去年春天,新冠疫情蔓延初现苗头之时,辉瑞公司的科学家就开始了疫苗的研发,用首席执行官艾伯乐的话来说就是“让不可能变成可能”。
如今,在实现以惊人速度成功开发出世界上第一款新冠疫苗目标后,成立172年的制药商领导者向我们谈起了科学与政治的冲突、药价,还有下一项不可能完成的任务。
为表述简洁,本文已经过编辑。
全心关注科学
2020年3月初,在你担任辉瑞公司首席执行官刚满一年的时候,几乎第一时间决定投入20亿美元资金研发新冠疫苗。是什么驱使你下这么大赌注?
艾伯乐:确实是巨大的赌注,但非常有必要。在疫苗研发领域,像辉瑞一样拥有端到端能力的公司并不多,只有辉瑞级别的公司才能从早期研究开始,一路坚持,不仅能制造,还能承担挑战巨大的分销工作。
所以我想到的问题是,“如果我们不做,还能找谁?”
生产疫苗有很多已被证实的方法,你选择了以前从未生产过获批疫苗的mRNA技术。这是为什么?
我知道辉瑞(与德国BioNTech公司合作)正在研究防治流感的mRNA疫苗,有继续防治其他疾病的腺病毒疫苗,之前还有重组蛋白。
但我的团队(由疫苗研究负责人凯瑟琳•简森领导)仔细研究了每项技术,建议选择mRNA,因为一旦研发成功,mRNA可迅速扩大规模。的确,以前没用mRNA技术制造过疫苗,但如果我们成功了,就会成为第一个。
我的团队想尽快开始。BioNTech(首席执行官是乌古尔•萨欣,3月1日一次电话中跟简森联系)也表示,希望尽快完成研发工作。所以我们开始投资,他们在没签合同的情况下就开始跟我们共享数据。
你的日常工作是寻找解决方案,持续推动辉瑞增长。你预计年收入增长率很快将达到6%,这远高于过去几年的水平。现在对这一预期还有信心吗?
现在我很有信心。而且我想说,预计收入增长“至少6%”。6%不是天花板,而是起步水平。我非常有信心,排除新冠疫苗的带动作用,其他业务部门也能达到该数字。
除此之外,我们也要加强疫苗在财务方面的带动效果。目前还没有公布预测,但我相信收入会超过30亿美元。
实现快速供应是选择mRNA疫苗的原因之一。另一个好处是,可以迅速调整疫苗的基因配方,而且随着病毒不断变异出现更多变种,可能很有必要。
没错,速度和灵活性是关键。这正是我们选择采用该技术生产流感疫苗的原因。流感也有同样特征,每年的流感都不一样。所以每年的流感疫苗也都跟前一年不同。(如果使用其他技术)每一步都需要几个月开发。RNA疫苗可能突破该限制,数周内就能完成其他情况下数月才能完成的任务。
当前新冠病毒变异引起警觉。辉瑞公司的疫苗对变异毒株的效果怎样?
我们对抵抗变异病毒的信心很强。我们在实验室里已证明了这一点,而且实验室的实验已在大学和医院多个实验室中成功得到复制。目前疫苗能有效预防见诸报端的两种新变异病毒(在英国和南非出现)。
我认为最根本的问题是,疫苗无法覆盖的新变异出现可能性有多大?理论上可能性很高。如果疫苗保护了相当大一部分人群,却出现一种可在(已接种疫苗)群体传播的菌株,显然新菌株将取代原有菌株蔓延。有不确定性,但我相信存在可能。即便如此也能证明mRNA疫苗的作用,因为可以很快开发新疫苗,既可以提升免疫原性,也能开发出全新疫苗应对新变异。
“快”有多快?
取决于多种因素,监管框架就是其中之一。我相信两个月内能通过,当然我们仍有可能在风险下生产。
说到风险,你还下了第二个大赌注,跟一些你们的竞争对手不同,你们研发疫苗没有用政府的钱。
政府说,“我们可以为项目提供资金。”但听到提议时,我想了想如果接受资金会发生什么,其实很容易判断。我意识到,如果政府给钱就不可能不掌控。“你们打算怎么做?”他们会这么问,“钱怎么用?给我们提交报告。”
在辉瑞这样的大公司里,本来就要面临很多官僚层级。我敢说自己能掌控一切,作为公司最终决策者,我会放弃一切官僚作风。我的目标是,“直接跟我说,我要替换所有管理部门。”
但如果我拿政府的钱就做不到。我很清楚,如果不大刀阔斧就永远无法把不可能变成可能。举个例子,请记住我们起步要比Moderna晚得多。当然我们也不需要政府的钱。Moderna肯定需要。如果我们失败了日子会难过吗?当然。但如果我们失败了辉瑞会迎来末日吗?绝对不会。
这就是为什么我能这么做,正确地承担风险,不鲁莽但也不保守,世界需要我们时,坚持不动摇。
尽管你很好地部署了所有物流工作,但人们还是普遍对疫苗推广感到失望。出了什么问题?
物流有两个阶段。有一个阶段我非常担心,辉瑞公司正把疫苗送到各国疫苗接种中心。这是我们的责任,幸运的是,我们能成功完成这一困难的任务。几乎99.99%的疫苗都能在确保质量的情况下按时成功送达,因为我们能监控所有物流箱的温度。
但包括美国在内很多国家还没准备好分发相关疫苗,他们的的疫苗接种中心能力不足。我相信也希望这些国家能团结起来,改变计划,从而大幅提高疫苗接种率。
如果各国能做到,我们可能经历一段时间的瓶颈期,需要生产更多疫苗,我们正为此做准备。最近公司宣布,今年预期产量将从13亿剂增加到20亿剂。
一切都是政治
尽管制造和分发新型疫苗的任务非常复杂,过去一年里你不得不面对更具挑战性的事:政治。尤其是你暗示疫苗可能于去年10月上市时,发现自己处于复杂的总统竞选斗争中心。
这是一场完全不同的比赛,跟我预期中完全不同。请让我澄清一下。10月面世的时间表是我跟团队在3月就已制定好的,当时我还催着团队尽可能快地前进。
我当时觉得10月是流感季节,却没想到,11月正好碰上大选。突然间,疫苗成了最大的政治问题。我听到第一次总统辩论时,非常震惊的是,讨论新冠病毒和疫苗时充满政治词汇而不是科学术语。
第二天我发表声明说,有些人希望我们进度加快,有些人希望我们慢一点。要我说就是,以科学的速度推进。就这样。
然后,疫苗在11月大选之后面世。现在,有些人认为“太早”,有些人认为“太迟”。我们能怎么办?我努力在政治雷区中航行。
当初没拿政府的钱原因之一就是,如果我们用了政府的钱,做的每件事都会更政治化。
你曾打电话给强生公司首席执行官亚历克斯•戈尔斯基,讨论同制药行业的其他领导者团结起来,反击疫苗工作政治化。为什么这样做,结果如何?
就在那时,有些人公开指责美国食品药品管理局是“国家黑势力”,我开始非常担心,因为有望成功的疫苗被政治化已然开始。
人们面对现状会有很多困惑和疑虑,不禁要问:这是特朗普疫苗,还是真正的疫苗——真正科学的那种?唯一能担任仲裁和法官的,是以科学正直闻名的食品药品管理局。这些无疑是值得信任的机构。所以我担心对食品药品管理局的攻击,也是对疫苗工作独立性和科学完整性的攻击。
亚历克斯•戈尔斯基是我的好朋友,我们经常讨论很多事,所以我问了他。我说,我认为需要做些什么,要发表声明,宣称无论发生什么,永远不会偷工减料,不管别人施加多大压力,政治压力也好,其他压力也好,都将遵循食品药品管理局指导方针。
他立刻说:“你说得对,这就是我们应该做的事。”我说,“要不写点什么?”第二天我给他发了一份声明草稿,他看了之后发了回来。我说,“每个人都得签字。”
于是我们列出了(业内)公司的名单,并各自拿了一半名单,开始打电话。大家都是立刻接受了。
白宫换了新一届政府,也有了新国会。这听起来是推动药品定价长期解决方案的好机会,也是持续困扰行业的问题。
我首先要说,我坚信改革的必要性。目前的现状不可持续也不可取,我身边绝大多数同行也都支持这一观点。每个人都说需要改变,但我认为变革必须有两个基本支柱,一是支持创新,二是保持耐心。
美国在药品定价问题上有一场大辩论。但药品价格涉及两个方面:一是系统中药品的成本,例如联邦预算中的医疗保险。第二个问题是,对于去药店必须自掏腰包的人来说,药品的成本是多少?
两点很不一样。第一个数字(医疗系统支付的药品费用)占医疗总体费用的12%。所以从定义上讲,这不可能是个“大”问题?
对于病人来说,尤其是自付医药费的病人来说,这是迄今为止要面临的最大挑战。因为现在美国人即便有医保,为药品买单时也仿佛没有医保一样,人们自付金额非常多。这种情况需要改变。
要把费用从病人手中转移出去,就得有人付钱,因为这并不是零和的。我们愿意承担病人自付费用里很大一部分。我的意思并不是,也认为没人会说医药公司赚走所有的钱是公平的。但我们愿意只取应得的一份,甚至更多。这是钱的合理流向。
我认为这笔钱不应该用来填补联邦预算的黑洞,因为预算漏洞会越来越大。无论如何,我们必须找到解决办法,要尽快,今年就得找到。
你认为新冠疫情对社会的挑战会持续多久?对辉瑞的业务意味着什么?
这没法确定,而且就目前而言,如果涉及投资者就要把疫苗当做单独的项目。因此,我们将让投资者了解基本业务,以及疫情相关业务的贡献、最高和最低情况。因为这可能是一次性的,或者是两年、三年之类。事实上从很多指标来看,这项业务可能永远持续下去,就像流感一样,就像肺炎球菌病一样。这不仅因为人们可能需要定期(打加强针)应对当前的毒株,还因为可能出现新的变异病毒,届时就像应对流感一样改进疫苗。
我不知道未来会不会是这样,我只知道,我们正在为相关情况做准备。所以说,公司正努力加强长期实力,确保完善流程。如果出现变异病毒也能迅速应对(我之前说过,六周或两个月内就可以)。我们也在制造更适合运输的疫苗,避免冷链出现问题。虽然研发很成功,但问题仍旧很复杂,成本也很昂贵。
顺便说一句,辉瑞承担了运送疫苗的所有费用。如果我们能找到更好的解决办法,对于达到业务最低目标将大大有利。
谈谈流感吧。几十年来,人们一直在急切地寻找“通用疫苗”,就是能应对每个季节出现的各种流感病毒的疫苗。在新冠危机之前,辉瑞公司就在跟BioNTech合作开发mRNA流感疫苗。能给出具体时间表吗?
我希望比之前计划快得多。因为现在已经证明我们能让不可能成为可能。另外,过去九个月里,我们积累了RNA技术方面的科学知识,正常情况下积累相关知识需要很多年。
现在我不想承诺流感疫苗研发的具体日期,但计划是以比平时快得多的速度(推向市场)。现在很多情况下,流感疫苗有效性只有40%或50%,我们的目标是研制对流感有效性超过90%的疫苗。届时将影响整个行业,我们希望能尽快做到。
考虑到癌症是遗传性疾病,mRNA平台会不会在个体化、靶向癌症药物中发挥作用?想必,快速研制个体化靶向药物的原则也可应用。
完全没问题。事实上,BioNTech大部分工作都在癌症领域,我相信mRNA技术可为癌症治疗开辟很多新途径。
你的职业生涯是从兽医开始的,现在大部分时间都花在人类疾病上。研究动物健康是不是能帮你看到其他人可能忽视的事?
我相信每一点不同寻常都能带来不同的视角。正如你提到,我是兽医,所以我了解科学,从而能够更好地与药物研发团队沟通。我还曾在辉瑞动物健康部门工作(后来分拆成Zoetis公司),11年前我转到人类健康部门时,我发现当时的制药巨头非常注重品牌,确实品牌非常重要。而在动物卫生领域不会这样,兽医行业重要的是顾客——是主人和狗。
我的出身也给了我一些特别的视角,由于我来自希腊这样有着辉煌历史,现实中在国际谈判桌上重要性却不大的小国家,你要学会如何去战斗,过程其实并不容易。
大屠杀期间希腊犹太人几乎灭绝,我身为犹太人也学会了适应,在社会上要懂得灵活应对才能生存。我母亲被捕后活了下来,父亲躲起来也成了幸存者。他们的家人命运却不一样,兄弟和父母都被杀死了。
我在辉瑞工作期间,曾在五个国家的八个城市生活,从中也体会到了多样性的力量,也感受到每种文化都是独一无二的,从而能贡献一些价值。由于我的自身经历,因而对此非常敏感。所有种种都帮我形成自己独有的视角,我认为所有经历都是有帮助的。
补充信息
(1)收到的信息:传统疫苗使用失去部分活性,或完全失去活性的病毒激活免疫反应,而利用信使RNA的疫苗不一样,主要通过指示细胞制造与病毒相关的无害蛋白质,从而向免疫防御系统发出警报。
(2)连续五年年收入增长:公司指出,虽然辉瑞的生物制药业务强劲增长,然而之前Upjohn部门(最近先被迈兰制药剥离又合并)收入下降,2019年与葛兰素史克成立了消费医疗合资企业,增长都被抵消。
百时美施贵宝:19.0%
艾伯维:13.2%
默沙东:3.6%
强生:3.3%
礼来:3.3%
阿斯利康:0.7%
辉瑞:0.3%
(来源:标普环球)
(3)梦之队:疫情之前,辉瑞和BioNTech正合作研发流感疫苗。“现在很多情况下,流感疫苗有效性不到50%,”艾伯乐说。随着新冠疫苗研制成功,他预计两家合作伙伴“将成功研发出有效性最终超过90%的流感疫苗。”
(4)推动的赞助者:几家美国机构资助了规模比辉瑞小得多的Moderna公司,协助基于mRNA的新冠疫苗研发工作。Moderna疫苗获得食品药品管理局紧急使用授权比辉瑞疫苗晚了一周。
(5)从实验室到物流:辉瑞已向全球10000多个接种点,提供了超过5000万剂疫苗。
(6)仪表盘灯光下:数字并非是估计值。辉瑞通过实时仪表盘跟踪运送疫苗的实际成功率,仪表盘通过全球定位系统监控每个疫苗物流箱的位置和温度。
(7)动物精神:艾伯乐拥有执业兽医和博士学位,曾在希腊一所大学医院从事兽医产科工作5年,专长体外受精、人工受精和胚胎移植等。
(8)希腊悲剧:艾伯乐说,“在我家乡萨洛尼卡曾经有55000犹太人,大屠杀中幸存者只有2000人。后来很多人离开了。等我长大后,我们社区大概700到800人,但占了全城犹太人口的一半。”(财富中文网)
本文刊载于《财富》杂志2021年2月/3月刊,标题是《对话:艾伯乐》。
译者:冯丰
审校:夏林
去年春天,新冠疫情蔓延初现苗头之时,辉瑞公司的科学家就开始了疫苗的研发,用首席执行官艾伯乐的话来说就是“让不可能变成可能”。
如今,在实现以惊人速度成功开发出世界上第一款新冠疫苗目标后,成立172年的制药商领导者向我们谈起了科学与政治的冲突、药价,还有下一项不可能完成的任务。
为表述简洁,本文已经过编辑。
全心关注科学
2020年3月初,在你担任辉瑞公司首席执行官刚满一年的时候,几乎第一时间决定投入20亿美元资金研发新冠疫苗。是什么驱使你下这么大赌注?
艾伯乐:确实是巨大的赌注,但非常有必要。在疫苗研发领域,像辉瑞一样拥有端到端能力的公司并不多,只有辉瑞级别的公司才能从早期研究开始,一路坚持,不仅能制造,还能承担挑战巨大的分销工作。
所以我想到的问题是,“如果我们不做,还能找谁?”
生产疫苗有很多已被证实的方法,你选择了以前从未生产过获批疫苗的mRNA技术。这是为什么?
我知道辉瑞(与德国BioNTech公司合作)正在研究防治流感的mRNA疫苗,有继续防治其他疾病的腺病毒疫苗,之前还有重组蛋白。
但我的团队(由疫苗研究负责人凯瑟琳•简森领导)仔细研究了每项技术,建议选择mRNA,因为一旦研发成功,mRNA可迅速扩大规模。的确,以前没用mRNA技术制造过疫苗,但如果我们成功了,就会成为第一个。
我的团队想尽快开始。BioNTech(首席执行官是乌古尔•萨欣,3月1日一次电话中跟简森联系)也表示,希望尽快完成研发工作。所以我们开始投资,他们在没签合同的情况下就开始跟我们共享数据。
你的日常工作是寻找解决方案,持续推动辉瑞增长。你预计年收入增长率很快将达到6%,这远高于过去几年的水平。现在对这一预期还有信心吗?
现在我很有信心。而且我想说,预计收入增长“至少6%”。6%不是天花板,而是起步水平。我非常有信心,排除新冠疫苗的带动作用,其他业务部门也能达到该数字。
除此之外,我们也要加强疫苗在财务方面的带动效果。目前还没有公布预测,但我相信收入会超过30亿美元。
实现快速供应是选择mRNA疫苗的原因之一。另一个好处是,可以迅速调整疫苗的基因配方,而且随着病毒不断变异出现更多变种,可能很有必要。
没错,速度和灵活性是关键。这正是我们选择采用该技术生产流感疫苗的原因。流感也有同样特征,每年的流感都不一样。所以每年的流感疫苗也都跟前一年不同。(如果使用其他技术)每一步都需要几个月开发。RNA疫苗可能突破该限制,数周内就能完成其他情况下数月才能完成的任务。
当前新冠病毒变异引起警觉。辉瑞公司的疫苗对变异毒株的效果怎样?
我们对抵抗变异病毒的信心很强。我们在实验室里已证明了这一点,而且实验室的实验已在大学和医院多个实验室中成功得到复制。目前疫苗能有效预防见诸报端的两种新变异病毒(在英国和南非出现)。
我认为最根本的问题是,疫苗无法覆盖的新变异出现可能性有多大?理论上可能性很高。如果疫苗保护了相当大一部分人群,却出现一种可在(已接种疫苗)群体传播的菌株,显然新菌株将取代原有菌株蔓延。有不确定性,但我相信存在可能。即便如此也能证明mRNA疫苗的作用,因为可以很快开发新疫苗,既可以提升免疫原性,也能开发出全新疫苗应对新变异。
“快”有多快?
取决于多种因素,监管框架就是其中之一。我相信两个月内能通过,当然我们仍有可能在风险下生产。
说到风险,你还下了第二个大赌注,跟一些你们的竞争对手不同,你们研发疫苗没有用政府的钱。
政府说,“我们可以为项目提供资金。”但听到提议时,我想了想如果接受资金会发生什么,其实很容易判断。我意识到,如果政府给钱就不可能不掌控。“你们打算怎么做?”他们会这么问,“钱怎么用?给我们提交报告。”
在辉瑞这样的大公司里,本来就要面临很多官僚层级。我敢说自己能掌控一切,作为公司最终决策者,我会放弃一切官僚作风。我的目标是,“直接跟我说,我要替换所有管理部门。”
但如果我拿政府的钱就做不到。我很清楚,如果不大刀阔斧就永远无法把不可能变成可能。举个例子,请记住我们起步要比Moderna晚得多。当然我们也不需要政府的钱。Moderna肯定需要。如果我们失败了日子会难过吗?当然。但如果我们失败了辉瑞会迎来末日吗?绝对不会。
这就是为什么我能这么做,正确地承担风险,不鲁莽但也不保守,世界需要我们时,坚持不动摇。
尽管你很好地部署了所有物流工作,但人们还是普遍对疫苗推广感到失望。出了什么问题?
物流有两个阶段。有一个阶段我非常担心,辉瑞公司正把疫苗送到各国疫苗接种中心。这是我们的责任,幸运的是,我们能成功完成这一困难的任务。几乎99.99%的疫苗都能在确保质量的情况下按时成功送达,因为我们能监控所有物流箱的温度。
但包括美国在内很多国家还没准备好分发相关疫苗,他们的的疫苗接种中心能力不足。我相信也希望这些国家能团结起来,改变计划,从而大幅提高疫苗接种率。
如果各国能做到,我们可能经历一段时间的瓶颈期,需要生产更多疫苗,我们正为此做准备。最近公司宣布,今年预期产量将从13亿剂增加到20亿剂。
一切都是政治
尽管制造和分发新型疫苗的任务非常复杂,过去一年里你不得不面对更具挑战性的事:政治。尤其是你暗示疫苗可能于去年10月上市时,发现自己处于复杂的总统竞选斗争中心。
这是一场完全不同的比赛,跟我预期中完全不同。请让我澄清一下。10月面世的时间表是我跟团队在3月就已制定好的,当时我还催着团队尽可能快地前进。
我当时觉得10月是流感季节,却没想到,11月正好碰上大选。突然间,疫苗成了最大的政治问题。我听到第一次总统辩论时,非常震惊的是,讨论新冠病毒和疫苗时充满政治词汇而不是科学术语。
第二天我发表声明说,有些人希望我们进度加快,有些人希望我们慢一点。要我说就是,以科学的速度推进。就这样。
然后,疫苗在11月大选之后面世。现在,有些人认为“太早”,有些人认为“太迟”。我们能怎么办?我努力在政治雷区中航行。
当初没拿政府的钱原因之一就是,如果我们用了政府的钱,做的每件事都会更政治化。
你曾打电话给强生公司首席执行官亚历克斯•戈尔斯基,讨论同制药行业的其他领导者团结起来,反击疫苗工作政治化。为什么这样做,结果如何?
就在那时,有些人公开指责美国食品药品管理局是“国家黑势力”,我开始非常担心,因为有望成功的疫苗被政治化已然开始。
人们面对现状会有很多困惑和疑虑,不禁要问:这是特朗普疫苗,还是真正的疫苗——真正科学的那种?唯一能担任仲裁和法官的,是以科学正直闻名的食品药品管理局。这些无疑是值得信任的机构。所以我担心对食品药品管理局的攻击,也是对疫苗工作独立性和科学完整性的攻击。
亚历克斯•戈尔斯基是我的好朋友,我们经常讨论很多事,所以我问了他。我说,我认为需要做些什么,要发表声明,宣称无论发生什么,永远不会偷工减料,不管别人施加多大压力,政治压力也好,其他压力也好,都将遵循食品药品管理局指导方针。
他立刻说:“你说得对,这就是我们应该做的事。”我说,“要不写点什么?”第二天我给他发了一份声明草稿,他看了之后发了回来。我说,“每个人都得签字。”
于是我们列出了(业内)公司的名单,并各自拿了一半名单,开始打电话。大家都是立刻接受了。
白宫换了新一届政府,也有了新国会。这听起来是推动药品定价长期解决方案的好机会,也是持续困扰行业的问题。
我首先要说,我坚信改革的必要性。目前的现状不可持续也不可取,我身边绝大多数同行也都支持这一观点。每个人都说需要改变,但我认为变革必须有两个基本支柱,一是支持创新,二是保持耐心。
美国在药品定价问题上有一场大辩论。但药品价格涉及两个方面:一是系统中药品的成本,例如联邦预算中的医疗保险。第二个问题是,对于去药店必须自掏腰包的人来说,药品的成本是多少?
两点很不一样。第一个数字(医疗系统支付的药品费用)占医疗总体费用的12%。所以从定义上讲,这不可能是个“大”问题?
对于病人来说,尤其是自付医药费的病人来说,这是迄今为止要面临的最大挑战。因为现在美国人即便有医保,为药品买单时也仿佛没有医保一样,人们自付金额非常多。这种情况需要改变。
要把费用从病人手中转移出去,就得有人付钱,因为这并不是零和的。我们愿意承担病人自付费用里很大一部分。我的意思并不是,也认为没人会说医药公司赚走所有的钱是公平的。但我们愿意只取应得的一份,甚至更多。这是钱的合理流向。
我认为这笔钱不应该用来填补联邦预算的黑洞,因为预算漏洞会越来越大。无论如何,我们必须找到解决办法,要尽快,今年就得找到。
你认为新冠疫情对社会的挑战会持续多久?对辉瑞的业务意味着什么?
这没法确定,而且就目前而言,如果涉及投资者就要把疫苗当做单独的项目。因此,我们将让投资者了解基本业务,以及疫情相关业务的贡献、最高和最低情况。因为这可能是一次性的,或者是两年、三年之类。事实上从很多指标来看,这项业务可能永远持续下去,就像流感一样,就像肺炎球菌病一样。这不仅因为人们可能需要定期(打加强针)应对当前的毒株,还因为可能出现新的变异病毒,届时就像应对流感一样改进疫苗。
我不知道未来会不会是这样,我只知道,我们正在为相关情况做准备。所以说,公司正努力加强长期实力,确保完善流程。如果出现变异病毒也能迅速应对(我之前说过,六周或两个月内就可以)。我们也在制造更适合运输的疫苗,避免冷链出现问题。虽然研发很成功,但问题仍旧很复杂,成本也很昂贵。
顺便说一句,辉瑞承担了运送疫苗的所有费用。如果我们能找到更好的解决办法,对于达到业务最低目标将大大有利。
谈谈流感吧。几十年来,人们一直在急切地寻找“通用疫苗”,就是能应对每个季节出现的各种流感病毒的疫苗。在新冠危机之前,辉瑞公司就在跟BioNTech合作开发mRNA流感疫苗。能给出具体时间表吗?
我希望比之前计划快得多。因为现在已经证明我们能让不可能成为可能。另外,过去九个月里,我们积累了RNA技术方面的科学知识,正常情况下积累相关知识需要很多年。
现在我不想承诺流感疫苗研发的具体日期,但计划是以比平时快得多的速度(推向市场)。现在很多情况下,流感疫苗有效性只有40%或50%,我们的目标是研制对流感有效性超过90%的疫苗。届时将影响整个行业,我们希望能尽快做到。
考虑到癌症是遗传性疾病,mRNA平台会不会在个体化、靶向癌症药物中发挥作用?想必,快速研制个体化靶向药物的原则也可应用。
完全没问题。事实上,BioNTech大部分工作都在癌症领域,我相信mRNA技术可为癌症治疗开辟很多新途径。
你的职业生涯是从兽医开始的,现在大部分时间都花在人类疾病上。研究动物健康是不是能帮你看到其他人可能忽视的事?
我相信每一点不同寻常都能带来不同的视角。正如你提到,我是兽医,所以我了解科学,从而能够更好地与药物研发团队沟通。我还曾在辉瑞动物健康部门工作(后来分拆成Zoetis公司),11年前我转到人类健康部门时,我发现当时的制药巨头非常注重品牌,确实品牌非常重要。而在动物卫生领域不会这样,兽医行业重要的是顾客——是主人和狗。
我的出身也给了我一些特别的视角,由于我来自希腊这样有着辉煌历史,现实中在国际谈判桌上重要性却不大的小国家,你要学会如何去战斗,过程其实并不容易。
大屠杀期间希腊犹太人几乎灭绝,我身为犹太人也学会了适应,在社会上要懂得灵活应对才能生存。我母亲被捕后活了下来,父亲躲起来也成了幸存者。他们的家人命运却不一样,兄弟和父母都被杀死了。
我在辉瑞工作期间,曾在五个国家的八个城市生活,从中也体会到了多样性的力量,也感受到每种文化都是独一无二的,从而能贡献一些价值。由于我的自身经历,因而对此非常敏感。所有种种都帮我形成自己独有的视角,我认为所有经历都是有帮助的。
补充信息
(1) 收到的信息:传统疫苗使用失去部分活性,或完全失去活性的病毒激活免疫反应,而利用信使RNA的疫苗不一样,主要通过指示细胞制造与病毒相关的无害蛋白质,从而向免疫防御系统发出警报。
(2)连续五年年收入增长:公司指出,虽然辉瑞的生物制药业务强劲增长,然而之前Upjohn部门(最近先被迈兰制药剥离又合并)收入下降,2019年与葛兰素史克成立了消费医疗合资企业,增长都被抵消。
百时美施贵宝:19.0%
艾伯维:13.2%
默沙东:3.6%
强生:3.3%
礼来:3.3%
阿斯利康:0.7%
辉瑞:0.3%
(来源:标普环球)
(3)梦之队:疫情之前,辉瑞和BioNTech正合作研发流感疫苗。“现在很多情况下,流感疫苗有效性不到50%,”艾伯乐说。随着新冠疫苗研制成功,他预计两家合作伙伴“将成功研发出有效性最终超过90%的流感疫苗。”
(4)推动的赞助者:几家美国机构资助了规模比辉瑞小得多的Moderna公司,协助基于mRNA的新冠疫苗研发工作。Moderna疫苗获得食品药品管理局紧急使用授权比辉瑞疫苗晚了一周。
(5)从实验室到物流:辉瑞已向全球10000多个接种点,提供了超过5000万剂疫苗。
(6)仪表盘灯光下:数字并非是估计值。辉瑞通过实时仪表盘跟踪运送疫苗的实际成功率,仪表盘通过全球定位系统监控每个疫苗物流箱的位置和温度。
(7)动物精神:艾伯乐拥有执业兽医和博士学位,曾在希腊一所大学医院从事兽医产科工作5年,专长体外受精、人工受精和胚胎移植等。
(8)希腊悲剧:艾伯乐说,“在我家乡萨洛尼卡曾经有55000犹太人,大屠杀中幸存者只有2000人。后来很多人离开了。等我长大后,我们社区大概700到800人,但占了全城犹太人口的一半。”(财富中文网)
本文刊载于《财富》杂志2021年2月/3月刊,标题是《对话:艾伯乐》。
译者:冯丰
审校:夏林
As the pandemic took hold last spring, scientists at Pfizer set out to, in the words of CEO Albert Bourla, “make the impossible possible.” Now, on the heels of achieving just that—developing the world’s first COVID-19 vaccine with breakneck speed—the leader of the 172-year-old drugmaker talks about the clash of science and politics, drug prices, and his next impossible task.
This edited Q&A has been condensed for space and clarity.
Going all in on science
In early March, 2020, barely a year into your role as CEO, you made a near-instant decision to put some $2 billion of Pfizer’s money at risk to develop a coronavirus vaccine. What drove you to make that giant wager?
Bourla: It was a massive bet, but it was a very necessary one. There are not many companies that have the kind of end-to-end capabilities in vaccines that Pfizer has—ones that can start from early research and go all the way into not only manufacturing, but also distribution, which is challenging. So the question in my mind was, “If not us, then who?”
There are a slew of proven ways for constructing vaccines, but you chose to go with mRNA¹, a technology that had never before produced an approved vaccine. Why?
I knew that we were working with mRNA in flu [through our partnership with German firm BioNTech]. We had adenoviruses that we continue to work with in making vaccines for other diseases. We had recombinant proteins, you name it. But my team [led by head of vaccine research Kathrin Jansen] went through each technology, and said our recommendation is to go with mRNA, which could be scaled up very quickly once it was developed. It’s true that there had been no vaccine made before with mRNA technology—but if we are successful, then ours would be the first.
My team wanted to get started very fast. And BioNTech [CEO Ugur Sahin, who had reached out to Jansen in a March 1 phone call] also said they wanted to do it very fast. So we started investing, and they started sharing their data with us—without even a contract.
Your day job, of course, is to find solutions at Pfizer, where you’ve been trying to jump-start growth. You’ve projected annual revenue growth will reach 6% soon. That’s well above where the company has been for the last couple of years.² Are you still confident in that trajectory?
I’m very confident now. And also, I want to say the projection is for “at least 6%” revenue growth. The 6% is not the ceiling, it’s the floor. And I’m very confident—excluding anything coming from the COVID-19 vaccine—that the remaining segments of the business will deliver these numbers. And to that we need to add whatever the final impact of the COVID vaccine will be. We haven’t released any projections for that—though I believe on revenues, we will be higher than $3 billion.
The need for speed was one reason to go with an mRNA vaccine. Another benefit is that you can change the genetic recipe for the vaccine on the fly—something that may be necessary as the virus continues to mutate and more variants emerge.
Exactly. Speed was of the essence and flexibility was of the essence. This was exactly the reason why we’ve chosen this for flu.³ Flu has the same characteristics. Every year is a different flu. So every year the vaccines that we’re getting for flu are different from the year before. [With other technologies] each takes months to develop. The RNA vaccines could disrupt that, because you can do in weeks what you’d need months to do in the other cases.
The current coronavirus variants that have emerged are causing alarm. How effective is Pfizer’s vaccine against these mutant strains?
We are quite confident right now that we can neutralize these variants. We have proved that in the lab—and this experiment that we did in our own labs has been already replicated in multiple labs in universities and hospitals. Right now we are covering both of the new variants [that have emerged in the U.K. and South Africa]. I think the fundamental question is, What are the chances that a new mutation that will not be covered by the vaccine emerges? Theoretically, it’s a very possible scenario. If you protect a very big part of the population, and if there is a strain that emerges that can use this [vaccinated] pool of population to replicate while the current strains cannot, obviously this will overtake the original. So it’s not a certainty, but it is now, I believe, a likely scenario. But that proves even more the case for an mRNA vaccine—because now you can very quickly develop a new version of the vaccine that either adds to the current immunogenicity or creates a very different one that can cover the new mutations as well.
How quickly is “quickly”?
That will depend on multiple factors. One of them, it is the regulatory framework. But I believe we will be able within two months to have it. And, of course, we would still likely have to manufacture at risk.
Speaking of risk, you made a second big bet not to take any government money to develop the vaccine, as some of your competitors did.
The government said, “We can finance this.” But when the offer came, I thought a little bit what would happen if we take the money because it was the easiest thing to take. I realized that if the government gives you money, there’s no way that they will not want a seat at the table. “How are you going to do it?” they’ll ask. “How will you use the money? Give us a report.” Within a massive company like Pfizer, we have a lot of bureaucracy to deal with. I was betting that I would take control, so as the ultimate decision maker in the company I would waive all bureaucracy. My goal was to say, “You talk to me directly. I’m replacing all governing bodies. I’m making the decisions.” But I couldn’t do that if I was taking the government money. I knew that we’ll never be able to make the impossible possible if we didn’t do that. Keep in mind that we started much later than Moderna⁴, for example. But also we didn’t need the money. I’m sure Moderna needed it. Now, if we failed, was it going to be very painful? Absolutely. But if we failed, was that going to be the end of Pfizer? Absolutely not. This is why I was put in this position: to be able to take the right risk—not to be reckless, but also not to be conservative and not move when the world needs us.
For all the logistical feats you’ve pulled off⁵, there has been widespread frustration with the vaccine rollout in general. What’s gone wrong?
Look, there are two phases. There is the phase that I was worried about a lot, where Pfizer is sending the vaccine to vaccination centers in every country that has asked. That is our responsibility and fortunately we were able to do that very difficult logistical step quite successfully. We were able to see almost 99.99%⁶ successful shipments—on time without any issues with the quality, because we were monitoring the temperatures on every single box that we sent. But a lot of the countries, including the U.S., were not ready to distribute those vaccines. They didn’t have enough capacity in the vaccination centers. I’m sure—and I hope—that all of them will get their act together. They will change their plans and they will be able to dramatically increase the vaccination rates. And then, if they do that, we may have a period that we are the bottleneck and we need to produce much more, and we are preparing for that. We announced recently that we are increasing our expected production this year from 1.3 billion to 2 billion doses.
Everything is politics
As complex as the task of making and distributing this novel vaccine has been, you’ve had to deal with something even more challenging over the past year: politics. That came the moment you suggested your vaccine might be available this past October and you found yourself at the center of a bruising presidential campaign fight.
It was a whole different game—completely different than what I was expecting. And let me clarify something. The October timeline was the one I’d set in March with my team when I pushed them to go as fast as they possibly could. I was thinking that October is the flu season—without even thinking, of course, that in November we have elections. Suddenly it became the biggest political issue. It was shocking when I heard the first presidential debate and COVID and the vaccine were being discussed in political rather than in scientific terms. This is when I made the statement the next day that some people want us to go faster, some people want us to do it slower. I’ll tell you, we’ll go at the speed of science. And so be it. And then, the vaccine ended up coming a little bit after the November election. And now, what for some had been “too early,” for others became “too late.” Well, what can we do? I tried hard to navigate this political minefield. And one of the reasons why we didn’t take the government money in the first place was that. Because if you take governmental money, then everything that you do becomes even more politically charged.
You called Johnson & Johnson CEO Alex Gorsky and discussed asking other leaders in the pharmaceutical industry to push back as a group on the politicization of the vaccine effort. What prompted that—and how did it play out?
It was at a time when some were publicly accusing the FDA as being “deep state.” I started getting very worried because the politicization of the potential successful vaccine had already started. And that had created a lot of confusion for people and a lot of doubts. People were wondering: Is this going to be the Trump vaccine or is it going to be a real vaccine—a scientific vaccine? And the only one who could be the arbitrator there—the one who could be the judge—was the FDA, which is renowned for its science and integrity all over the world. They are the agency of reference, indisputably. So I was worried that an attack on FDA was also an attack on the independence and scientific integrity of the vaccine effort itself. Alex Gorsky is a good friend, and we talk often on multiple topics—and so I raised this concern with him. I said I thought we needed to do something: that we needed to make a statement ourselves that, no matter what, we will never cut corners—that we’ll follow the FDA guidelines no matter how much pressure someone might put on us, political or otherwise. Immediately he said, “You are right, this is what we need to do.” And then I said, “Why don’t we write something?” And within the next day, I think, I sent him a version of a statement and he sent it back. Then I said, “We need everybody to sign.” So we made a list of all the companies [in the industry], I took half and he took half. And then we started making phone calls. Everyone accepted immediately.
There’s a new administration in the White House and a new Congress. Sounds like a good time to push for some long-term solution on drug pricing—an issue that continues to dog your industry.
Let me first say that I’m a very strong believer that reform is needed. The current status quo is not sustainable and it’s not desirable. The vast majority of my peers are already in this column as well. Everybody says that we need to make changes. But those changes, I believe, have to have two fundamental pillars: They need to be pro-innovation and pro-patient. There is of course a major debate in the U.S. over drug pricing. But there are two different aspects to drug prices: One is the cost of medicines to the system, for example, to Medicare, the federal budget. The second is, what is the cost of medicines to individuals—the person who goes to the pharmacy and has to pay something out of his pocket? Those two are very different. The first one [how much the system is paying for medicines] represents 12% of the overall health care cost. So by definition, it cannot be the “big” problem, okay?
But when it comes to patients—the people who buy their medicines—this is by far their biggest challenge. Because right now, Americans are paying for their medicines as if they don’t have insurance—even when they do. They pay a huge amount out-of-pocket. That needs to change. Now, to move costs out of the patient’s hands, then someone has to pay, because it’s not a zero sum. We are willing to take over a very big part of out-of-pocket costs for the patients right now. I don’t say—and I don’t think anyone would say—that it’s fair that we take all of it. But we are willing to take our fair share and even more. But this is where the money should go. I don’t think that the money should go to cover the black hole of federal budgets that will grow and grow. But in any case, we must find a solution and we must find it now—this year.
How long do you see COVID as being a continued challenge for society—and what does that mean for Pfizer’s business?
Look, you can never be certain—and still, for the time being when it comes to investors, we will treat the vaccine as separate item. So we will give visibility to our investors about our base business contribution, top line, and bottom line—and also the top line and bottom line for the COVID-19 business. Because it could be a one-off, two years, three years, something like that. But the truth is that a lot of indicators are telling me that it could be a forever bit of business, like we have for flu, and like we have for pneumococcal disease. And that’s not only because we may have to repeat [booster shots] periodically, for the current strains, but also because of the chance that we will have new mutants and variants coming out so that you will have to evolve your vaccines, as happens with flu. I don’t know if that’s going to be the case. What I do know is that we are preparing for this scenario. So we are making sure that we are building our capacity for the long term. We are making sure that we are refining our process—so if variants come out, we’ll be able to address them in a very quick manner (as I said, in six weeks or two months). And we are also building more transportation-friendly variations of the vaccine so that we can avoid the cold chain complication. Although it’s very successful, it’s still a complication and very expensive for us, by the way, because we assume the full cost of transporting the vaccine. If we can find a better solution, that will contribute significantly to the bottom line.
Let’s talk for a minute about flu. The quest for a “universal vaccine”—one that can neutralize whichever strain of flu emerges each season—has been eagerly sought for decades. Pfizer was working with BioNTech on developing an mRNA flu vaccine before the COVID crisis. What’s the timetable for that?
I hope much faster than our previous plan. Because now we have proven that we can make the impossible possible. Also, the truth is that, in the last nine months, we have accumulated scientific knowledge and expertise on the RNA technology that would have taken years to accumulate under normal circumstances. So I don’t want to give a specific commitment date right now for a flu vaccine, but our plan is to bring it [to market] much, much faster than we normally would do. And the plan is exactly what you said. Right now, the flu vaccines, in many cases, have a 40% or 50% efficacy. Our aim is to bring a vaccine that will have more than 90% efficacy against flu. That would be a game changer. And we want to be able to do it very quickly.
Will the mRNA platform play a role in individualized, targeted cancer drugs, given that cancer is a genetic disease? Presumably, the principle of creating individualized targeted medicines very quickly would apply there too.
This is absolutely true. And in fact, most of the work pre-COVID of BioNTech was in the cancer field. I believe that the mRNA technology will open a lot of new avenues in cancer therapy.
You began your professional career as a veterinarian⁷ and now spend most of your time focused on human disease. Has studying animal health helped you see things in your current role that others might not?
I believe everything that is a little bit out of the ordinary helps bring different perspectives. As you say, I’m a veterinarian and that lets me understand the science so I can better communicate with our drug development teams. I also worked in the animal health group of Pfizer [since spun off as Zoetis], and when I moved to the human health side—11 years ago—I realized that Big Pharma, at the time, was very much brand focused. It was the brand that mattered. That was never the case in animal health. There, it was the customer who mattered—it was the owner and the dog; it was the veterinarian.
Also, I think coming from a small country like Greece—one with glorious history, but which in the current reality doesn’t have a very big seat at the international table—has brought some perspective. You learn how to fight, [you know] it’s not going to be easy. Being Jewish in a country where the Jewish population was almost exterminated during the Holocaust taught me to be adaptive, and to be much more flexible in society so you can survive. My mother was arrested and survived. My father was hiding and survived. But it was not the same with their families. So brothers, parents, they were exterminated. That gave me an identity.⁸ The fact that in my career in Pfizer I lived in eight different cities in five different countries has also made me appreciate the power of diversity and how every culture is unique and brings things to the table. My own experience taught me to be very sensitive to that. All of that gave me perspectives that have helped me become who I am, and I think everything helped.
Between the lines
(1) Message received: Unlike traditional vaccines that use part of a disabled or dead virus to illicit an immune response, these vaccines use messenger RNA to instruct cells to make a harmless protein associated with the virus—which, in turn, alerts immune-system defenders.
(2) Annualized trailing five-year revenue growth: Strong growth in Pfizer’s biopharma business, the company notes, was offset by declining revenues within its former Upjohn unit (recently spun off and combined with Mylan) and by a consumer healthcare joint venture with GSK in 2019.
Bristol-Myers Squibb: 19.0%
AbbVie: 13.2%
Merck: 3.6%
Johnson & Johnson: 3.3%
Eli Lilly: 3.3%
AstraZeneca: 0.7%
Pfizer: 0.3%
(Source: S&P Global)
(3) Dream team: Before COVID-19, Pfizer and BioNTech were working on developing a flu vaccine. “Right now, flu vaccines, in many cases, have less than a 50% efficacy,” says Bourla. With the success of their coronavirus vaccine, he expects the partners “to bring a vaccine that will have almost ultimate efficacy of more than 90% against the flu.”
(4) Booster benefactors: Several U.S. agencies helped Moderna, a much smaller company than Pfizer, finance the development of its mRNA-based coronavirus vaccine. The Moderna vaccine received emergency use authorization from the FDA one week after Pfizer’s.
(5) From lab to logistics: Pfizer has delivered more than 50 million doses to more than 10,000 vaccination points around the world.
(6) By the dashboard light: The figure is not an estimate. Pfizer tracks its actual success rate in shipping vaccine through a real-time dashboard that monitors the location (by GPS) and temperature of each box.
(7) Animal spirits: Bourla, who holds a DVM and a Ph.D., practiced veterinary obstetrics at a university hospital in Greece for five years, specializing in in vitro fertilization, artificial insemination, and embryo transfer.
(8) Greek tragedy: “In my city of Thessaloniki,” says Bourla, “there were 55,000 Jews and only 2,000 survived the Holocaust. And then actually many of them left. So eventually, when I grew up, we had a community of 700 or 800 people in a city where we once made up half of the population.”
This article appears in the February/March 2021 issue of Fortune with the headline, "The Conversation: Albert Bourla."