cancellation of its once-promising cholesterol drug torcetrapib raises questions about whether there was
something wrong with just one drug or with a whole class of experimental compounds.
If it's a class effect, then several companies, including the Swiss giant
, will have some anxious moments as their clinical trials proceed in search of drugs to raise so-called good cholesterol.
So will Pfizer, which has two similar compounds in early-stage studies. A Pfizer spokesman said no decision has been made on these drugs, which, like torcetrapib, are called CETP inhibitors. Pfizer must review research on torcetrapib before it evaluates the others, the spokesman said.
Analysts also speculate that
is testing a CETP inhibitor. Merck hasn't commented, but its executives probably will be quizzed by analysts Wednesday, when the company issues financial guidance, or next week, when it holds its annual meeting.
Roche is expected to make a decision in early 2007 whether to begin the third and last stage of clinical testing for its CETP inhibitor, says Sagient Research Systems, an independent firm which tracks drug development.
Making the jump from Phase 2 to Phase 3 requires a lot more money, a lot more time and a lot more patients than early testing. Pfizer's total R&D bill for torcetrapib is more than $800 million.
Right now, no one is sure about CETP inhibitors. The Food and Drug Administration says it "will continue to work with Pfizer and other sponsors developing molecules in this class of drugs to ensure that appropriate protections are in place to identify any safety signals as early in the development process as possible."
Pfizer was hoping to submit an application for approval to the FDA in mid-2007 based on a series of tests looking at how well the combination pill of torcetrapib and Lipitor reduced artery-clogging plaque when compared with Lipitor alone.
However, a review by
an independent safety monitoring board of a 15,000-patient test sank torcetrapib, after it found that the combination pill had a higher death rate than just Lipitor.
Pfizer will need some time to figure out what happened, and some insight may be gained in March when it analyzes the results of several clinical trials that measure the torcetratpib-Lipitor pill's ability to reduce artery-clogging plaque.
Preliminary results of one test, showed the combination pill did cut bad cholesterol and improve good cholesterol, but it also elevated blood pressure.
When the results were released, Pfizer's chief medical officer, Dr. Joseph Feczko, said he believed the higher blood pressure "will not alter the favorable clinical profile" of torcetrapib in treating cardiovascular disease.
After Pfizer cancelled torcetrapib, Sagient Research Systems said it was "quite concerned that this may be a class effect." The San Diego-based firm based its assessment on information about various experimental drugs and studies of how the body is affected by good and bad cholesterol.
Sagient said Pfizer's experience could force Roche and its partner
to conduct more detailed late-stage clinical trial for the drug R1658. By Sagient's account, Roche has another CETP inhibitor in early clinical testing and so does
is developing a CETP-inhibitor vaccine, now in the second-stage of clinical testing. Avant says it is looking for a partner to help develop and commercialize the product.
Researchers are pursuing good-cholesterol drugs and vaccines because the bad-cholesterol drugs can't do the whole job of helping the heart. Too much bad cholesterol, or low-density lipoprotein, increases the risk of heart attacks, but there's a risk to having too little good cholesterol, or high-density lipoprotein.
Most of the bad-cholesterol-fighters, like Lipitor, belong to the statin class. CETP inhibitors block an enzyme to affect the balance between low-density and high-density lipoproteins. The enzyme carries cholesterol from the good side to the bad side. Thus, a drug or vaccine that blocks this enzyme will improve good cholesterol.
Although many companies are working on good-cholesterol drugs, the Pfizer product attracted the most attention. Torcetrapib was the leading CETP inhibitor, the full name of which is cholesteryl ester transfer protein inhibitor. And Pfizer was relying heavily on it to protect sales of Lipitor from generic competition.
Lipitor loses one U.S. patent in March 2010 and another in June 2011. It accounts for about one-fourth of Pfizer's sales. The company wanted to introduce its Lipitor-torcetrapib pill as early as possible so patients could be switched before generic copies of Lipitor reached the market.
CETP inhibitors act differently than some drugs already on the market. They include Niaspan, an extended-release form of the vitamin niacin, from
, and Tricor, a member of the fibrate drug class, from
Abbott is acquiring Kos.