In praise of Big Pharma’s me-too drugs
If there is one product that annoys people, it is the me-too drug. Pharmaceuticals companies should take advantage of the genetics revolution to find cures for intractable diseases such as cancer and cystic fibrosis, the critics moan. Instead, they spend billions trying to match the pills already made by others.
Blood cholesterol too high? Try Pfizer's Lipitor, Bristol-Myers Squibb's Pravachol, Novartis's Lescol or AstraZeneca's Crestor. A few problems down below? No need to confine yourself to Viagra from Pfizer. Now there is Bayer's Levitra and Eli Lilly's Cialis. Painful joints? Take Celebrex or Bextra by Pfizer, Prexige by Novartis or Vioxx by Merck.
Actually, forget the last two, and maybe Bextra as well. Merck is in trouble after withdrawing Vioxx because it caused heart attacks, Novartis this week postponed its application to have Prexige approved by European Union regulators and Bextra is looking shaky on health grounds. The ranks of me-too Cox-2 inhibitors the class of pain-killer in question are thinning.
As this shows, drugs can make it through clinical trials only for side-effects to be discovered when they are prescribed to millions of patients. If all drugs in each therapeutic class were identical, Celebrex would now be off the market along with Vioxx. In fact, one pill can turn out to be safer than another. Indeed, without going into details about Levitra and Viagra, their effects can also vary.
So far, helped by a lax regulatory regime in the US, pharmaceuticals companies have managed to avoid too much direct comparison of me-too drugs. Face-offs are bad for business: for every winner, there is a loser. But the tightening of US supervision provoked by the Vioxx withdrawal, combined with efforts by insurers and governments to curb costs, will ensure that competition bites.
There is a tendency among the medical fraternity to tut-tut about the proliferation of drugs as unproductive and unnecessary. Marcia Angell, a former editor of the New England Journal of Medicine, argues in her book The Truth About Drug Companies that me-too drugs are symptomatic of Big Pharma's intellectual bankruptcy.
Dr Angell says there is “almost no evidence of price competition in the me-too business” and trials “almost never compare me-too drugs with one another for the same condition at similar doses”. One or two drugs would do: “I know of no rationale for, say, the seven brand-name Ace inhibitors that are sold to treat high blood pressure and heart failure.”
There is something to her critique. One of the attractions of me-too drugs has been that pharmaceuticals companies have been able to market them heavily in the US spending $3.3bn on direct-to-consumer advertising in 2003, and giving $16bn of free samples to doctors. This makes them look more like branded consumer goods companies than research-based scientific organisations.
But there are already signs of drug proliferation leading to falling prices. In Europe, the existence of alternative treatments has helped governments to cap prices. Pfizer is fighting a German proposal to pay the same for all cholesterol drugs, cutting the sum it gets for Lipitor by a third. Even in the US, drug companies increasingly have to compete to get their drugs on to approved prescription lists.
That means direct comparisons on both price and effectiveness. Despite the industry's traditional resistance to “head-to-head” trials, they are becoming more commonplace. Bristol-Myers Squibb financed a head-to-head study of Pravachol and Lipitor in an effort to displace the market leader, only to find this year that Lipitor worked better.
These market pressures are likely to be exacerbated by regulatory reforms. The Vioxx withdrawal has highlighted an anomaly in US drug regulation: while the Food and Drug Administration strictly oversees the trials leading up to the approval and registration of new drugs, it allows companies more room for manoeuvre once drugs go on sale.
The FDA's Office of Drug Safety, which should ensure the safety and efficacy of approved treatments, lacks clout. Most studies of these drugs are carried out by the companies that make them, not to test whether they are safe for approved uses, but to find new ones. As one witness to the Senate finance committee said, it was a “lucky break” that one such trial of Vioxx picked up its safety flaw.
There is bound to be stricter supervision now of drugs already on the market. This will in turn lead to direct comparisons of me-too drugs to see which one performs best and which is safest. The World Health Organisation has already suggested that European countries with national health systems should monitor the efficacy and safety of prescribed drugs to compare how they work.
Thus, while Dr Angell is correct that there has been too little competition among me-too drugs, those days are passing. From the perspective of drugs companies, this makes life trickier. Not only is the least safe drug in any class liable to be knocked out in the same way as Vioxx, but even safe ones will have to face off against each other to establish the best of all.
This may all sound terribly wasteful to a doctor, but it is the same thing that is good for consumers in other markets: open competition. The problem until now has not been too much of it, but too little. The last thing that a patient should want is a choice of only one drug. As the Vioxx withdrawal shows, me-too pills may inspire little affection, but they would be missed if they were not there.
为仿制药叫好
如果说有一种产品令人烦恼，那就是仿制药。批评者抱怨说，制药公司应利用遗传学革命之机，寻找治疗癌症和囊肿性纤维化等疑难重症的办法。可它们反而花费巨资，试图开发别人已有的药品。
胆固醇偏高怎么办？试试辉瑞制药（Pfizer）的立普妥（Lipitor）、必治妥施贵宝（Bristol-Myers Squibb）的普拉固（Pravachol）或阿斯利康（AstraZeneca）的可定（Crestor）。下边的东西有点问题？不必非用辉瑞的伟哥（Viagra），现在还有拜尔（Bayer）的乐威壮（Levitra）和礼来（Eli Lilly）的西力士（Cialis）。关节疼痛？那就用辉瑞的西乐葆（Celebrex）或伐地昔布（Bextra），诺华（Novartis）的Prexige，或者默克（Merck）的快确适（Vioxx）。
其实不必去管后面两种药物，或许连伐地昔布也不需要。快确适因会引发心脏病而被收回后，默克正陷入困境；本周，诺华推迟向欧盟监管机构提交Prexige的审批申请；而伐地昔布似乎也存在健康隐患。这类受到质疑的镇痛药――环氧合酶２（Cox-2）抑制剂的产品种类正在减少。
这说明，只有当药物应用于数百万患者并发现副作用后，才能通过临床试验。如果每一类治疗药物的全部产品都是一样的，市面上现在就看不到西乐葆和快确适了。事实上，一种药物可能比另一种更安全。确实，不必仔细了解乐威壮和伟哥就能发现，其药效也有所区别。
迄今，由于美国监管机制松懈，制药公司设法避开了对仿制药过于严格的直接比较。对企业来说，对抗没好处，有赢就有输。不过，受快确适被收回的影响，再加上保险商和政府力图降低代价，美国强化了监管，这必将引发残酷的竞争。
制药企业中出现了一种趋势，它们纷纷指责药品的扩散既无利可图，又毫无必要。《新英格兰医学杂志》（New England Journal of Medicine）前编辑玛西娅?安吉尔（Marcia Angell）在其著作《制药公司的真面目》（The Truth About Drug Companies）中辨称，仿制药是制药巨头知识创新枯竭的征兆。
安吉尔博士说，“几乎没有证据显示，模仿性药品存在价格竞争，”试验也“几乎从未以类似的剂量、在同样的条件下对仿制药进行过相互比较。”一、两种药物就足够了，“我不知道，比如说，为什么用于高血压和心力衰竭的血管紧张素转换酶（ACE）抑制剂要有7个品牌在销售。”
对她的批评有几种解释。仿制药的一大吸引力一向在于，制药公司在美国可以大力营销，2003年就花费了33亿美元用于直接面对消费者的广告，并免费给予医生价值160亿美元的药物样品。这使它们看上去更像知名的消费品公司，而非以研究为基础的科学机构。
但已有迹象表明，药物的扩散正导致价格下滑。在欧洲，多种治疗方法的存在有助于政府抑制药价。辉瑞正力图阻止德国的一项计划，该计划要对所有胆固醇药物设定同一价格，从而使其立普妥收入减少三分之一。即使在美国，制药公司也日益需要通过竞争，才能使其药物被批准为处方药。
这意味着对价格和药效的直接比较。尽管制药业有着反对“一对一”试验的传统，但这种做法正越来越普遍。为夺取市场领先地位，必治妥施贵宝出资对普拉固和立普妥进行了一对一研究，但今年的研究结果却表明，立普妥疗效更好。
监管制度的改革可能会加大这些市场压力。快确适的收回已凸显出美国药品监管的异常举动：尽管食品和药物管理局（Food and Drug Administration）严格监督涉及新药批准和注册的试验活动，但也给予制药公司在药品上市后进行调整的余地。
食品和药物管理局药品安全办公室本应确保被认可药物的安全性和有效性，但却缺乏影响力。大部分此类药物的研究均由生产该药物的公司承担，这些研究不是为了测试按照被认可的方法使用是否安全，而是为了开发新药。正如一位在参议院财政委员会作证的人所说，针对快确适的这类试验发现了安全漏洞，这是个“幸运的突破”。
对于已上市的药品，现在的监控必定会更严格。反过来，这将导致对仿制药的直接比较，以了解哪一个疗效最好，哪一个最安全。世界卫生组织（World Health Organisation）已提议，具备国民医疗体系的欧洲国家应监督处方药的药效和安全性，以比较其优劣。
因此，尽管安吉尔博士关于仿制药竞争过少的看法是正确的，但这种局面即将消失。在制药公司看来，这使其业务更加棘手。不仅各类药物中最不安全的产品很容易像快确适那样遭淘汰，甚至安全的药物也将不得不相互竞争，决出胜负。
对于医生，这一切听起来或许是废话连篇，但对其他市场的消费者却同样是有益的，这就是促进竞争。迄今问题一直不在于竞争太多，而是太少。病人决不希望只有一种药物可供选择。正如快确适收回所表明的，仿制药或许不会招人喜欢，但如果消失则会被人想念。
