产品HPV疫苗也开始遇冷，令这家MNC巨头中国业绩大跌，整体营收增长承压。 今年2月份默沙东披露的2024年财报显示，在去年整体营收同比增长6.74%至641.68亿美元的情况下，中国区的营收却下滑20%至53.94亿美元，中国市场占全球制药业务的份额，也从2023年的12.5%下降到9.4%。 背后原因便是市场大环境影响，加上消费需求疲软，国产疫苗冲击，渠道库存高，HPV疫苗佳达修第四季度销售同比下滑了17%，全年同比减少3%，因此默沙东在宣布自今年2月份起至年中暂停向中国供应该疫苗后，一度受到行业的热议。 事实上，自2023年HPV疫苗逐渐出现消费需求下滑态势后，默沙东已经开始采取补救措施，一方面开拓HPV疫苗男性市场，一方面加快21价肺炎疫苗等其他产品的上市，但就目前来看，成效尚不明显。 放大至整个企业层面，如果说HPV疫苗是中国市场的最大支撑，那么药王K药无疑是默沙东的门面担当，HPV疫苗的受挫主要影响区域市场，但一年贡献了近300亿美元收入的K药专利悬崖一旦到来，对整体业绩的触动程度可想而知。 为保全球地位，默沙东的“未雨绸缪”动作其实也早已开始。 2019年的JPM大会上，默沙东就特别强调会通过BD交易搭建平衡性更强的管线布局。此后不管是肿瘤还是自免、代谢领域，默沙东都砸下了重金扫货，先后将ADC、GLP-1、PD-1/VEGF双抗等多款热门赛道的管线纳入麾下。 ADC领域，默沙东2020年到2024年累计达成了7笔相关的收购、合作交易，交易总额高达400亿美元。 从科伦博泰、第一三共等同行手中，默沙东拿到了数个ADC项目，目前已有靶向HER3、B7H3、CDH6、TROP2等靶点的ADC药物在研，且已有4个项目处于Ⅲ期临床，1个在申请上市。 为扩大K药的市场，默沙东还在推进K药与旗下ADC药物的联合疗法，今年初K药与Nectin-4 ADC维恩妥尤单抗的联合疗法就在国内顺利获批上市。 在千亿美元市场规模潜力的GLP-1赛道，默沙东同样下了重注，甚至寄予了“药王”继任者的厚望，毕竟准药王司美格鲁肽已经验证了该赛道的潜力。 最早在2010年默沙东就已经有GLP-1项目登记进入临床，此后陆续布局有GCGR激动剂、GLP-1R/GCGR双重激动剂等5个项目，既有自研亦有外部引入，但其中3个均未能走至最后。 2024年，默沙东多次出手收购中国管线资产，先是以5.88亿美元首付款拿下礼新医药的PD-1/VEGF双抗LM-299，随后又以20亿美元的总交易额，引入翰森制药的口服小分子GLP-1受体激动剂HS-10535，开始差异化布局减重赛道。 03 结语 在“钞”能力的加持下，默沙东的补货行动令潜力管线大增，对于“如何面对K药专利悬崖”这一魔咒般的问题，也显得更为从容。 2025年开年的JPM大会上，默沙东首席执行官Rob Davis透露，2024年默沙东的III期在研产品数量相比于2021年几乎翻了两倍，并且在BD交易上前后投入了约400亿美元。默沙东预计，2025年全球销售额将在641亿美元至656亿美元之间。 基于现有肿瘤管线的业务，默沙东还将2030年的肿瘤业务收入目标从200亿美元调高至250亿美元，并计划在未来几年陆续推出20款潜在的重磅药物。 一方面寻求开拓K药更多的市场，另一方面基于多元化的考虑布局多领域药物管线，从而弱化整体收入对K药的依赖，默沙东的多面开花战略，有待未来的市场考验结果。 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 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。