Seasonal influenza virus vaccine high dose (Sanofi Pasteur)

Introduction前言2024年2月22日，Moderna报告了2023第四季度及财年财务业绩。Moderna首席执行官Stéphane Bancel在电话会议上表示，“2023年是Moderna转型的一年，因为我们适应了季节性市场。与此同时，我们的研发团队在传染病、肿瘤学和罕见病方面取得了重大进展，而我们的商业团队增加了我们在美国的新冠疫苗市场份额。我们期待RSV疫苗在今年上半年初获得监管批准。随着2024年即将报告的多个3期临床项目数据，我们将继续专注于商业执行，并继续以财务合规合序的方式对有希望的管线进行投入。”Moderna在2023第四季度实现盈利，净利润为2.17亿美元，达到每股0.55美元，而分析师曾预计每股亏损0.97美元，这令投资者感到惊讶。其周四股价应声上涨9%。Moderna 2023财报数据转型之年Moderna的报告主题围绕自去年三季度延续至今的战略转型。一是将战略重心从新冠疫苗的生产销售转向其他研发中的临床后期mRNA产品；二是新冠疫苗生产规模、方式也将从大流行过渡向季节性疫苗市场。据Moderna称，其转型计划涉及缩减生产合作方的产能和投入，重新评估其原材料库存，并减少预期在使用前到期原材料的采购。第四季度报告“如预期般”产生了1.69亿美元的额外费用。随着大流行疫苗市场需求的急剧下滑，新冠疫苗减记已成为Moderna及辉瑞的主要应对措施。早在2023年第三季度，Moderna就因新冠疫苗库存“过剩过期”而大幅度减记13亿美元的库存，此外还支付了6亿美元用于制造合同的终止。相比之下，辉瑞在同一时间也产生了56亿美元的相关库存减记和合同终止费用。GlobalData的制药分析师Kevin Marcaida指出，两家公司都试图维持新冠疫苗的收入，但增加了销售价格。“为应对市场需求减弱和COVID-19私营化，辉瑞公司已将Comirnaty的价格翻了两番，现在价格为每剂120 美元。同样，Moderna已将Spikevax的标价定为每剂129美元，这是提高盈利能力的战略举措。”不过在周四的报告中，Moderna重点提到了其在美国市场份额的增长。在整个秋季疫苗接种季节，Moderna新冠疫苗Spikevax的美国市场份额一举从2022年的37%增长到了48%，第四季度营收28亿美元，超过分析师早前预期的25亿美元。Spikevax全年销售额达到了67亿美元，而另一边辉瑞/BioNTech Comirnaty的全年销售额为112亿美元。两家公司新冠疫苗销售额均下降了超60%，而相比之下Moderna的下降幅度较小。在电话会议上，Moderna再次预估2024年的销售额将达到40亿美元，研发成本将达45亿美元。分析公司Third Bridge全球医疗保健部门负责人Lee Brown表示，“我们赞赏Moderna重新定位Spikevax市场的举措。调整生产规模，向季节性市场过渡并扁平化商业结构能够让Moderna对其他有希望的管线进行更多投资。”另一方面，Moderna已花费了数千万美元支持其癌症疫苗的商业化进程，目前已开始在马萨诸塞州马尔堡建立其最近收购的生产工厂，并计划在未来继续扩建。Moderna在新闻稿中表示，该项目用于推进公司与默沙东合作的个性化新抗原肿瘤疫苗mRNA-4157/V940的商业规模生产，总投资预计至少将达到3.22亿美元。“转型”年之后Moderna和投资者已将注意力转向更加“诱人”的临床后期项目，包括呼吸道合胞病毒（RSV）疫苗和巨细胞病毒（CMV）疫苗。周四电话会议上，投资者问题最主要集中在RSV疫苗上。目前该疫苗正在等待FDA于5月份做出决定，加入于葛兰素史克（GSK）Arexvy与辉瑞Abrysvo的市场竞争中。Moderna预计RSV市场将蓬勃发展至100亿美元，老年群体销售额将在60亿至80亿美元之间。在2月8日发表的Moderna mRNA-1345长期随访数据中，在8.6个月时针对两种或更多症状的RSV相关呼吸道疾病的总体保护率为63.3%，远低于3.3个月时的84%，被质疑是否其长期保护效力的减弱速度快于GSK Arexvy 。该数据一经发布，导致Moderna股票下跌9%。然而，随访数据与GSK的Arexvy比较并无法准确看出两者的保护效力有明确差距：Arexvy显示出82.6%的总体保护效力，但在接种后第二季度下降至77%，两季度累积疗效为67.2%。而辉瑞（Pfizer）的Abrysvo在两个季节的疗效从66.7%下降到49%。分析师回应称，从长远来看，Moderna是一个日益增长的威胁。“我们认为，Moderna的mRNA-1345具有非常好的安全性和有效性，但由于其进入市场较晚，因此在上市初期可能处于不利地位。然而，未来Moderna或可能通过RSV的联合疫苗获得市场领导地位。从长远来看，Moderna凭借mRNA技术平台可能会取得最大成功。”Moderna总裁兼研发主管Stephen Hoge博士在电话会议上表示，团队对临床数据感到非常兴奋，并将RSV疫苗mRNA-1345的耐久性描述为“相当令人鼓舞”。他预计CDC将不会对三款RSV疫苗提供不同的管理建议，因为这些产品各方面数据都极为相似。公司对消费者早期迹象和对RSV市场的既定需求感到鼓舞，Moderna将以强大的竞争地位、强大的疗效数据、完善的安全性和耐受性进入该市场，并成为上市时唯一可用的预充式注射器（PFS）产品。PFS即用型制剂将节省药剂师和临床医生的时间，并可能有助于减少给药错误。mRNA-1345的PDUFA（处方药用户费用法案）行动日期为2024年5月12日，届时公司预计美国FDA将对其生物制品许可申请（BLA）作出回应。如果结果是积极的，公司预计美国疾病预防控制中心免疫实践咨询委员会（ACIP）将把mRNA-1345列入其6月26日至28日的会议议程。假设相应的上市许可将按预期获得批准，根据监管审批时间，公司还计划于2024年在澳大利亚和德国推出其RSV疫苗，并于2025年在其他市场推出。此外，Hoge博士预计2024年还将迎来Moderna CMV疫苗mRNA-1647的首批分析数据。根据目前进度，该研究将有足够多病例支持加快启动第一次中期分析。“我们非常有信心能够在近期得到中期分析的数据，甚至可能在2024年内完成疗效的终末分析。”相关阅读：Moderna巨细胞病毒mRNA疫苗，编码五聚体蛋白，你准备好接种了吗？Moderna在2021年就着手开始mRNA-1647的III期临床研究（NCT05085366），该项目被公司称为“CMVictory”，首次在全球范围内进行，预计完成时间为2026年。CMVictory旨在评估100μg剂量的mRNA-1647针对16-40岁女性原发性CMV感染的安全性和有效性。初步的临床试验结果表明，mRNA-1647可成功触发gB/PC特异性的抗体反应。无论血清状态如何，mRNA-1647在接种者中均表现出良好的安全性和耐受性。即将迎来里程碑的后期管线呼吸道疫苗呼吸道合胞病毒（RSV）疫苗：Moderna已向监管申请批准该疫苗，用于预防60岁或以上成年人的RSV相关下呼吸道疾病（RSV-LRTD）和急性呼吸道疾病（ARD）（mRNA-1345）。公司预计将于2024年上半年获得监管部门的批准。Moderna将以强大的竞争优势进入RSV市场，成为上市后唯一的预充式注射器产品。该产品拥有强大的疗效数据、完善的安全性和耐受性。下一代COVID-19疫苗：Moderna的下一代COVID-19疫苗（mRNA-1283）目前正处于关键的3期研究阶段，该产品主打储存方式上的改良，可在冰箱温度下稳定储存。预计将于2024年上半年发布该临床研究的数据。季节性流感疫苗：Moderna的季节性流感疫苗（mRNA-1010）在三项3期试验中表现出一致可接受的安全性和耐受性。在最近的3期试验（P303）中，mRNA-1010达到了所有免疫原性终点，与目前获得许可的疫苗相比，显示出更高的滴度。在另一项1/2期研究中，与目前获得许可的高剂量疫苗（Fluzone HD®）相比，mRNA-1010的滴度也更高或相当。Moderna正在与监管机构进行讨论，并计划2024年提交上市申请。季节性流感+COVID联合疫苗：Moderna针对季节性流感和COVID-19的联合疫苗（mRNA-1083）的3期试验已完成全部入组。公司预计将于2024年获得该研究的数据。潜伏感染疫苗和其他疫苗巨细胞病毒（CMV）疫苗：Moderna的CMV候选疫苗（mRNA-1647）的关键3期研究已完成全部入组，将评估其在预防育龄妇女原发感染方面的疗效、安全性和免疫原性。公司预计该研究的潜在疗效数据将在2024年公布。肿瘤疫苗个性化新抗原疗法（INT）：Moderna将继续验证其INT项目（mRNA-4157）的潜在临床益处。与默沙东公司合作中的3期试验继续招募切除的高危（III/IV期）黑色素瘤和完全切除的II、IIIA或IIIB期非小细胞肺癌。Moderna和默克计划在2024年迅速将该疗法的临床研究扩展到其他肿瘤类型。Moderna最近公布了其为期三年的2b期研究分析结果，该研究评估了INT与默沙东的抗PD-1疗法KEYTRUDA®联合治疗切除的高危黑色素瘤患者。与单独使用可瑞达相比，该组合在无复发生存率方面继续显示出改善，将复发或死亡风险降低49%，将发生远处转移或死亡的风险降低62%。其在马萨诸塞州马尔堡的新建工厂用以实现商业规模的生产罕见病疗法丙酸血症（PA）和甲基丙二酸血症（MMA）：公司预计将在2024年将其PA（mRNA-3705）和MMA（mRNA-3927）项目推进到注册研究阶段。结语展望2024年，Moderna已逐渐从新冠大流行回到研发制药公司的轨道上来。从其2024年的业务计划不难看出，Moderna将优先考虑完成多个后期管线的商业转化。值得一提的是，Moderna还加码了在中国的投资。2023年7月，Moderna公司与上海市经信委、闵行区政府在沪签署战略合作协议。同年11月，Moderna在中国首个药厂——美德纳中国研发生产总部项目在莘庄工业区开工。2023年11月28日，美德纳（上海）医药贸易有限公司拿到了营业执照，正式落户闵行。据报道，工厂运作后将首先为中国市场提供获批准的RSV疫苗。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。

mRNA-1083 showed strong immunogenicity against influenza and COVID-19, with an acceptable reactogenicity and safety profile, compared to licensed standalone vaccines Company to begin Phase 3 trial of mRNA-1083 in adults 50 years and above CAMBRIDGE, MA / ACCESSWIRE / October 4, 2023 / Moderna, Inc. (NASDAQ:MRNA) today announced positive interim results from the Phase 1/2 trial of mRNA-1083, an investigational combination vaccine against influenza and COVID-19. Moderna's investigational combination vaccines are designed to deliver value to individuals, providers and healthcare systems through higher compliance, easier administration and greater convenience. "With today's positive results from our combination vaccine against flu and COVID-19, we continue to expand our Phase 3 pipeline," said Stéphane Bancel, Chief Executive Officer of Moderna. "Flu and COVID-19 represent a significant seasonal burden for individuals, providers, healthcare systems and economies. Combination vaccines offer an important opportunity to improve consumer and provider experience, increase compliance with public health recommendations, and deliver value for healthcare systems. We are excited to move combination respiratory vaccines into Phase 3 development and look forward to partnering with public health officials to address the significant seasonal threat posed to people by these viruses." The ongoing Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT05827926) is a randomized, observer blind study evaluating the safety and immunogenicity of mRNA-1083 compared to a standard dose influenza vaccine, Fluarix, in adults 50-64 years of age and against an enhanced influenza vaccine, Fluzone HD, in adults 65-79 years of age. For both age groups, mRNA-1083 was compared against Spikevax booster. The mRNA-1083 candidate selected to advance to Phase 3 achieved hemagglutination inhibition antibody titers similar to or greater than both licensed quadrivalent influenza vaccines and achieved SARS-CoV-2 neutralizing antibody titers similar to the Spikevax bivalent booster in the Phase 1/2 study. mRNA-1083 resulted in geometric mean titer (GMT) ratios >1.0 relative to Fluarix in adults 50-64 years of age, for all four influenza vaccine strains. GMT ratios for mRNA-1083 relative to Fluzone HD in adults 65-79 were also >1.0, for all four influenza vaccine strains. The GMT ratios of mRNA-1083 relative to Spikevax bivalent were > 0.9 in adults 50 to 64 years of age and > 1.0 in adults 65 to 79 years of age, relative to Spikevax. Reported rates of solicited local and systemic adverse reactions after mRNA-1083 administration were similar to the standalone COVID-19 vaccine group in the trial. The majority of solicited adverse reactions were grade 1 or 2 in severity. Grade 3 solicited local or solicited systemic reactions were reported in less than 4% of participants ages 50 and above. No new safety concerns were identified for mRNA-1083 compared to the standalone vaccines. The Company plans to begin a Phase 3 trial of mRNA-1083 in 2023 and is targeting potential regulatory approval for the combination vaccine in 2025. Influenza epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing a substantial burden on healthcare systems. Worldwide, influenza leads to 3-5 million cases of severe diseases and 290,000-650,000 influenza-related respiratory deaths annually, despite the availability of current influenza vaccines. Influenza affects people of all ages, but older adults are disproportionately affected by influenza and its complications. The SARS-CoV-2 virus remains a leading cause of severe illness and mortality throughout the world. Since the start of the pandemic in 2020, there have been approximately 770 million cases of COVID-19 respiratory illness and approximately seven million deaths reported globally. SARS-CoV-2 infects people of all ages, but higher rates of severe illness and death are observed among older individuals and individuals with pre-existing medical conditions. The global influenza market volume is approximately 500-600 million doses annually with approximately 150 million doses administered in the United States. Moderna estimates the U.S. fall 2023 COVID-19 market size as likely to be 50 to 100 million doses, depending on vaccination rates. Over time, the Company anticipates the COVID-19 market will approach the influenza market in the U.S. given the burden of disease. The Company previously announced that it expects respiratory product sales in 2027 to be in the range of $8 billion to $15 billion with corresponding respiratory product operating profit in the range of $4 billion to $9 billion. About Moderna In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic. Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past eight years. To learn more, visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding: Moderna's development of a combination vaccine candidate against seasonal influenza and COVID-19, mRNA-1083; the potential benefits of combination vaccines; the ability of mRNA-1083 to provide protection against respiratory disease, its safety and tolerability, and protection compared to licensed comparators; the potential timeline for testing and approval of mRNA-1083; the disease burden addressed by respiratory vaccines; and the Company's anticipated future revenues from respiratory product sales and the associated operating profit from those sales. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include those other risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the year ended December 31, 2022, filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release. Moderna Contacts Media: Chris Ridley Vice President, Communications 617-800-3651 Chris.Ridley@modernatx.com Investors: Lavina Talukdar Senior Vice President & Head of Investor Relations 617-209-5834 Lavina.Talukdar@modernatx.com SpikeVax® is a registered trademark of Moderna Fluzone® is a registered trademark of Sanofi Pasteur Fluarix® is a registered trademark of the GlaxoSmithKline group of companies. SOURCE: Moderna, Inc. View source version on accesswire.com: