Glaxo's Paxil Controversy Could Pose Risk for Investors
Paxil is one of the biggest drugs made by GlaxoSmithKline PLC, the global pharmaceuticals giant, raking in more than $3 billion a year in sales and helping millions of people in their fight against depression.
But the slow drumbeat of controversy that has swirled around the drug for years is likely to get louder over the coming months, which could give investors in Glaxo pause about the risks involved in holding the stock.
Some scientists and users long have argued that Paxil, which is sold as Seroxat in Europe, and related drugs cause serious withdrawal symptoms and, in some cases, trigger violence and suicidal behavior. Glaxo and other drug makers deny the claims. "I don't believe there's any credible evidence that [Paxil] causes suicide or aggression," says Alastair Benbow, Glaxo's head of European clinical psychiatry.
But the issue has recently come into sharper focus for both regulators and plaintiffs' lawyers -- and that attention is likely to increase, raising questions in investors' minds about what impact it may have on Paxil's future sales, Glaxo's finances and the company's stock.
United Kingdom regulators in June urged doctors not to prescribe Paxil to children because of data linking it to suicidal behavior in those under the age of 18. The U.S. Food and Drug Administration immediately sounded a similar warning. Now, U.K. regulators are in the midst of an extensive study of Paxil's effect on adults, which is due out early next year. Plaintiffs' lawyers, meanwhile, are preparing for more legal volleys against Glaxo.
No full-blown clinical test has yet been done that might settle the broader matter of Paxil's effects. But there is a lot at stake for the company.
"Paxil is clearly an important drug for them," said James Culverwell , a pharmaceuticals analyst at Merrill Lynch in London, who has a "buy" recommendation on the stock. (Merrill Lynch's Glaxo reports note that the firm expects to receive or intends to seek payment for investment-banking services within the next three months.) "What Glaxo's concerned about is that they don't want a big court case [because it could] tarnish the drug for the adult population" who take it.
The heightened debate over Paxil comes at a time when Glaxo, along with other global pharmaceutical companies such as Schering-Plough Corp. of the U.S. and AstraZeneca PLC of the U.K., are struggling to launch new big-selling drugs and offset anticipated sharp declines in sales because of competition from generics. Last year, Glaxo's sales rose 4% to ￡21.21 billion ($34.20 billion or �30.09 billion), well below the 12% gain of big rival Pfizer Inc.
In the past six months, Glaxo's shares have risen 8.5%, as the broad Dow Jones Stoxx 600 index of European companies rallied 11%. Still, burdened by concerns about the looming generic competition for several drugs, Glaxo shares remain relatively cheap, trading at about 16 times the company's earnings of the past 12 months, compared with about 21 for the industry, according to Reuters Research. Wednesday on the London Stock Exchange, Glaxo's shares fell 20 pence to ￡11.62.
Depending on how the increased focus on Paxil plays out, Glaxo may be forced to change the Paxil label to reflect any potential suicide-risk in adults, if that's what regulators find -- a move that could reduce prescriptions and eat into the drug's sales. A large chunk of the 30 million Paxil prescriptions made in the U.S. last year were written by doctors who were non-psychiatrists. These doctors might be less inclined to readily prescribe the drug if it carries a suicide-warning label.
And given the number of Paxil-related cases pending against Glaxo, the company may come under increasing pressure to enter into costly settlements with plaintiffs. "The numbers could be huge," says John Wilson, a fund manager at Standard Life Investments, one of the biggest Glaxo shareholders in the U.K. Although the issue "is in the background," he says it is worth considering because "the U.S. is such a litigious society."
The controversy over Paxil has been simmering for a while. Two years ago a Wyoming jury awarded $6.4 million against Glaxo after a man taking Paxil for two days killed several family members and then himself. Glaxo privately settled that case, and, since then, has quietly settled at least another two dozen, according to plaintiffs' lawyers.
"The company isn't just rolling over and getting out its checkbook" but recent decisions against Paxil "have increased public awareness," says Andy Vickery, attorney at Vickery & Waldner of Houston, who represented the plaintiff in the Wyoming case. The law firm in the past six months has filed five separate cases relating to Paxil and the risk of suicide or aggression, Mr. Vickery says. It also has settled about a dozen Paxil cases with Glaxo since the Wyoming verdict, he adds. Glaxo declined to comment on pending lawsuits related to Paxil or cases it has settled.
In the past year, law firm Baum, Hedlund, Aristei, Guilford & Schiavo, of Los Angeles, has filed Paxil-related lawsuits in more than two dozen U.S. states, says Cindy Hall, a lawyer for the firm. And that was before the U.K. and U.S. regulators issued the warning about children, which she describes as "probably the most significant thing that has ever happened" in the controversy over Paxil and suicide.
How these and other cases play out remains to be seen. But Glaxo increased its provisions for legal and other disputes to ￡507 million in December from ￡227 million in January 2002. The company notes that the provision relates to product liability, as well as antitrust, contract terminations and other matters. It declines to say how much, if any, of that increase relates to Paxil.
The issues being raised with Paxil aren't brand new to the drug industry. Several years after Eli Lilly & Co. introduced Prozac in the late 1980s, the company was sued by patients or their survivors alleging the medicine caused some people to attempt or commit suicide. An advisory panel to the FDA concluded in 1991 that there was "no credible evidence" that Prozac or similar antidepressant drugs cause suicides or violent behavior.
GlaxoSmithKline long has insisted that withdrawal symptoms for Paxil are rare. But it has been adjusting its labels to give patients a clearer picture about what to expect. In May, for instance, it removed language on the U.K. label that said Paxil was "nonaddictive" and amended it to make clearer that patients who stop using the drug can suffer various reactions, including "electric shock" sensations. The U.S. label has mentioned the potential electric-shock sensations since December 2001, according to Glaxo.
At the same time, the company added wording to its U.K. label stating that one of Paxil's side effects could be an increased risk of akathisia, a form of restlessness. Such a label is similar to one that has been carried on its U.S. labels for several years.
And in March, David Healy of the University of Wales College of Medicine published a study in the European journal, Psychotherapy and Psychosomatics, based on clinical trial data provided to the FDA by Glaxo and other companies that make similar drugs. He concluded there was a doubling of the risk of suicides and suicidal acts in adults who took Paxil and similar antidepressants, compared with a placebo.
Glaxo's Dr. Benbow, who has seen the study, says he disagrees with Dr. Healy's methodology and conclusion. "We have got a huge amount of data on the benefit that Paxil/Seroxat has given to millions around the world," says Dr. Benbow. The growing worry about the drug's potential side effects, he adds, "is just the environment we work with at the moment."
Paxil令葛兰素史克投资者面临风险
Paxil是全球医药巨头葛兰素史克(GlaxoSmithKline PLC)生产的最为经典的药物之一，每年带来超过30亿美元的销售额，并帮助数千万的人和抑郁症作战。
但是过去几年围绕在该药物周围已经有所减轻的争议之声可能在未来几个月内再次高涨，这将导致投资于葛兰素史克的投资者在持有该股引发的风险面前踯躅不前。
部分科学家和使用者长期以来一直坚持认为Paxil和相关药物会导致严重的戒断症状，在部分情况下甚至引发暴力和自杀行为。该药在欧洲以Seroxat的名称出售。葛兰素史克和其他制药公司断然否认该指控。葛兰素史克欧洲临床精神病学部门负责人本博(Alastair Benbow)认为没有任何可靠证据显示Paxil会引发自杀或攻击性行为。
但这个问题目前正日益引起监管当局和原告律师的注意，而且这种瞩目程度可能将会增长，这一切导致投资者头脑中逐渐浮现出Paxil未来销售额、葛兰素史克财务状况和公司股价将受何种冲击的问题。
英国监管当局在6月份要求医生不要将Paxil开给儿童，因为有关数据将该药和18岁以下人群的自杀行为联系起来。美国食品和药物管理局(Food and Drug Administration, FDA)立即发出类似的警告。英国监管当局现在正忙于进行Paxil对成年人影响的详尽研究，研究结果定于明年年初发布。另一方面，原告律师正在为起诉葛兰素史克做好进一步准备。
目前尚未进行可能解决Paxil副作用带来的广泛冲击的完全的临床试验。但公司现在可以说是危如累卵。
美林(Merrill Lynch)驻伦敦医药业分析师卡尔弗韦尔(James Culverwell)表示，Paxil很明显对葛兰素史克极为重要。他对该股的评级为买入。（美林发表的葛兰素史克报告指出，其预计在未来3个月内从后者获得或寻求获得投资银行服务收入。）葛兰素史克目前最为担心的是不希望出现大规模法庭起诉案件，因为这将影响该药在成年使用者中的信誉。
在围绕Paxil的争论日益升温的同时，葛兰素史克和包括美国先灵葆雅(Schering-Plough Corp.)及英国阿斯特拉捷利康(AstraZeneca)在内的其他全球医药公司正竭力推出新畅销药，并抵消仿制药竞争带来的预期销售额的大幅下降。去年，葛兰素史克的销售额增长4%至212.1亿英镑，合342亿美元，大幅低于竞争对手辉瑞公司(Pfizer Inc.)12%的增长率。
在过去6个月中，葛兰素史克股价上涨8.5%，而道琼斯欧洲斯托克600指数上涨11%。但是由于市场担心部分药物需要承受来自仿制药日益激烈的竞争，公司股价依旧相对便宜。据Reuters Research称，其股价是过去12个月收益的约16倍，而该行业为21倍。葛兰素史克昨日下跌20便士至11.62英镑。
如果监管当局发现Paxil确实存在导致自杀的问题，葛兰素史克可能会被迫改变Paxil的标识，以反映出在成年病人中使用所产生的潜在自杀倾向风险。这将会导致药方数量减少，并引起销售额下降。美国去年3,000万Paxil药方中的一大部分来自于非精神病医生。如果该药的标识带有自杀警告，他们可能不太愿意建议使用该药。
而且由于和Paxil相关的针对葛兰素史克悬而未决的案件的数量众多，公司在与原告达成代价高昂的和解协议方面承担越来越大的压力。葛兰素史克在英国的最大股东之一Standard Life Investments基金经理威尔逊(John Wilson)表示，诉讼数量十分巨大。尽管该问题尚未水落石出，但还是足以引起投资者的担忧情绪，因为美国是一个热衷于诉讼的社会。
关于Paxil的争论已经在悄悄地升温。两年前，一个怀俄明州的陪审团判定葛兰素史克赔偿640万美元，因为一名男子在服药两天后杀死数名家庭成员后自杀。据原告律师表示，葛兰素史克私下和解了该诉讼，自那以后，公司悄无声息地对其他至少24起诉讼进行了和解。
休斯顿律师事务所Vickery & Waldner的律师维克里(Andy Vickery)表示，公司不能仅仅匆忙赶过来并使用支票簿了事，法院最近针对Paxil的判决已经引发公众对此事件的关注。维克里在怀俄明州的诉讼中代表原告方。维克里表示，该律师事务所最近6个月中已经提起5起独立诉讼，针对的就是Paxil和自杀或攻击性行为的风险。他补充称，Vickery & Waldner在怀俄明州裁决后还与葛兰素史克就12起Paxil诉讼达成和解。葛兰素史克拒绝就和Paxil相关的诉讼或者达成和解的诉讼发表评论。
洛杉矶律师事务所Baum, Hedlund, Aristei, Guilford & Schiavo律师霍尔(Cindy Hall)表示，过去一年中，事务所在全美超过24个州提起和Paxil相关的诉讼。这是在英国和美国监管当局发布有关儿童的警告之前作出的，她认为该警告可能是围绕Paxil和自杀的争议中发生的最为重要的事件。
这些诉讼和其他诉讼如何解决尚不得而知。但葛兰素史克在2002年12月将法律诉讼和其他争议的拨备由1月份的2.27亿英镑提高到5.07亿英镑。公司指出，这批拨备和产品责任、反垄断、合约中止以及其他事项有关。公司拒绝透露如果有Paxil诉讼，那么增加的金额中有多少和其有关。
Paxil引发的问题对于医药行业来说不是什么新话题了。礼来公司(Eli Lilly & Co.)在20世纪80年代末推出Prozac数年之后被病人或者幸存者提起诉讼，指控该药导致部分患者试图自杀或进行自杀。FDA的一个顾问委员会在1991年得出结论称，没有可靠的证据显示Prozac或者类似的治疗抑郁症药物会导致自杀或暴力行为。
葛兰素史克一直坚称，Paxil引发戒断症状是非常罕见的。但公司已经对该药标识作出修改，以便病人更为清晰地得知服药的后果。举个例子，在5月份，公司将在英国的标识上有关Paxil不会致人上瘾的语句去掉，并将其修改为更清晰地告知病人，停止用药可能导致各种反应，其中包括触电般的感觉。葛兰素史克称，自2001年12月起，在美国的标识就提及潜在的触电般的感觉。
此外，公司在英国标识上添加的语句表明，Paxil的一个副作用就是导致烦躁的风险增加。这个说明和美国已经使用数年的说明类似。
今年3月份，威尔士大学医学院(University of Wales College of Medicine)的希利(David Healy)在欧洲《心理疗法和身心医学》(Psychotherapy and Psychosomatics)杂志上发表一份研究报告，该报告是基于葛兰素史克和其他制造类似药物公司提供给FDA的临床试验数据。希利在报告中总结称，服用Paxil和类似抗忧郁剂的成年病患自杀和采取自杀性举动的风险是服用安慰剂的成年病人的两倍。
亲历该研究的葛兰素史克的本博不同意希利的方法和结论。本博表示，公司获得了全世界数千万人从Paxil/Seroxat受益的大量数据。他补充称，对该药潜在副作用的日益增长的担忧情绪不过是公司目前面对的外部环境。
