Bulevirtide Acetate

连业界以高人效著称的吉利德都开始疯狂裁员，跨国药企的集体焦虑，是一天比一天重了？ 撰文| Eileen 跨国药企们近期似乎在两件事上下了大功夫：疯狂“淘金”中国创新资产；继续裁撤冗余岗位、砍管线。 当全行业的目光都被近期中国双抗的密集BD交易吸引时，跨国药企的调整消息实则也是接连不断，先是上个月两家跨国药企中国区传出裁员、砍管线，上周又有外媒报道，业内“高人效担当”吉利德及其旗下Kite公司，宣布计划裁员百人。 同期，辉瑞、BMS、赛诺菲等跨国药企的成本削减计 划，正在持续进行中。 连起来看，暗礁已经浮出水面，一个迹象愈发显著：即使研发技术不断迭代，研发费用屡屡创新高，但新药成功率几乎仍旧停滞不前。在这一急剧激化的现实矛盾下，连有钱、有资源的跨国大药企，剧烈动起来了。 去年，跨国药企在集中剥离非核心业务，将资源逐步聚焦于新兴技术创新研发，今年，跨国药企们干脆加速在更为深入的组织形态、管线布局“下狠手”，直面挑战。 40岁的Biopharma，再次“转身”了 吉利德的Biopharma成长路是经典的，但在冲击新增长点的路上，他开始显得有些无所适从。 根据外媒报道，吉利德本次裁员地主要为两个工厂，一个是位于西雅图的临床工厂，另一是吉利德旗下细胞疗法公司Kite的费城工厂。值得一提的是，费城工厂裁员只是“前菜”，2025年，这家工厂将被彻底关停。 在Kite新CEO Cindy Perettie于2023年上任初期，公司就进行过一次伴随战略调整的裁员，当时裁掉了约7%的员工。 裁员，往往都能折射出企业两面：业绩增长焦虑与战略调整方向，吉利德也并不例外。 这两次裁员就折射出吉利德的发展隐忧： 一是，曾经大张旗鼓布局的抗肿瘤管线，至今都未能反哺业绩，甚至研发接连失利，吉利德的抗肿瘤业务将走向何方？ 二是，既然抗肿瘤管线的成长期被动延长，吉利德内部的资源分配如何配合战略调整？ 这两点其实从吉利德三季度财报中也能窥得。 从业绩层面来看，今年前三季度吉利德总收入211.85亿美元，同比增长约为5.9%。其中，占总收入比将近67%的HIV业务，同比增长约5%；肝病业务和抗肿瘤业务占总收入比例相当，前者同比增长接近10%，后者同比增长约为12.87%。 不过，看似增长最快的抗肿瘤业务，却暗藏着最大的隐患。 吉利德的抗肿瘤业务在前三季度总收入24.46亿元，几乎全部来自两款CAR-T（2017年收购Kite而来）产品和一款ADC（2020年收购Immunomedics而来）。这三款产品在吉利德将其收入麾下之时，几乎都已经进入研发后期，甚至是上市阶段，可以说抗肿瘤“新手”吉利德除了花钱购买，研发上未花多大力气。这也为收购后，吉利德抗肿瘤管线研发屡屡碰壁埋下隐患。 不过，这两笔合计数百亿的巨额并购，叠加上近10年间吉利德在抗肿瘤领域进行的大大小小布局，至今都未给吉利德带来更多新的增量，没有任何新重磅产品，新适应证开发未获得质的突破。也因此，吉利德的抗肿瘤业务还在“吃老本”。 但屋漏偏逢连夜雨，增量没有，麻烦倒是有一堆。 吉利德的细胞疗法与Trop2 ADC在近几年是风波不断。先是Trop2 ADC Trodelvy在肺癌领域连连碰壁，后又在尿路上皮癌结果不尽人意。同时，Trodelvy虽然在转移性乳腺癌和三阴乳腺癌领域小有成就，但众所周知，如今来自第一三共/AZ合作的HER2 ADC DS8201正以烽火燎原之势在乳腺癌开疆拓土，来自国内药企科伦博泰也背靠默沙东成为该领域的一匹黑马。Trodelvy可以说是腹背受敌。 另外，Kite首个达到10亿美元销售额的CAR-T Yescarta也被FDA质疑可能会出现T细胞恶性肿瘤。 而在研发层面，吉利德也颇为不顺。这家MNC曾表示，到2030年底前要推出6种潜力新药，其中包括TIGIT抑制剂domvanalimab，但在该领域，罗氏和BMS都先后受阻，这让吉利德的研发蒙上了阴影。 同时，吉利德曾经49亿美元“押宝”的CD47单抗Magrolimab，已经无奈在临床III期阶段“折戟”。 想成为一家Big Pharma，似乎必须在兵家必争之地——肿瘤领域占据一席之地，但很明显，吉利德在这一领域花了高价，但吃了大亏。 反倒是在传统强势的HIV和肝病上，吉利德仍然稳居全球最强梯队，甚至好消息频传。 例如，重磅预防HIV新药Lenacapavir作为上述吉利德未来的6款“潜力股”新药之一，不仅达到了每半年注射一次的给药频率，其用于预防HIV感染的关键III期试验PURPOSE 2还取得了“高达99.9%未感染艾滋病毒”的效果。该产品的全球上市申请也已经提上日程。Lenacapavir也有潜力接棒Biktarvy，成为吉利德另一HIV超级重磅炸弹。 吉利德的另一款HDV产品Hepcludex，不仅是一款First-in-class潜力股，其在近期发布2b期临床数据显示，也存在长期抑制HDV病毒的潜力。 也就是说，辗转多年，曾经受全世界创业科学家追捧的吉利德，扛起未来增长重任的或许还是“一战成名”的HIV产品，以及助力其走向更大规模的肝病产品。而吉利德要想进入全球抗肿瘤第一梯级，仍需“修炼”。 另一方面，虽然从收入和业务布局两个层面来看，吉利德的确算是已经步入Bigpharma阶段，但其企业管理风格和研发模式，相较于辉瑞、BMS等跨国大药企，其实与Biopharma仍然十分接近。 这点从人均创收上就能明显看出。如果粗略计算人均创收，吉利德和辉瑞截至2023年年底的员工总数分别约为18000人和88000人，按照二者的全年收入271.16亿美元和585亿美元计算，吉利德的人均创收约为150万美元，而辉瑞约为60万美元。 而2023年总收入98.7亿美元，员工总数5400人的福泰，人均创收也不过约183万美元。 也就是说，现如今人效接近Biopharma水平的吉利德都在裁员，似乎在暗示出不管是辉瑞、BMS等超大型跨国药企，还是吉利德这种人效更高的中型跨国药企，似乎都在进行战略调整，更进一步的是，他们似乎都在将资源向传统优势领域倾斜。 MNC集体“回归” 一般来讲，制药企业的三季报几乎已经可以反映出全年的业绩水平，而从这一角度看全球营收TOP10的跨国药企的2024前三季度营收，他们都在面临不同程度的增长乏力困境。 而面对这些困境，裁员与回归，贯穿在了这些跨国药企的调整动作之中。 例如辉瑞，2023年将Seagen收入麾下的同时，也成立了“the Pfizer Oncology Division”（辉瑞肿瘤事业部），并且之后又实施了高达40亿美元的“成本调整计划”和“销售成本削减计划”，以及接连裁员百人。 不过，辉瑞调整的结果从其三季度财报来看，似乎颇有成效。一方面，其第三季度总收入177.02亿美元，同比增长32%，除去新冠产品影响，增长率能达到14%。另一方面，Seagen带来的几款ADC产品，似乎也成了辉瑞在哌柏西利收入下滑后，增长的新动力，包括Nectin-4 ADC Padcev、CD30 ADC Adcetris、HER2 ADC Tukysa、TF ADC Tivdak合计在第三季度收入8.54亿美元。辉瑞肿瘤整体增长率达31%。 同样裁员与战略调整双至的跨国药企还有赛诺菲。去年10月，赛诺菲宣布其“Play to Win”开启新篇章，增加研发投入，更加聚焦免疫新产品的研发。随之而来就是赛诺菲为提升研发效率，简化架构所进行的关停管线和裁员，节约7亿欧元的成本。 值得一提的是，在开启新篇章的同时，赛诺菲也再次释放出在自免领域称王称霸的雄心壮志——在未来短短两年内将III期临床试验的数量增加50%。 除了上述两项调整外，赛诺菲的消费者健康业务也有望赶上这一波跨国药企剥离的风潮。一个月前就有外媒报道，赛诺菲有意出售消费者健康业务50%股权。 当然，在赛诺菲的一系列调整下，度普利尤单抗几乎排到了全球畅销药阵营中增速最快的梯级，今年前三季度收入96.14亿欧元，同比增长率也高达25.9%（CER）。 强生的裁员颇受业界关注。不仅在2023年，强生全球随着关闭心血管和代谢部门、裁撤美国工厂员工而降临的多次裁员，前不久，其中国区甚至也流传出外科产品线裁员的消息。 但强生的裁员，以及在几年前剥离科赴，如今似乎并未减缓“青黄不接”风险的降临。 在强生收入最高的自免领域，三款核心产品英夫利昔单抗、古赛奇尤单抗、乌司奴单抗都正在遭遇挑战。2023年，强生自免板块业务占比有所下滑，英夫利昔单抗销售额降幅尤其严重；古赛奇尤单抗身处于IL-23抑制剂这一天花板自免赛道，但作为全球首款IL-23单抗药物，其在2023年增速放缓；乌司奴单抗终于突破百亿美元门槛，但其在美国的主要专利正式在2023年到期。 而到了2024年三季度，强生的自免业务前九个月总营收达135.9亿美元，增长却仅为1%。 事实上，在全球头部的跨国药企中，今年以来裁员的不在少数，除了上述企业，罗氏、BMS、GSK等都宣布了不同程度的裁员计划，涉及范围也在研发到生产等不同环节。 而这些调整的背后，其实是跨国药企集体对于研发效率的焦虑。德勤在一份报告中指出，TOP20的MNC公司研发效率几年来一直在持续下降，研发一项新药的平均成本已经超过20亿美元，而回报率却低至1.2%。 不过，这些MNC其实都在遵循一个共同的逻辑，抛弃或是减少过往在多元化业务上的资源投入，重新回归传统强势的领域。例如肿瘤之于辉瑞、自免之于强生，呼吸、抗感染之于GSK。而他们的底层逻辑也不难理解，在研发技术持续进步，研发投入年年水涨船高，成功率却止步不前的当下困境中，只有“开源节流”，才能获得新的增长，将有限资源投入到已经形成优势的领域，进一步深耕。 一审| 黄佳 二审| 李芳晨 三审| 李静芝 精彩推荐 CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化 ｜ 猎药人系列专题 | 出海 启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册 创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖 ｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 |  荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药 ｜再鼎医药｜亚虹医药 跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

– Monthly tobevibart and elebsiran combination achieves rapid 100% virologic suppression at Week 24, sustained through Week 60 – – Undetectable HDV RNA in 41% of participants at Week 24, increasing to 64% by Week 36 and up to 80% by Week 60 across cohorts – – Combination well-tolerated: no treatment-related severe AEs, treatment-related discontinuations or ALT flares – – Following a recent FDA meeting, Phase 3 ECLIPSE registrational program to begin in the first half of 2025 – – New data presented at AASLD The Liver Meeting. Investor conference call November 19, 2024, at 5.15 a.m. PT / 8.15 a.m. ET – SAN FRANCISCO, CA, USA I November 18, 2024 I Vir Biotechnology, Inc. (NASDAQ:VIR) today announced positive results from the SOLSTICE Phase 2 clinical trial evaluating tobevibart alone, or in combination with elebsiran, in people with chronic hepatitis delta (CHD). The most-advanced and potential first-of-its-kind investigational human monoclonal antibody and siRNA combination dosed monthly achieved 100% virologic response and rapid hepatitis delta virus (HDV) RNA suppression. HDV RNA below the lower limit of quantification (< LLOQ), target not detected (TND), the best measure that the virus is cleared from the body, was achieved in 41% (13/32) of participants at Week 24 rising to 64% (14/22) of participants by Week 36. In a cohort that reached Week 60, 80% (4/5) achieved HDV RNA TND. These data were presented in an oral session at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting ® , in San Diego, CA. Based on these results, and following a recent meeting with the FDA, Vir Biotechnology plans to initiate the Phase 3 registrational ECLIPSE program in the first half of 2025 to further evaluate the combination of tobevibart and elebsiran for the treatment of CHD. CHD is a chronic inflammatory liver disease caused by HDV 1 . It is the most severe form of chronic viral hepatitis 2 and on average, people living with CHD will progress to cirrhosis and liver failure within 5 years 3 . There is no approved treatment in the United States. The objective of therapy is to clear the virus, and combination therapy offers the potential to do so by tackling the viral lifecycle through multiple mechanisms. “Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta. The impressive rates of virologic suppression seen in the SOLSTICE Phase 2 data suggest that tobevibart and elebsiran have the potential to significantly improve patient outcomes,” said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité, and Head of the unit Viral Hepatitis UMR1149 at INSERM, France. “New, effective therapeutic options are urgently needed, and I am excited to see this combination advance into a registrational Phase 3 program.” Primary Endpoint Analysis from the Phase 2 SOLSTICE Trial Clinical trial participants were randomized to receive tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination de novo arm, n=32). In addition, the participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover, n=13). Rates of virologic suppression were evaluated at Week 24, and further assessed at Weeks 36, 48 and 60 in those participants that had reached each timepoint. Further monitoring will continue up to 192 weeks. Rapid and Sustained Virologic Suppression – 100% of participants across combination arms achieved an HDV RNA ≥2 log 10 decrease or below limit of detection (LOD) at Week 24, and this rate was sustained over time in all participants at Weeks 36 (22/22) and those in the rollover cohort that reached Week 60 (5/5). HDV RNA TND was achieved in 41% (13/32) of participants across combination arms at Week 24 and this rose to 64% (14/22) at Week 36. By week 60, this had risen further with 80% (4/5) of participants in the rollover cohort having achieved no detectable viral RNA. Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24, with sustained responses at later time points. This indicates suppression of the key biologic mechanisms that HDV requires for viral replication. ALT Normalization – Alanine aminotransferase (ALT) decreased in most participants between Day 1 and Week 24 and normalized in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the rollover cohort by Week 24. These rates were sustained at Week 36. Combined Endpoints – The protocol defined combined endpoint of HDV RNA decrease ≥ 2 log 10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% (15/32) of participants in the combination de novo arm. The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, which increased to 27% (6/22) by Week 36. This trend was reflected in the combination rollover cohort in which 33% (3/9) of participants achieved this endpoint at Week 24 and 40% (2/5) at Week 60. Rates of HDV RNA suppression and ALT normalization were similar between non-cirrhotic and cirrhotic participants across combination arms. Safety Profile – The safety profile of tobevibart and elebsiran is consistent with previous studies. Treatment-emergent adverse events (TEAEs) were generally mild or moderate and transient across all treatment groups, with influenza-like illness being the most common event. No ALT flares were observed. There were no study-related discontinuations in the combination arms, and no treatment-related severe adverse events (SAEs) were reported. “People living with hepatitis delta in the US have no approved treatment options, and therapies are limited globally. At Vir Biotechnology we are committed to changing that,” said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. “We are confident that our regimen has the potential to deliver transformative benefits for patients, and we will build on our strong SOLSTICE data to start our Phase 3 registrational ECLIPSE program as soon as possible in 2025.” Phase 3 Registrational ECLIPSE Program Following a meeting with the FDA, Vir Biotechnology finalized the design of the Phase 3 registrational clinical program, ECLIPSE, which evaluates the tobevibart and elebsiran combination in people living with CHD. This program, which will commence in the first half of 2025, will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide. All studies will enroll both cirrhotic and non-cirrhotic participants. ECLIPSE 1 and 2 are Phase 3 trials designed to provide the registrational efficacy and safety data needed for submission to global regulatory agencies. ECLIPSE 3 is a Phase 2b trial designed to provide important supportive data, particularly in Europe, to help establish appropriate pricing and reimbursement in key markets. In June 2024, the U.S. Food and Drug Administration (FDA) granted fast track designation for the combination of tobevibart and elebsiran for the treatment of CHD. This designation is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Vir Biotechnology announced today that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on the application for orphan drug designation of tobevibart and elebsiran for the treatment of CHD. This designation supports the development of treatments for life-threatening or chronically debilitating conditions with significant unmet medical need. Investor Conference Call Vir Biotechnology will host an investor conference call on November 19, 2024 at 5.15 a.m. PT / 8.15 a.m. ET. A live webcast will be available on https://investors.vir.bio/ and will be archived on www.vir.bio for 30 days. About the Phase 2 SOLSTICE Trial SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in people with chronic hepatitis delta. This Phase 2 study is a multi-center, open-label, randomized study. Primary endpoints include proportion of participants with undetectable hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or greater than 2 log 10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks. Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints and up to 192 weeks. More information about this trial can be found at clinicaltrials.gov (NCT05461170). About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies. Tobevibart and elebsiran are also being evaluated as a potential functional cure for chronic hepatitis B. Vir Biotechnology recently presented positive safety and efficacy end-of-treatment results from the MARCH Phase 2 clinical study evaluating combinations of tobevibart and elebsiran, alone or in combination with pegylated interferon alfa (PEG-IFNα), in participants with chronic hepatitis B in a late-breaker oral presentation at AASLD The Liver Meeting ® . About Vir Biotechnology, Inc. Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. It’s clinical-stage portfolio includes infectious disease programs for chronic hepatitis delta and chronic hepatitis B infections and programs across several clinically validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of other infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis D – NIDDK (nih.gov) , accessed September 2024 2 WHO Hepatitis Delta Factsheet – Hepatitis D (who.int) , accessed September 2024 3 CDC What is Hepatitis D – FAQ | CDC SOURCE: Vir Biotechnology