德国CureVac新冠mRNA疫苗失败，保护率仅47%股价近腰斩

德国研究mRNA的疫苗厂商CureVac，背景是德国政府、英国GSK和盖茨基金会，其新冠疫苗合作厂商还包括老牌药企拜耳，合作方包括英国政府，可谓豪华。

之前新冠疫苗之前进展也算顺利，入组4万人，原预计2季度就会有结果出来。同样是mRNA新冠疫苗，早期数据也还不错，大家本预期结果可以。

谁知今天晴天霹雳，2b/3期临床试HERALD研究显示该疫苗CVnCoV具有47%人群保护力。中期分析中134人感染了SARS-CoV-2，124人感染了突变株。57%的感染者感染的为较严重的VOC突变株。 

魔鬼在细节，同种路线差距同样可以很大，比如同样是重组蛋白路线，智飞与Novavax在中和抗体水平层面就相差巨大。另外，突变株影响后续等待公司分析。

CureVac新闻稿

TÜBINGEN, Germany / BOSTON, USA – June 16, 2021

CureVac N.V. (Nasdaq: CVAC), a clinical-stage biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid (“mRNA”), today announced results of the second interim analysis of its international pivotal Phase 2b/3 study in approximatively 40,000 subjects (the HERALD study) of CureVac’s first-generation COVID-19 vaccine candidate, CVnCoV. In the unprecedented context of at least 13 variants circulating within the study population subset assessed at this interim analysis, CVnCoV demonstrated an interim vaccine efficacy of 47% against COVID-19 disease of any severity and did not meet prespecified statistical success criteria. Initial analyses suggest age and strain dependent efficacy. Available data were communicated with the European Medicines Agency (EMA). The Data Safety Monitoring Board (DSMB) confirmed a favorable safety profile for CVnCoV. The study is continuing to the final analysis and the totality of the data will be assessed for the most appropriate regulatory pathway.

In total, 134 Covid-19 cases were assessed in this interim analysis. Out of these cases, 124 were sequenced to identify the variant causing the infection. The outcome confirms that only one single case was attributable to the original SARS-CoV-2 virus. More than half of the cases (57%) were caused by Variants of Concern. Most of the remaining cases were caused by other less characterised variants such as Lambda or C.37, first identified in Peru (21%) and B.1.621, first identified in Colombia (7%). In this context, the interim results suggest efficacy in younger participants but did not allow to conclude on efficacy in the age group above 60.

“While we were hoping for a stronger interim outcome, we recognize that demonstrating high efficacy in this unprecedented broad diversity of variants is challenging. As we are continuing toward the final analysis with a minimum of 80 additional cases, the overall vaccine efficacy may change,” said Dr. Franz-Werner Haas, Chief Executive Officer of CureVac. “In addition, the variant-rich environment underlines the importance of developing next-generation vaccines as new virus variants continue to emerge.”

The HERALD study, conducted by Curevac in conjunction with Bayer, enrolled approximately 40,000 participants in ten countries in Latin America and Europe. The second interim analysis included 134 cases, occurring at least two weeks after administration of the second dose. To identify strains causing COVID-19 infections within the trial, sequencing of virus variants has so far been performed on 424 COVID-19 cases, of which 124 fulfilled adjudication criteria and were included in the present efficacy analysis.

CureVac remains committed to COVID-19 vaccine development. Beyond CVnCoV, the company develops in partnership with GSK second-generation COVID-19 vaccine candidates. These candidates are based on new mRNA backbones and include potential variants in multivalent vaccine formats as well as combination vaccines for potential protection against multiple infectious diseases in one vaccine. Preclinical data from the first vaccine candidate, CV2CoV, has recently been accepted for publication in Nature Communications. CureVac and GSK expect to progress the second-generation vaccine candidate into clinical testing in the third quarter of 2021, with the goal of introducing the vaccine in 2022, subject to regulatory approval.

机翻：

CureVac(纳斯达克:CVAC)是一家临床阶段的生物制药公司，该公司开发了一类基于信使核糖核酸(“信使rna”)的新型革命性药物，今天，CureVac宣布了其国际关键性2b/3期研究(HERALD研究)的第二次中期分析结果，该研究涉及约4万名受试者，研究对象是CureVac的第一代COVID-19候选疫苗CVnCoV。在这项中期分析中评估的研究人群亚群中至少有13种变异的空前背景下，CVnCoV证明了对任何严重程度的COVID-19疾病的中期疫苗有效性为47%，且不符合预先设定的统计成功标准。初步分析表明，疗效与年龄和菌株有关。现有数据已与欧洲药品管理局(EMA)沟通。数据安全监测委员会(DSMB)证实CVnCoV具有良好的安全性。该研究将继续进行最终分析，并将对所有数据进行评估，以确定最合适的调控途径。

在中期分析中，共评估了134例Covid-19病例。在这些病例中，对124例进行了测序，以确定导致感染的变异。结果证实，只有1例病例可归因于最初的SARS-CoV-2病毒。超过一半的病例(57%)是由Concern的变异引起的。其余大多数病例是由其他特征较少的变异引起的，如Lambda或C.37(首次在秘鲁发现)和B.1.621(首次在哥伦比亚发现)(7%)。在这种情况下，中期结果表明，较年轻的参与者有效，但不允许对60岁以上的年龄组的疗效得出结论。

“虽然我们希望有一个更强的中期结果，但我们认识到，在这种前所未有的广泛的变异中展示高效是具有挑战性的。CureVac的首席执行官Franz-Werner Haas博士说:“我们正在继续进行至少80例额外病例的最终分析，疫苗的总体效力可能会改变。”“此外，随着新的病毒变异不断出现，变异丰富的环境突出了开发下一代疫苗的重要性。”

由Curevac与拜耳联合开展的《先驱报》研究招募了来自拉丁美洲和欧洲10个国家的约4万名参与者。第二次中期分析包括134例，发生在第二次注射后至少两周。为了在试验中确定导致COVID-19感染的毒株，迄今已对424例COVID-19病例进行了病毒变异的测序，其中124例符合判定标准，并被纳入目前的疗效分析。

CureVac将继续致力于COVID-19疫苗的研发。除了CVnCoV，该公司还与GSK合作开发COVID-19第二代候选疫苗。这些候选疫苗基于新的mRNA骨干，包括多价疫苗形式的潜在变体，以及一种疫苗中针对多种传染病的潜在保护组合疫苗。来自首个候选疫苗CV2CoV的临床前数据最近已被《自然通讯》杂志接受并发表。CureVac和GSK预计，第二代候选疫苗将于2021年第三季度进入临床试验，目标是在2022年推出该疫苗，有待监管部门批准。

之前5月4号接受路透采访说，由于原材料受到美国国防法案限制，难以获得，无法预估后续生产量。德国新冠疫苗厂商受限于美国出口管制，难以获得原料