The One that Got Away
Many people lauded Pfizer's recent decision to halt all clinical trials of its hotly anticipated cholesterol drug torcetrapib as a victory for the drug development process. I'm not so sure.
On the surface it seemed like a good example of how the drug vetting process is supposed to work. When an independent panel recommended ending the trials due to the increased rate of deaths among the torcetrapib group, Pfizer quickly complied - abandoning years of research and hundreds of millions of dollars in investment along the way.
I certainly agree that Pfizer did the right thing in halting the trials. But to me, this situation is more an expose of the drug development process in this country than a success story. This time, the public was saved from a drug disaster like Vioxx or Baycol. But unless the basic rules of the game are changed, it's only a matter of time until something like that happens again - or worse.
Here's the story on torcetrapib. Pfizer had been developing it for years, and it was widely lauded as a future "blockbuster." That's because torcetrapib addressed cholesterol in a novel way: by raising levels of "good" HDL cholesterol. Pfizer's plan was to formulate a new drug combining torcetrapib with Lipitor, their best-selling statin drug, to hit both sides of the cholesterol equation at once.
There were problems with torcetrapib from the beginning. Early trials showed that it raised blood pressure -- not exactly a good thing for a cholesterol drug's target audience. But Pfizer plugged on. When the phase 3 trials began, they recruited 15,000 people to take either a combination torcetrapib/Lipitor drug or Lipitor alone. As the data from that study rolled in, Pfizer announced its intention to file an application with the FDA for approval in 2007. Based on recent FDA fast-track approvals, it probably wouldn't have taken long for the new combo-drug to hit pharmacy shelves.
But then, just one week after that announcement, Pfizer abruptly halted the trial. Seems an independent review board had raised concerns about the rate of deaths emerging from the study. 82 people in the torcetrapib/Lipitor group had died during the trial, compared with just 52 deaths in the group taking Lipitor alone. The board recommended stopping the trials immediately, and Pfizer complied.
This certainly brings some questions to mind. Would Pfizer have acted so quickly if an independent review board wasn't involved? Why wasn't more attention paid to the high blood pressure risk from the beginning? And why was Pfizer messing with Lipitor, its own drug, in the first place? After all, it's the world's best selling drug. If it ain't broke, don't fix it, right?
I don't think I can answer the first two questions, but I'll take a stab at the third. The answer lies in patent protection. Lipitor's patent is due to expire soon, maybe as early as 2010. When that happens, other manufacturers can begin making generic versions of atorvastatin, the generic name for Lipitor. And Pfizer will lose billions of dollars in revenue. In fact, Lipitor is a $13 billion a year drug. This is equal to the gross national product of Yugoslavia, for pete's sake. Get the picture? We're talking about big buck, major moola, massive profits . . . soon to go bye-bye.
Torcetrapib would have been Pfizer's answer to that problem. If they could formulate a new drug combining torcetrapib with atorvastatin, they could receive a new patent for it and enjoy many more years of best-selling bliss. They just had to get the new drug through research, approved by the FDA and awarded a patent before Lipitor's river of cash dried up.
Here's a perfect example of just how much the profit motive is driving the medical establishment in our country today. Just a few days before the torcetrapib debacle was announced, I attended a conference at a major cardiology center, perhaps the premier research institution in the world. Torctrapib was the subject of a full one-hour presentation. The presenter, a noted researcher, was obviously excited about the prospect of a drug that could raise good HDL cholesterol. Historically this has been tough to budge upwards - and many believe that doing so may be a lot more helpful in reducing risk than simply lowering bad LDL cholesterol, which is what drugs like Lipitor do. But instead of focusing on the potential clinical benefits, he went on to note that Wall Street was in effect waiting in the wings with baited breath, ready to capitalize on this new blockbuster. Now you tell me what's wrong with this picture?
This time, the dice favored the public, not the pharmaceutical industry. But I think that is still the exception rather than the rule. Sure, this time a dangerous drug was caught before it came to market. But unless we change the way the system works, it's only a matter of time before another dangerous one gets through. And let's not forget that before this trial was halted, administering torcetrapib resulted in 30 deaths that would have been unlikely had these subjects not received the drug. Apparently this is a cost our society is willing to pay. Hmmmmm . . .food for thought.
