Pharmaceutical giant AstraZeneca announced yesterday, Monday 31st March, it was stopping the JUPITER clinical trial on its cholesterol-busting drug Crestor (rosuvastatin calcium) because early findings showed that the drug reduced deaths and risk of heart problems in patients compared to placebo.
A press statement on the company’s website said that the trial’s Steering Committee and also the Independent Data Monitoring Board recommended that JUPITER be stopped early because there was “unequivocal evidence of a reduction in cardiovascular morbidity and mortality amongst patients” who took Crestor compared to patients who took placebo.
JUPITER, which stands for Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin, is taking place at over 1,200 locations in 26 countries. It is part of a global set of Crestor trials called GALAXY, which involves over 64,000 patients in 55 countries.
The trial was designed to find out if Crestor (at a dose of 20 mg a day) would reduce major cardiovascular events in patients with no existing symptoms of cardiovascular disease and low to normal LDL cholesterol (the so-called “bad” cholesterol) but higher levels of C-reactive protein (CRP).
CRP is thought to be a marker of inflammation and increased risk of cardiovascular and other diseases.
The team in charge of the trial is already putting into place shut down procedures whereby over 15,000 patients will be scheduled for final assessments. They will then analyse and publish the results once this final set of data has been collected.
The drug giant hopes the early halt and success of the trial will allow it be offered to millions of new patients.
The success of the JUPITER trial follows last months’ prediction by market research group GfK Market Measures that a competitor drug from Merck & Co, Vytorin, will be dropped by physicians as a first or second line drug.
This was after reports from the ENHANCE trial that showed the drug, which is a combination of the statin simvastatin (Zocor) and ezetimibe (Zetia), was no better than the older simvastatin alone in preventing plaque build up in arteries.
And more recently, a panel of doctors at a cardiology conference in Chicago recommended that Vytorin and Zetia should be tried only after patients have already tried the older drugs, according to reports from Reuters and the Independent. This news sent shares of Merck & Co and Schering-Plough plummetting. The two companies sell the drugs in a joint venture.
Crestor (rosuvastatin) was approved by the US Food and Drug Administration in August 2003 on the basis of several trials lasting at least 6 weeks where the drug was compared to both placebo and other statins. The trials showed that the drug reduced total cholesterol, LDL-cholesterol and triglycerides, and increased HDL-cholesterol (the “good” cholesterol). Patients responded within one to four weeks of starting the drug.
The most frequent side effects of the drug include muscle aches, stomach pain, nausea, constipation, and weakness.
In 2005 the FDA issued an alert stating that rhabdomyolysis (serious muscle damage) had been reported in patients taking Crestor in combination with other statins. The alert stated that (to date) it did not appear that the “risk is greater with Crestor than with other marketed statins”.
However, the label was changed to highlight important information on safe use of Crestor to reduce the risk of myopathy/rhabdomyolysis (serious muscle toxicity), especially at the higher approved dose of 40 mg.
Also in 2005, the FDA refused a citizen petition from public interest group Public Citizen to withdraw Crestor from the market before “additional cases of rhabdomyolysis and kidney damage occur”. The agency made the decision after reviewing a response from AstraZeneca and also repeated the intention to revise the product label.
The FDA’s response was in a detailed letter that explained how in the view of the agency, Crestor was no riskier than other statins on the market and that the risks were detailed in the new labelling.
Crestor is AstraZeneca’s third biggest drug, and is predicted to be the fastest growing.
Sources: FDA, AstraZeneca, Independent, Reuters.
Written by: Catharine Paddock, PhD