前兩天的醫藥大新聞應該就是Pfizer 所研發的新心臟病藥torcetrapib 失敗的事了。

從下面的幾則新聞可以看出大家對這個新藥有多少期待了,不管是研究學者、醫生,還是病人。

Doctors leading a global war on heart disease say they are "devastated" by the loss of a new drug they had expected to be an important weapon in the fight against high cholesterol. [USA Today]

The abrupt decision to discontinue torcetrapib was a shocking disappointment for Pfizer and for people who suffer from heart disease. [NYT]

The discovery that an experimental cholesterol drug is dangerous is a major setback for what has been considered one of the most promising new approaches to fighting the nation's leading killer, experts said yesterday. [Washington Post]

But perhaps of greater importance, the development was a disappointment for what many experts consider one of the most important avenues of medical research -- lowering the risk for heart attacks and strokes by boosting levels of high-density lipoprotein, so-called good cholesterol. [Washington Post]

The announcement over the weekend that Pfizer had halted development of a potential blockbuster drug intended to treat heart disease dealt a major blow not only to the company, but to heart patients everywhere. [MSNBC]

心臟病一直都是十大死因之一,目前最成功、最暢銷的心臟病藥是statin,市面上的statin 除了MerckZocor®,還有也是Pfizer 所研發的Lipitor®,而Lipitor®光今年(2005)的銷售額就達到$13兆美金,它的治療方法是降低壞膽固醇(LDL)。這款新藥叫torcetrapib,其實從1990年代初就開始研發了,而且Pfizer 投資了至少$800百萬美金在上面,它之所以被眾所矚目,是因為它的原理和舊藥不同,與其降低壞膽固醇,它的目的則是提高好膽固醇(HDL),感覺起來舊藥是治標,但是新藥可以治本,所以這個方法被認為是心臟病治療上的一大躍進,大家都對新藥有很大的期待,現在出了問題,當然對研究者說是個打擊,醫生病人也都很失望。

The drug, which has been in development since the early 1990s, raises so-called good cholesterol, and cardiologists had hoped it would reduce the buildup of plaques in blood vessels that can cause heart attacks. [NTY]

Scientists had seen torcetrapib as the vanguard of a new wave of medicines that would give physicians new ways to reduce heart disease by raising good cholesterol, following the success of medicines called statins, drugs like Lipitor® that work by inhibiting the production of so-called bad cholesterol. [NYT]

While Lipitor lowers bad cholesterol, which can clog arteries and cause heart attacks and strokes, torcetrapib raised so-called good cholesterol, which carries bad cholesterol out of the blood. [USA Today]

Many researchers have hoped that the next major advance in fighting heart disease would come from a new generation of drugs that boost levels of HDL, which gets the "good" distinction because it clears cholesterol from the blood. [Washington Post]

這裡解釋一下好壞膽固醇。先説膽固醇(cholesterol)本身,膽固醇是組成細胞膜(membrane)的要素之一,另外也用來製造類固醇類(steroid)賀爾蒙和bile acid(不知道中文是什麼)。

好膽固醇的原名是high-density lipoprotein (HDL),它的功能是回收細胞多餘的膽固醇,然後送回肝臟,再送到小腸排掉,因為這樣可以減少血液裡的膽固醇,所以被稱為好膽固醇。

壞膽固醇是low-density lipoprotein (LDL),它的功能是把膽固醇從肝臟送到其他細胞,所以它含有最多的膽固醇,它被稱為壞膽固醇是因為常時間過多的LDL會造成動脈硬化(atherosclerosis)。

新藥已經在臨床實驗三年了,目前是在最後階段了,上個禮拜四Pfizer 才公開表示說,這個藥會是這幾十年來最重要的心臟病藥研發,希望會在2007年拿到FDA的認證,而臨床計畫的最後階段也將在2009年結束。

Just last Thursday, Pfizer's chief executive, Jeffrey B. Kindler, said publicly that the drug could be among the most important new developments for heart disease in decades and that the company hoped to get Food and Drug Administration approval for it in 2007. [NYT]

最後的臨床試驗階段的計畫名稱叫Illuminate,自願者總共有15000名病患,分別於美國、歐洲和澳洲實行。他們把試驗者分成兩組,各7500人,一組是新舊藥混合用,另一組只有用舊藥Lipitor®。Pfizer 這麼做是希望證明新舊藥混合用的效果會比只有用舊藥的效果更好,更能有效降低心臟病發和中風的發生率,沒想到得到的結果卻是相反的。

The halted study, which was conducted in Australia, Europe and the USA, split 15,000 patients into two equal groups, according to Pfizer and the Food and Drug Administration. One group of 7,500 patients took the drug; the other did not. [USA Today]

As is customary, Pfizer had hired a board of independent scientists to monitor the torcetrapib trial, which had been scheduled to end in 2009. The trial, called Illuminate, compared 7,500 patients taking a combination of torcetrapib and Lipitor, Pfizer's best-selling statin, with a similar number of patients taking only Lipitor. [NYT]

Pfizer had hoped the trial would show that people taking the combination pill would be significantly less likely to suffer deaths or heart problems than those taking Lipitor alone. Instead, it showed the opposite. [NYT]

每個月都會有臨床試驗的報告,檢討新藥試驗的結果,然後就在上個禮拜五(12.01)的月報告中,發現只單用舊藥的死了51人,但是新舊藥混合用的病患死亡率高達82人,比只用舊藥的多了31人。所以,即使他們再怎麼看重這個新藥、這個新療法,現在也不得不放棄了。

When the board, at its monthly meeting Friday, counted 82 deaths among the patients who took the drug and 51 deaths in the group who did not take the drug, it called on Pfizer to halt the trial. [USA Today]

The independent monitors called regularly on the first of each month to give a progress report. This time, however, the results stacked up irretrievably against the drug's safety, and the monitors had determined that the numbers could not possibly reverse themselves in torcetrapib's favor. Not only were there 31 more deaths among the people taking torcetrapib, but similar discrepancies were seen in the number of patients suffering heart failure and other problems, giving the company no choice but to stop development. [NYT]

而其實在禮拜六(12.02)的新聞發佈之前,就有專家對torcetrapib 的效用產生懷疑,因為很多病人的血壓升高了,這是很嚴重重的副作用,但是Pfizer 認為這不是問題,提高好膽固醇的效用會蓋過血壓升高的問題。

Earlier research had indicated that the drug increased blood pressure slightly, but it remained unclear whether that was the problem. [Washington Post]

Even before yesterday's announcement, some cardiologists had raised concerns about torcetrapib, noting that the drug raised blood pressure in many patients, a serious side effect for a heart medicine. But Pfizer said those concerns would prove to be unfounded, arguing that torcetrapib's effects on good cholesterol would overwhelm its negative impact on blood pressure. [NYT]

Pfizer 對torcetrapib 的放棄讓人對用提高好膽固醇的方法來治療產生了疑問,有些科學家猜測,可能是藥品使身體製造了會危害人體的其他型態的好膽固醇,不過也可能只是torcetrapib 自己的問題,因為其他利用同樣方法,包括Pfizer 另外兩個和Roche 的一個,還在初步臨床階段的藥,並沒有產生病患血壓升高的問題。不過,當然現在最重要的較就是要找出問題出在哪裡,並且確認提高好膽固醇這個方法到底可不可行。

Pfizer's decision to abandon torcetrapib throws into question the theory that using drugs to raise good cholesterol, known as HDL, will benefit patients. Some scientists worry that the drugs cause the body to produce a form of HDL that may actually be harmful. [NYT]

Now Pfizer, and independent cardiologists, must determine whether torcetrapib's failure indicates that all medicines to raise good cholesterol will have similar problems, or if the problem was specifically related to some defect in torcetrapib. [NYT]

The problem, though, could be specifically related to a defect in torcetrapib, which is known to raise blood pressure, a serious side effect for a heart medicine. Other experimental drugs that raise good cholesterol, including two in very early stage clinical development from Pfizer and another from Roche, do not seem to have similar effects. [NYT]

如果是提高好膽固醇所造成的問題,那...

For people with heart disease, torcetrapib's failure means that progress may be slowing after two decades of substantial advances against the disease. [NYT]

不過,在問題還沒找到答案之前,現在否定這個方法還太早,所以其他利用同樣利用提高好膽固醇這個方法、還在測試階段的藥還是繼續研發,畢竟,要是真的能夠兩種方法雙管齊下的話,對心臟病患來講真的是一件福音。

根據CNN 說,其實niacin -- 也被稱為維他命B3,就有類似torcetrapib 的功能,而且五十年來也一直以維他命的形式販售,之後在1990年代末,Kos Pharmaceuticals 這家公司利用niacin 製造了Niaspan®,一樣是用來提高好膽固醇,且沒有嚴重的危險性,目前正在測試它和Lipitor®合用的效果,只是...

For consumers, the main fallout may be a delay in getting a new medicine that avoids Niaspan's chief side effect -- a hot prickly sensation called flushing that patients hate but that also can be minimized, doctors said. [CNN]

Pifizer 是全世界最大的製藥公司,有106,000位員工,於2005年更有$51兆美金的營業額。這件事對Pfizer是個很大的打擊,因為Lipitor® 將於2010年失去在美國的專利保護,所以想靠torcetrapib 來遞補的,而它其他的新藥還在研發階段,現在torcetrapib失敗的話,在未來的幾年都沒辦法有新藥上市。

For Pfizer, torcetrapib represented a potential blockbuster medicine that could generate several billion dollars in sales annually. Those revenues are crucial for Pfizer, which is fighting to keep its revenues from declining as it loses patent protection on best-selling drugs such as Zoloft, an anti-depressant, and Zithromax, an antibiotic. [NYT]

Finding new medicines is crucial for Pfizer, which in 2004 began to lose monopoly protection on several of its best-selling drugs, opening them to cheap generic competition. In 2010, Pfizer faces the loss of patent protection on Lipitor, the world's top-selling medicine, with $13 billion in annual sales. [NYT]

Pfizer has had difficulty bringing important new drugs to market this decade and its near-term pipeline of new drugs is also thin. [NYT]

現在Pfizer的股票也下跌。

Pfizer, the US drug maker, is set to focus more on strategic acquisitions as investor concern over the failure of its most important pipeline drug, torcetrapib, sent its shares plunging 12 per cent on Monday. [MSNBC]

因為torcetrapib 還在臨床試驗階段,還沒上市,所以並不會像Merck 的Vioxx® 有官司的問題。Vioxx® 曾經是賣的最好的關節炎藥,但是在被證實會致心臟病和中風後就全數下架了。願意接受新藥設測試的病人必須簽waiver,表示他們了解他們所用的藥尚在臨床階段,還沒通過認證。

Because the torcetrapib-related deaths occurred during a clinical trial, before the drug reached the market, Pfizer will not face the product liability lawsuits that have dogged Merck over its painkiller, Vioxx. Merck withdrew Vioxx, a best-selling arthritis drug, after evidence emerged that it could cause heart strokes and heart attacks. Patients in clinical trials must sign waivers confirming that they understand the risks they face when they take unapproved medicines in clinical trials. [NYT]

關於MerckVioxx®,在這篇文章中有解釋。


下面這一段是一定要的啦!

Torcetrapib's failure is disappointing, but developing new drugs is risky and difficult, said Dr. Robert Meyer, director of the agency's office of drug evaluation. "Research is research," Dr. Meyer said. "If you knew the answer, you wouldn't be doing it." [NYT]





新聞內單字

◆ devastate:使…困惑;使…驚愕

◆ setback:逆轉;挫折、失敗

◆ leading killer:這裡指的是心臟病

◆ important avenues of medical research:這裡提出來是因為它用了avenue 這個字。

avenue 除了街、路的意思外,還有方法、途徑的意思。
例:explore every avenue (想盡辦法)
  an aveune to success (成功之道)

◆ blockbuster:something, such as a film or book, that sustains widespread popularity and achieves enormous sales. (引起震撼的人或事)

◆ blow:打擊

例:What a blow!
  It's a great blow to my plan.

◆ vanguard:先鋒

◆ a new wave of medicine

◆ halt:停止。(除了常用的stop,還有這個字可用。)

◆ stack up (idiom):相比;有理

做相比的意思的匙後,常與against 連用。
例:His painting does not stack up against mine.

做有理意思的時候,等於:make sense
例:His report does not stack up.
   = His report does not make sense.

◆ irretrievable:不能恢復的,不能挽救的

◆ in one's favor = in favor of (idiom)

◆ no choice but to ...

◆ throw into question

◆ substantial advances:這裡提出是因為它用substantial,除了significant, important 等等較常用的,還有substantial 可用。

◆ fallout:an incidental result or side effect (發生、產生)

◆ prickly:刺痛的

a prickly sensation (刺痛感)

◆ flush:發紅、泛紅,發熱

◆ revenue:收入、收益;國稅局

在加拿大,退稅的時候會收到Canada Reveune Agency 寄來的支票。

◆ patent:專利

◆ monopoly:專賣、獨占

◆ acquisition:取得、習得

動詞是acquire,這是除了learn 以外還可以用的字喔!
例:acquire knowledge, acquire skills

◆ plunge:突然下降陷入、投入;全神貫注於…

例:plunge into the lake (跳進湖裡)
  plunge into my studies (認真讀書)

口語用法有:take the plunge (idiom) 冒險一試

the shares plunge 12 percent

這裡的shares 是股票的意思,另外常用的字是stock。

◆ dog:這裡是握住、纏住的意思,這裡是只被官司纏身。

the lawsuits dog Merck over its painkiller (Merck因為它的止痛劑事件被官司纏身)

◆ waiver:棄權書





citation from The American Heritage® Dictionary of Idioms. Houghton Mifflin Company, 1992. Answers.com 03 Dec. 2006. (按圖可連結到引用頁面)




新聞原文連結

[CNN] Dual cholesterol therapy still being tested, despite Pfizer failure
[NYT] Pfizer Ends Studies on Drug for Heart Disease
[NYT] End of Drug Trial Is a Big Loss for Pfizer
[Washington Post] Cholesterol Drug's Failure Is a Blow to Researchers
[MSNBC] Deaths Shut Down Heart Drug Trial
[MSNBC] Pfizer's drug failure puts focus on strategic deals
[MSNBC] Drug trial failure pushes Pfizer towards 'cliffs'
[MSNBC] Pfizer ends development of key cholesterol drug








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