经济学人：
WEIGHT-LOSS drugs called GLP-1 agonists help users shed fat, and with it the negative health effects of obesity. This can have life-changing effects for the people who take them. It is also increasingly affecting the lives of corporate citizens. Since June 2021, when Wegovy, the first GLP-1 slimming jab, was launched in America, the market value of WW (formerly Weight Watchers) has crashed by 90%. On February 28th Oprah Winfrey announced that she would leave the dieting firm’s board and sell all her shares in order to avoid a conflict of interest around her use of GLP-1s. Food giants such as Nestlé are already planning for a future where the drugs dampen demand for sugary snacks. Bosses of consumer-goods firms brought up weight-loss drugs twice as often in the last full set of quarterly earnings calls, in late 2023, as they had in the previous one (see chart 1).
称为 glp-1 激动剂的减肥药物可以帮助使用者减少脂肪，并消除肥胖对健康的负面影响。这会对服用它们的人产生改变生活的影响。它也越来越多地影响着企业公民的生活。自 2021 年 6 月首款 glp-1 减肥针 Wegovy 在美国上市以来，ww（前身为慧俪轻体）的市值已暴跌 90%。 2 月 28 日，奥普拉 · 温弗瑞 (Oprah Winfrey) 宣布，她将离开这家节食公司的董事会，并出售所有股份，以避免因使用 glp-1 产生利益冲突。雀巢等食品巨头已经在规划未来，药物将抑制对含糖零食的需求。在 2023 年末举行的上一次全套季度财报电话会议中，消费品公司的老板们提到减肥药的频率是上一次的两倍（见图 1）。
image: The Economist 图片来源：《经济学家》The drugs’ biggest impact so far, though, has been on their makers. Sales of Wegovy, developed by a Danish firm called Novo Nordisk, swelled from $876m in 2022 to $4.5bn in 2023. The company expects double that this year. Zepbound, introduced in America in November by Eli Lilly, an American pharma giant, is expected to generate $2.9bn in sales in its first full year. Bloomberg, a data provider, predicts that by 2030 yearly sales of weight-loss medications will reach a staggering $80bn, putting them among the biggest classes of drugs in history. Eli Lilly and Novo Nordisk are expected to corner more than 90% of the market (see chart 2).
不过，迄今为止，这些药物最大的影响还是对其制造商造成的。由丹麦诺和诺德公司开发的 Wegovy 销售额从 2022 年的 8.76 亿美元增至 2023 年的 45 亿美元。该公司预计今年将增长一倍。 Zepbound 由美国制药巨头礼来公司 (Eli Lilly) 于 11 月在美国推出，预计首个全年销售额将达到 29 亿美元。数据提供商彭博社预测，到 2030 年，减肥药物的年销售额将达到惊人的 800 亿美元，跻身历史上最大的药物类别之列。礼来公司 (Eli Lilly) 和诺和诺德 (Novo Nordisk) 预计将占据 90% 以上的市场份额（见图 2）。
Investors’ appetite for the duopoly’s shares has been as insatiable as dieters’ for its products. In the past three years Novo Nordisk’s market capitalisation has expanded more than threefold, to $560bn, turning it into Europe’s most valuable company. Eli Lilly is worth $740bn, more than twice what it was at the start of 2023 (see chart 3). They are now the world’s two biggest pharma firms by market value. There is excited talk of the industry’s first trillion-dollar company—and the second. To live up to those lofty expectations, however, Eli Lilly and Novo Nordisk must make enough of the drugs to meet demand, widen the pool of patients and fend off a clutch of challengers.
投资者对双头垄断股票的胃口就像节食者对其产品的胃口一样。过去三年里，诺和诺德的市值增长了三倍多，达到 5600 亿美元，成为欧洲最有价值的公司。礼来公司的市值为 7400 亿美元，是 2023 年初的两倍多（见图 3）。按市值计算，它们现在是世界上最大的两家制药公司。人们兴奋地谈论着业界第一家和第二家价值数万亿美元的公司。然而，为了不辜负这些崇高的期望，礼来公司和诺和诺德公司必须生产足够的药物来满足需求，扩大患者群体并抵御一批挑战者。
image: The Economist 图片来源：《经济学家》GLP-1 agonists are extremely effective and relatively safe. Originally introduced to help diabetic patients by promoting insulin production, they regulate the body’s response to eating and create a feeling of fullness that suppresses appetite. Patients who take them lose more pounds than people on other weight-management plans. In clinical trials users of Wegovy shed about 15% of their body weight on average. Those on Zepbound lost around 20%.
glp-1 激动剂极其有效且相对安全。它们最初是通过促进胰岛素的产生来帮助糖尿病患者的，它们可以调节身体对饮食的反应，并产生抑制食欲的饱腹感。服用这些药物的患者比接受其他体重管理计划的患者减掉的体重更多。在临床试验中，Wegovy 的使用者平均体重减轻了约 15%。 Zepbound 上的用户损失了大约 20%。
Given that 2.7bn people, or 38% of those aged older than five, are obese or overweight, according to the World Obesity Federation, the drugs are also in high demand. Because the injections must be taken weekly rather than just once, the more people start treatment, the faster total demand rises. And it is already rising so fast that Eli Lilly and Novo Nordisk are struggling to meet it.
根据世界肥胖联合会的数据，鉴于 27 亿人（五岁以上人口中的 38%）肥胖或超重，这些药物的需求也很高。由于注射必须每周进行一次，而不仅仅是一次，因此开始治疗的人越多，总需求增长得越快。而且它的增长速度如此之快，以至于礼来公司和诺和诺德公司都在努力应对。
image: The Economist 图片来源：《经济学家》The drugs require two main components: the active ingredient and the “skinny pens” that patients use to inject the medicine. Right now both are hard to find. Neither the Danish firm nor its American rival has explained why they cannot get hold of more of the necessary chemicals, but it is clearly a problem. A shortage of semaglutide, which gives Wegovy its powers, has forced Novo Nordisk to push back the launch of a pill version of Wegovy, which works as well as the shot, is easier to make and less unpleasant to administer, but which requires 20 times the amount of the active ingredient.
这些药物需要两个主要成分：活性成分和患者用来注射药物的 “细笔”。现在两者都很难找到。这家丹麦公司及其美国竞争对手都没有解释为什么他们无法获得更多必要的化学品，但这显然是一个问题。索马鲁肽的短缺迫使诺和诺德推迟了药丸版 Wegovy 的上市，这种药物的效果与注射剂一样，更容易制作，管理起来也更容易，但需要 20 次注射活性成分的量。
Making enough of the skinny pens for Wegovy and Zepbound has also been a challenge. The devices come from specialised “fill-finish” factories. Eli Lilly and Novo Nordisk are pouring out billions of dollars to boost supply by teaming up with manufacturers or building their own capacity. In November the American firm announced it would spend $2.5bn on a new factory in Germany, and Novo Nordisk said it would invest $6bn in expanding capacity at its Danish site. In February Novo Nordisk’s parent company agreed to pay $16.5bn for Catalent, a big American manufacturer, to boost production for America’s gargantuan market. Despite these investments, analysts expect demand to outstrip supply for at least a few years.
为 Wegovy 和 Zepbound 制造足够的细钢笔也是一个挑战。这些设备来自专门的 “填充加工” 工厂。礼来公司和诺和诺德公司正投入数十亿美元，通过与制造商合作或建设自己的产能来增加供应。去年 11 月，这家美国公司宣布将斥资 25 亿美元在德国建设一家新工厂，诺和诺德表示将投资 60 亿美元扩大丹麦工厂的产能。今年 2 月，诺和诺德的母公司同意斥资 165 亿美元收购美国大型制造商 Catalent，以提高美国庞大市场的产量。尽管有这些投资，分析师预计至少在几年内需求将超过供应。
The limited production capacity has helped the companies in one way, by masking another problem. So far only half of the 110m obese Americans have access to the drugs through their health insurance. To hit the rosy revenue forecasts, Eli Lilly and Novo Nordisk need to make their treatments available to a wider group of patients. Medicare, a government health-care programme for the elderly, is prohibited by law from covering weight-loss drugs. Private health insurers are put off by the medicines’ costs. Even though discounts mean they typically pay around 60% of Wegovy’s list price in America of some $16,000 a year, many insurance firms are reluctant to cover an expensive drug that must be taken indefinitely.
有限的产能在某种程度上帮助了这些公司，同时也掩盖了另一个问题。到目前为止，1.1 亿肥胖美国人中只有一半能够通过健康保险获得这些药物。为了实现乐观的收入预测，礼来公司和诺和诺德需要向更广泛的患者群体提供他们的治疗方法。医疗保险是一项针对老年人的政府医疗保健计划，法律禁止其承保减肥药物。私人医疗保险公司因药品成本而望而却步。尽管折扣意味着他们通常支付 Wegovy 在美国标价的 60% 左右（每年约 16,000 美元），但许多保险公司不愿意承保必须无限期服用的昂贵药物。
To bring insurers on board, the duo are running trials to prove that GLP-1s do more than just help people lose weight. A trial by Novo Nordisk found that Wegovy lowers the risk of major heart problems by 20%. Eli Lilly is conducting a giant trial with 15,000 participants, set to finish in 2027, which studies the effect of tirzepatide, the active ingredient in Zepbound and Mounjaro, a related diabetes medicine, on the overall health and lifespan of obese adults. There is evidence to suggest that GLP-1s also help with conditions such as sleep apnea, chronic kidney disease, Alzheimer’s disease and fatty liver disease. The use of GLP-1 drugs to treat these illnesses has not yet been approved by regulators. But David Risinger of Leerink Partners, an investment bank, believes that as more health benefits emerge, it will become hard for insurers to deny coverage.
为了让保险公司加入进来，两人正在进行试验，以证明 glp-1 的作用不仅仅是帮助人们减肥。诺和诺德 (Novo Nordisk) 的一项试验发现，Wegovy 可以将严重心脏问题的风险降低 20%。礼来公司正在进行一项有 15,000 名参与者参加的大型试验，预计将于 2027 年完成，研究 Zepbound 和 Mounjaro（一种相关糖尿病药物）的活性成分替西帕肽对肥胖成年人整体健康和寿命的影响。有证据表明，glp-1 还有助于治疗睡眠呼吸暂停、慢性肾病、阿尔茨海默病和脂肪肝等疾病。使用 glp-1 药物治疗这些疾病尚未得到监管机构的批准。但投资银行 Leerink Partners 的 David Risinger 认为，随着更多健康福利的出现，保险公司将很难拒绝承保。
Eli Lilly and Novo Nordisk may in time deal with their capacity and coverage problems. That still leaves a third challenge: competition. The booming market has unleashed a flood of wannabes, from big pharma to biotechnology startups. Bloomberg estimates that close to 100 candidates for weight-loss drugs are in various stages of development. Most imitators are refining the GLP-1 approach to craft drugs that outdo existing ones by delivering more weight loss or easier use.
礼来公司和诺和诺德公司可能会及时处理其容量和覆盖范围问题。这仍然留下了第三个挑战：竞争。蓬勃发展的市场催生了大批追随者，从大型制药公司到生物技术初创公司。彭博社估计，近 100 种候选减肥药物正处于不同的开发阶段。大多数模仿者正在改进 glp-1 方法来制造药物，通过提供更多的减肥或更容易使用来超越现有的药物。
Combo meal 套餐
One idea to boost efficacy is to combine GLP-1 with other agonists. Zepbound already uses one called GIP along with GLP-1 to increase energy expenditure, decrease fat accumulation and reduce nausea. Viking Therapeutics, an American biotechnology company, uses a similar cocktail. On February 27th it shared trial data which showed that its anti-obesity medicine helped patients lose more weight even than Zepbound. Viking’s share price more than doubled. A drug in development by Boehringer Ingelheim, a German drug company, and Zealand Pharma, a Danish biotech firm, uses another agonist called Glucagon in combination with GLP-1 to ensure weight loss and fight liver diseases.
提高疗效的一种想法是将 glp-1 与其他激动剂结合起来。 Zepbound 已经将一种名为 gip 的药物与 glp-1 一起使用，以增加能量消耗、减少脂肪堆积并减少恶心。美国生物技术公司 Viking Therapeutics 使用类似的鸡尾酒。 2 月 27 日，该公司分享了试验数据，显示其抗肥胖药物帮助患者减掉的体重甚至比 Zepbound 还要多。维京公司的股价上涨了一倍多。德国制药公司勃林格殷格翰 (Boehringer Ingelheim) 和丹麦生物技术公司 Zealand Pharma 正在开发的一种药物，使用另一种名为胰高血糖素的激动剂与 glp-1 结合，以确保减肥和对抗肝脏疾病。
Other rivals, such as Pfizer, an American drug giant, and Carmot Therapeutics, a biotech startup which in December was scooped up for $2.7bn by Roche, a Swiss behemoth, are focusing their efforts on doing away with needles. Besides being cheaper to make and easier to pop, oral drugs do not need refrigeration as many injectables do. This makes them more suitable than jabs for patients in poorer countries, many of which also face an obesity crisis but lack robust “cold-chain” logistics. Ray Stevens, chief executive of Structure Therapeutics, another biotech firm pursuing oral weight-loss drugs, believes that it is still “early innings”. It will be a while before pharma’s weight-loss winners are decided, he says.
其他竞争对手，例如美国制药巨头辉瑞（Pfizer）和生物技术初创公司卡莫特治疗公司（Carmot Therapeutics），去年 12 月被瑞士巨头罗氏公司（Roche）以 27 亿美元收购，它们正集中精力废除针头。除了制造成本更低且更容易流行之外，口服药物不像许多注射剂那样需要冷藏。这使得它们比疫苗更适合较贫穷国家的患者，其中许多国家也面临肥胖危机，但缺乏强大的 “冷链” 物流。另一家研发口服减肥药的生物技术公司 Structure Therapeutics 的首席执行官雷 · 史蒂文斯 (Ray Stevens) 认为，这仍处于“早期阶段”。他说，制药公司的减肥获胜者还需要一段时间才能确定。
The two pioneers have a head start, however. The patents for Wegovy and Zepbound expire only in 2032 and 2036, respectively. No rival product is about to go on sale. Developing a new drug takes on average nine years, and even those now in early trials are unlikely to be available before 2027. Most important, the prospect of years of healthy profits has not turned either leader into a couch potato. On the contrary, the two companies are innovating furiously in order to maintain their edge over potential competitors—and to steal a march over one another.
然而，这两位先驱者已经取得了领先优势。 Wegovy 和 Zepbound 的专利分别将于 2032 年和 2036 年到期。没有竞争对手的产品即将上市。开发一种新药平均需要 9 年时间，即使是那些目前处于早期试验的药物也不太可能在 2027 年之前上市。最重要的是，多年健康利润的前景并没有让这两家领先公司变成电视迷。相反，这两家公司正在疯狂创新，以保持相对于潜在竞争对手的优势，并抢先一步。
Already Eli Lilly has closed Novo Nordisk’s early lead thanks to Zepbound’s greater efficacy. The American drugmaker’s share price relative to its forecast profits in the coming year is almost twice that of its Danish rival. Novo Nordisk’s fortunes are much more closely bound up with GLP-1 than those of Eli Lilly, which also has money-spinners in cancer and immunology treatments. Novo Nordisk hopes its pill and seven other related drugs in various stages of trials will help it regain its lead. Eli Lilly, for its part, has six drugs in the works, including a promising pill of its own in late-stage trials that, if all goes well, could be in pharmacies by 2026. Only one of them can be the first to a trillion dollars. But as they race, millions of patients will be the real winners. ■
由于 Zepbound 更高效，礼来公司 (Eli Lilly) 已经缩小了诺和诺德 (Novo Nordisk) 的早期领先优势。这家美国制药商的股价相对于来年预测利润的比例几乎是其丹麦竞争对手的两倍。与礼来公司相比，诺和诺德公司的命运与 glp-1 的联系更为紧密，礼来公司在癌症和免疫学治疗领域也拥有赚钱的机会。诺和诺德希望其药物和其他七种处于不同试验阶段的相关药物将帮助其重新获得领先地位。礼来公司则有六种药物正在研发中，其中包括一种处于后期试验中的有前途的药物，如果一切顺利，可能会在 2026 年上市。只有其中一种可以成为第一个上市的药物。万亿美元。但当他们比赛时，数百万患者将成为真正的赢家。 ■
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