AstraZeneca Drug Should Be Taken Off Market, Lancet Letter SaysJun 24, 2004 | Bloomberg
AstraZeneca Plc's Crestor cholesterol treatment is dangerous and should be removed from the market, a letter written by U.S. consumer watchdog Public Citizen and published in the British medical journal Lancet said.
Sidney Wolfe, the head of Public Citizen's Health Research group, cited data collected both before and after the approval of the drug, which is known as a statin. His concerns focus on reported cases of rhabdomyolysis, a muscle weakness that affects the kidneys and can be fatal, and of other renal toxicity, or damage to that organ.
``The renal toxicity, high rate of cases of rhabdomyolysis compared with other statins, and lack of unique benefit are compelling reasons to remove rosuvastatin from the market before additional patients are injured or killed,'' Wolfe wrote in the London-based Lancet, the world's oldest medical journal.
AstraZeneca said in an e-mailed statement it was surprised that the Lancet chose to publish the letter from the group, ``which is once again critical of Crestor and makes misleading claims based on inappropriate interpretation of data.
``Crestor is well-tolerated and has a safety profile similar to that of other statins when used according to the prescribing information,'' Europe's second-largest drugmaker said. The company also said the medicine gets more people to their bad cholesterol goals than any other currently marketed statin.
Public Citizen, founded by independent U.S. presidential candidate Ralph Nader, asked the U.S. Food and Drug Administration not to approve Crestor and wrote letters in March and May calling for the drug's removal from the market. In October, the Lancet wrote in an editorial that Crestor shouldn't be widely prescribed because the company doesn't have enough research to prove the drug is safe.
AstraZeneca Chief Executive Tom McKillop, 61, is relying on Crestor and new products such as the blood-thinner Exanta to help make up for sinking sales of the company's older ulcer treatment Prilosec. AstraZeneca boosted marketing spending to help Crestor take on Pfizer Inc.'s Lipitor, the world's No. 1 drug.
Prudential analyst Tim Anderson said that while the Lancet letter ``may not really add too much new to the story,'' doctors may pay more attention to the issues because of it.
``The more Crestor safety gets talked about, the more doctors will look for the side effects, and when they look for this, they'll find it,'' he said. ``This is because all statins have side effects. So then it turns into a self-fulfilling prophecy that then generates more safety reports, that then snowballs, etc.''
Merck & Co. and Schering-Plough Corp. are among the companies who may benefit from this, Anderson said. He said that their competing drug, a combination of Merck's Zocor and Schering- Plough's Zetia, called Vytorin, should get FDA approval in a month.
``It has Crestor-like efficacy but without the safety baggage,'' he said.
Some statins, a class of drugs including Crestor and Lipitor, have been linked to rhabdomyolysis. Bayer AG, Germany's second-biggest drug and chemical maker, withdrew its statin Baycol in 2001 after it was linked to fatalities.
AstraZeneca said Crestor has now been taken by almost 2 million patients and that reports of rhabdomyolysis are ``very rare'' and have been seen in fewer than 0.01 percent of patients.
The cases are often associated with inappropriate use, the company said. The incidence of side-effects is similar to that seen in the clinical trials as well as in other currently marketed statins, the company said. The FDA has also said that the occurrence of side-effects is similar to that seen in other statins.
Wolfe cited the presence of blood and proteins in the urine of some patients as cause for concern since this can be a sign of kidney problems.
``By now, the number of reported cases of rhabdomyolysis and renal insufficiency or renal failure is certain to have increased substantially from the number filed by April 13,'' Wolfe said.
AstraZeneca said Crestor is well-tolerated in terms of the kidneys even though protein was found in a small number of patients receiving Crestor, other statins and placebo in the clinical trials.
``This was thoroughly evaluated for Crestor and found to be transient, often resolved on continued treatment and was not predictive of acute or progressive renal disease,'' the company said.
AstraZeneca said a recent study involving over 6,000 patients receiving Crestor for up to 3.8 years showed that kidney function was maintained or tended to improve slightly.
AstraZeneca said it is conducting an ``intensive program'' of post-market introduction monitoring. European regulators have recently carried out a review of the current safety data for the drug, the company said.
Earlier this month, AstraZeneca changed Crestor's European label because of safety concerns. European doctors got letters telling them to start patients on the lowest dose of the drug, to move to the highest dose of Crestor only under ``specialist supervision'' and not to prescribe that dose to patients at high risk of complications at all.
The FDA said at the time it was not proposing a change to the U.S. label, which already mentions the risk factors and many of the recommendations for how to minimize the chances of patients developing muscle weakness complications.
The regulator said it will continue to monitor safety data and wanted to ``re-emphasize to physicians to the importance of carefully following the recommendations in the current product label.''